Neurotypical?

Applying to Graduate School - Contacting Professors

2012-01-31T12:59:00.001-05:00

When I first started this blog, I wrote some posts about the graduate school application process that are indexed here. Optimistically, I left space for more posts to be written in the future, including one about contacting potential faculty advisers. Ah, to be a first year student again, with so much time for blogging!

Obviously, my grad school application guide has been languishing for a while. But I recently received emails from two different neuroscience graduate school applicants who had questions about contacting faculty at their prospective schools, so I guess it's about time to write this post.

In general, I think it's good to contact faculty before submitting your graduate school applications. This is especially true if you're applying to a program based on the strength of one or two labs -- if those labs aren't taking new students, you might not want to spend the time and fees on that school. I recommend writing to faculty even if you're not committed to a particular lab, though. If you make a good impression via email or phone conversations with a professor, you are more likely to get invited for an interview.

Read on for tips about how to reach out to faculty at potential graduate programs.

Whom Should I Contact?

Most people apply to multiple graduate programs, and I strongly recommend identifying multiple faculty of interest at each school where you plan to apply. That adds up to lots of potential advisers. You don't need to email all of them! Resist the urge to write a form letter and send it out en masse. Professors are smart; they can tell whether you put thought into your message. Plus, they talk to each other, and if they all get identical emails from the same student, they will realize that you're just spamming the entire department.

My advice is to contact professors if you feel like you actually have something to discuss with them. If your previous research experience is similar to their lab's focus, you should be able to have a scholarly conversation about their work. If you're less experienced, but really enthusiastic about their lab, you should be able to convey your reasons for feeling that way. If you're not planning to work in their subfield, but you have a networking reason for contacting them (maybe they collaborate with one of your undergraduate advisers, or you met them at a conference one time, or...), you should be able to remind them of who you are and how you're connected. Don't write to someone if you have nothing to say beyond "I'm applying to the graduate program at [University X] and I really, really want to get in!"

What Should I Say?

Once you've decided to contact a professor at your prospective graduate program, it can be intimidating to craft that initial email. You don't need to sweat it as much as an application essay, but it is important to make a good first impression. I recommend following these guidelines:

1. Be clear and concise. Professors are busy people who receive a ton of email. You want them to be able to read, comprehend, and respond to your message as quickly and easily as possible. Keep your first message down to a few short paragraphs.

2. Identify yourself. As I said above, professors get a ton of email. Make sure they know who you are and why you're writing to them. Give your email an informative subject line and state that you're applying to their graduate program at the beginning of your message. This distinguishes you from undergrads taking their lecture course, collaborators asking for reagents, random eccentrics who stumbled upon the lab website, and any number of other people who might send unsolicited emails.

3. Ask questions. You want to give your potential adviser a reason to respond to you. If you're interested in joining their lab, let them know, and ask whether they have room for new graduate students. If you're interested in learning more about their research, ask specific questions that can be answered in a few sentences (something like, "Can you explain why you used the tail suspension test instead of the forced swim test in your most recent J. Neurosci. paper?" and not something like, "Can you tell me more about your research?"). On the other hand, don't make up a question just for the sake of asking a question -- as I recommended above, you should only be contacting professors if you actually have something to talk about.

4. Be available and accommodating. You're asking this person for a favor; make it easy for them to help you out. It's nice to offer to continue the conversation by phone if they'd prefer that to email, and to offer to send them additional information about you (CV, transcripts, etc.) if they'd like to learn more about your background.

5. Proofread! Run spellcheck. Avoid text-esque abbreviations and emoticons. If you're worried about your writing, ask a friend to read over your message before you send it. In general, you want to come off as intelligent and thoughtful, so try to avoid glaring errors. This isn't as formal as an application essay, but you should still put some effort into it.

Examples

Back in 2007 when I was applying to graduate schools, I wrote the following message to a potential faculty adviser. I would do it differently now, but I wanted to give you a real example, and also to show that even though this email was far from brilliant (marvel at my complete ignorance of neuroendocrinology!), it got a positive response. The professor in question later chatted with me on the phone, and I ended up receiving an offer of admission from this program (although I can't say for sure that my conversation with her had anything to do with it!).

To: [Prof of Interest]
From: Laura Mariani
Subject: Prospective graduate student

Dear [Prof of Interest],

I'm applying to the PhD program in neuroscience at [University] for fall 2008. When I read the research profiles of [University] faculty, I was drawn to your work. I have long been interested in neuroscience, but your research on how the brain interacts with the reproductive system strikes me as a new way to approach the subject, studying more of the whole animal rather than restricting the focus to the brain. My research experience is primarily in cellular/developmental neuroscience, studying mouse models of the developmental disorders Rett syndrome and tuberous sclerosis, but I hope to explore other aspects of neuroscience in graduate school.

I am writing to ask if you are currently accepting new graduate students. If so, I would love to hear more about your work (the [author names] paper listed as being in press on your CV sounded particularly interesting). I would also be happy to tell you more about myself and my background.

Thanks for your time, and I hope to hear from you soon!

Sincerely,
Laura

If I had to do it again today, here's what I would write:

To: [Prof of Interest]
From: Laura Mariani
Subject: Prospective graduate student

Dear [Prof of Interest],

I'm applying to the PhD program in neuroscience at [University] for fall 2008, and I'm especially interested in your lab. My previous research experience is in mouse models of neurodevelopmental disorders (Rett syndrome and tuberous sclerosis), but I am also interested in neuroendocrinology.

I would like to learn more about your work, particularly your recent paper on [hormone stuff]. My experience working with [developmental stuff] taught me [something relevant to endocrinology], so I am especially intrigued by the connections between the endocrine system and neural development. Is this something that I could explore in a rotation with your lab? Are you currently accepting new graduate students?

If you have the time, I would love to discuss this with you by email or by phone (you can reach me at [number]). I am also happy to tell you more about myself and my background, and can provide copies of my CV and transcripts upon request.

Thanks for your time, and I hope to hear from you soon!

Sincerely,
Laura

The revised version doesn't sound as warm and fuzzy because I tried to eliminate "filler" text. It also makes some intelligent connections between my own background and her research. Of course, back in 2007 I didn't know enough to make those kinds of connections -- I've actually learned a few things in grad school! Still, I think it's best to have something specific to talk about, and asking a question about possible rotation projects makes for a better conversation starter than "I would love to hear more about the stuff in this paper."

Both emails are short, focused, and give the professor an easy question to answer in her reply. They also make it clear that I put some thought into the message before sending it, because I comment specifically upon her research program and how it relates to my own interests.

Of course, neither of these examples is a perfect template, and you should let your own interests and priorities shape your interactions with a potential adviser. Even so, I hope that this post makes the process of writing that first email a bit less overwhelming.

Sick Papes

2011-12-16T12:39:00.001-05:00

I have seen the future of science blogging, and it is called Sick Papes.

100% pure gold, guys. Science gold AND comedy gold. The only thing better than seeing a new Sick Papes post on Google Reader is reading Sick Papes posts out loud.

SfN!

2011-11-12T13:09:00.001-05:00

I'm in the Washington Convention Center right now! No time to write a blog post (who knows when there will be...?!) but I'm tweeting up a storm, which is unusual for me but has been fun so far. Stay strong, laptop battery!

More nerdy podcasts for you!

2011-11-02T13:46:00.001-04:00

Way back in 2009, I wrote a post about my favorite science podcasts. Since then I spend less time on the cryostat, so my listening habits have changed. But I still love a good radio story, so I thought I'd share an updated list with you.

Radiolab: Probably everyone already knows about Radiolab. If you're not already listening, you should. It takes a while to get used to the unorthodox audio production style, but I think it's worth sticking it out even if you're initially annoyed by it. The episode entitled Limits of Science was a particular favorite of mine, but they're all pretty interesting. And Jad Abumrad won a MacArthur this year for his work on the show!

The Story Collider: This is my newest discovery, so I haven't listened to that many episodes yet, but it seems promising. It's basically The Moth for science-themed stories. (And if you're not already listening to The Moth, you should be. Certain Moth stories have reduced me to tears on the shuttle bus, they're so powerful.)

Planet Money: OK, this one isn't technically about science. But as a scientist, I find that I often get a "Tell me something I don't know!" kind of attitude when I'm listening to popular science stories. Planet Money takes topics that I don't know much about (economics / finance) and explains them really well. I always come away feeling like I've learned something, even if I don't necessarily agree with their analysis. They work closely with the best radio show ever, aka This American Life. And their blog is fun, too.

Just for fun...

2011-11-02T11:48:00.001-04:00

In the run-up to SfN, things are getting pretty stressful. I'm frantically trying to get those last tidbits of data together for my poster. I'm preparing myself for the onslaught of massive amounts of neuroscience. And, I'm beefing up my immune system with a flu shot (scientists aren't invulnerable to Con Crud!).

During this hectic time, it's nice to have a labmate who is willing to inject some whimsy into the most tedious experiments. We're currently immortalizing mouse embryonic fibroblast cells. These are skin cells taken from mouse embryos that we use for a lot of different cell culture based experiments in our lab. The problem is, primary cells (i.e., cells harvested from a donor animal) don't keep growing forever, so eventually you have to go back and collect more from new mice. In "immortalizing" the cells, we're selecting for cancer-like cells that will keep on dividing and dividing and dividing indefinitely, making our lives easier and requiring the use of fewer mouse embryos in the future.

So, naturally, my labmate and I gave this experiment a Mortal Kombat theme, and named each dish of cells after a different character from the video game. Which line of cells will be the champion?!

I'm personally rooting for Goro. Look at that dude! Talk about an interesting model system.

Why "Neurotypical?"

2011-10-25T16:55:00.001-04:00

I keep thinking that I should write a little bit about the title of my blog, why I chose it, and what "Neurotypical?" means. When I check my Google Analytics stats, "neurotypical" tends to be one of the main search terms that people are using to find me, so I feel a little bad that I've never written about it. But, ultimately, I am not at all an expert in disability studies, neurodiversity activism, or people on the autism spectrum, so I apologize in advance if this piece misrepresents anything about the term or the movement. If you think I messed up, please leave a comment and I would be happy to respond to your feedback.

What does "neurotypical" mean?

Initially, the term "neurotypical" was used to describe any individual who does not have psychological or neurological traits that qualify them for diagnosis with an autism spectrum disorder. It has since been expanded by some to refer to anyone whose neurological development and present neurological state is consistent with what most would consider to be "normal." The use of "neurotypical" instead of "normal" is meant to remove stigma from people with autism and other neurodevelopmental disorders. Creating a dichotomy of "autistic" vs. "normal" puts people with autism into a marked class, while leaving non-autistic people as the default or unmarked class. A label like "neurotypical," on the other hand, is a neutral way to refer to a person based on their neurological state that does not "other" individuals who are in some way atypical. A great discussion of marked and unmarked classes (in the service of explaining why we should use "cissexual/cisgender" to describe people who are not transsexual/transgender) can be found in this post from Speaker for the Diodes.

Some people also use "neurotypical" as part of discussions advocating for neurodiversity. I don't want to put words into anyone's mouth, but as I understand it, the neurodiversity movement is about reframing some traits that are normally classed as pathological, such as atypical communication styles, sensory perception, or emotional regulation abilities. Neurodiversity activists seek to broaden the definition of "healthy" to reflect people whose behaviors might seem different from what we're used to.

For example, here's a video from Amanda Baggs, a woman with autism who is involved in activism within the autism community. Her way of interacting with the world is not typical, but that doesn't mean that she is somehow "less than" a neurotypical person:

In general, I think of terms like "neurotypical" and "neurodiversity" as reminders to check my assumptions and my privilege.

Why did you call your blog "Neurotypical?"

I'll admit it; I was mainly looking for a pun. I'm a neuroscientist and I was trying to think of good "neuro" titles. So, "Neurotypical" popped into my head. But then... I added the question mark!

In part, I was hoping to create some wordplay by writing about my "typical" life as a neuroscience graduate student, with the question mark implying that it may not actually be typical, or that I may not actually know what I am talking about... But, I think "Neurotypical?" also gets at some interesting questions about how we define mental illness and mental health. As someone who studies disorders and diseases of the nervous system, I think it's important to keep in mind the lived experiences of people who have been diagnosed with those disorders as we seek to develop treatments and therapies. It's appealing to me, as a scientist, to reduce everything down to a plain yes/no answer (p < 0.05), or a straightforward biochemical pathway, but nobody's mind is that simple. Do neuroscientists strive to make everyone neurotypical? Is that okay? Do we even know what that would look like?

Are you neurotypical?

That's another interesting question, and kind of personal. I will say that I am generally read as neurotypical; I don't commonly display any behaviors that lead people to think I have a neurological disability or disorder. However, that doesn't mean that I've never had any experience with neurological disorders or mental illness.

One example that I'm comfortable talking about publicly: My first year of graduate school, I suddenly began to experience frequent hypnagogic and hypnopompic hallucinations. These "waking dreams" are vivid hallucinations that occur when you're falling asleep, or shortly after waking. They can be related to other sleep disorders, like narcolepsy or sleep paralysis, but I didn't have those. My experiences with them were very scary, and after they started happening, I was really worried that I might have schizophrenia (hypochondriac neuroscientists are great at self-diagnosis...), or maybe a brain tumor. I saw several doctors who told me that my symptoms were probably due to sleep deprivation. Then I moved into a different apartment, and I realized that my old apartment next to the train tracks had not permitted me to get a decent night's sleep for an entire year. The hallucinations went away almost immediately once I moved out of earshot of the proverbial midnight train to Georgia, and they haven't come back in the past 2.5 years.

Was I neurotypical during that year? Am I now? What about someone who suffers from clinical depression, but keeps it mostly controlled through medication and/or therapy? It's not always easy to define membership in a class, but society always seems to want to put people into nicely labeled categories. (The DSM is a good illustration of this urge...) I don't mean to draw false equivalence between my temporary experience with a sleep disorder and the very real stigma that someone on the autism spectrum experiences every day. I just sometimes wonder about how we define these classes, and how useful those definitions are.

I will also say that although I am read as neurotypical, I have friends and loved ones who are not, and that I feel very strongly about advocating for their rights. Finally, I have noticed that there are lots of people in the neuroscience community who could be called neuro-atypical, or who got into neuroscience because of their experiences with family members and others who have neurological or neurodevelopmental disorders. So, I think this is an area where neuroscientists could stand to learn more from people involved in disability studies scholarship, or social justice activism.

Where can I learn more?

Here are some resources that I've used to inform myself about disability, neurodiversity, and general issues related to social justice and progressive social movements. If you know of others, please leave a comment!

Temple Grandin's books and talks: Temple Grandin is a fairly well known writer who has autism. Her books describe what it was like for her to grow up "different," and how her autism makes her in some ways uniquely qualified for her work.

neurodiversity.org: A fairly comprehensive resource for the neurdiversity movement.

FWD: Feminists with Disabilities for a way forward: On the intersection of gender and disability. The blog has stopped updating, but the archives have some good discussions.

Shakesville: My favorite blog in the progressive blogosphere. Most of the content is written as part of an advanced feminist space and thus might be off-putting for newbies, but this piece about living with depression was really eye-opening for me, in particular.

B.A.N.T.E.R. at SfN

2011-10-06T08:51:00.001-04:00

You know you love neuro-tweetups, even if you don't know what their acronyms mean. (Society for Neuroscience on Twitter: rocking awkward acronyms since "SfN the meh.") Mark your calendars!

(via Dr. Becca)

It's Okay to Be Smart

2011-10-03T13:45:00.001-04:00

If you're not reading It's Okay to Be Smart, a science-themed Tumblr by biology PhD student Joe Hanson, you should get on that. First of all, he blogs like, a million times more often than me. Secondly, he's hilarious. And thirdly, his Tumblr regularly features groovy little bits of science media, like this video about cholesterol.

Scientific American: Cholesterol from Alphachimp Studio Inc. on Vimeo.

I loved the shout-out to anterior/posterior embryonic patterning! Really nicely done.

Absentminded

2011-09-30T11:30:00.001-04:00

Two weeks in a row, I have completely forgotten about lab meeting. I can't even explain what's going on. Either I forget that it's a Thursday, or that we have lab meeting on Thursdays now, or that we have lab meeting in general (like, that lab meeting is a thing that my lab does, which I am expected to attend)... It's getting kind of embarrassing. Let's hope I remember next week, since it'll be my turn to present.

Although I'm apparently experiencing mild cognitive impairment, at least I've gotten some cool data recently. Go, qPCR!

OIST DNC 2011 Write-up

2011-09-12T08:39:00.001-04:00

OIST has put up an article about the Developmental Neurobiology Course (which they shorten to DNC -- it always makes me think "Democratic National Convention") that I attended in July. I'm quoted! There are also some great pictures of the students and labs, including the one pasted below (that's me in the green tank top!).

And, there's a video of us messing around in the lab! I think there should be more science-themed reality TV. Wouldn't you watch a whole hour of people doing experiments (and getting frustrated when they don't work)?

I haven't seen any information about a 2012 DNC, but I will definitely keep you posted about any future neuroscience courses at OIST. The 2011 OISTers are already planning our SfN meetup!

More advice for new grad students

2011-09-08T16:26:00.001-04:00

Today I spotted a couple of links that might be of interest to all the science n00bs in the house: some tips from faculty, to go along with all the advice that I like to spout off around here.

Dr. Free-Ride's Advice for the new grad student

Prof-Like Substance's letter to new grad students

Are you new to grad school? How's it going?

GTPases in the blogosphere!

2011-08-29T14:25:00.001-04:00

During a recent chat with my adviser, she casually mentioned reading about a new study on "the GTPase blog." To which I replied, "There's a GTPase blog?!" I think she was pleased to know more than I did about some aspect of science blogging. So, cheers to my adviser for inspiring this post!

GTPases: From the Bench is a blog by Dr. Anna Delprato that focuses on all things GTPase. Since I'm doing my dissertation on a small G protein (the coolest small G protein... but of course, I'm biased), I'm obviously all over this. In addition to blogging on peer-reviewed research, Dr. Delprato posts information about upcoming conferences that might be of interest to fellow GTPase enthusiasts. You can also follow Dr. Delprato on Twitter (@Gproteins). I admire her dedication to this protein family, and look forward to reading future posts!

On Choosing a Lab

2011-08-26T11:47:00.001-04:00

Yesterday the lovely Ragamuffin shared some of her concerns about choosing lab rotations in this candid post. After composing an epic comment on the subject, I decided that maybe I should turn it into a post over here. The new neuroscience PhD students hit Emory this week (after a highly successful retreat last weekend -- we formed a five level human pyramid, if that gives any indication of how awesome it was) and are starting to think about their rotations, too, so this seems like a good time to write about it.

So, for all the science n00bs out there, I present: Laura's Helpful Hints for Choosing a PhD Lab. As a fourth year student (yiiikes), I've had some time to think about what works for me and what does not. But, I should mention that everyone has different preferences, and that the culture at your institution may make it more or less difficult to find co-mentors, collaborators, etc., so this advice might not fit your individual situation. Also, as I'm sure the more advanced scientists in our midst will mention, I'm not much more than a n00b myself, and may lack the perspective that a more experienced researcher can give you. So don't take my word for it; get lots of feedback.

Helpful Hint #1: Think Outside the Box. A lot of people come into graduate school with several years of experience as an undergraduate researcher or a research technician. They have honed their skills in a few techniques and feel comfortable within their subfield. Knowing this, they are forced to decide whether to stick with the same thing in grad school, or try something new. I would strongly encourage all new grad students to try new things, especially since most PhD programs in the life sciences require several lab rotations. Even if you're 99% sure that you want to study the same thing you've been doing since your undergrad days, it can't hurt to get exposed to new ideas in a rotation. You may find that you love animal behavior studies after doing all your training in cell culture, or that you find electrophysiology really satisfying after years spent on fMRI, or... whatever. You're in graduate school to learn, so it would be a shame to spend your PhD years doing more of the same.

Helpful Hint #2: The Science Almost Doesn't Matter. This is a weird piece of advice, especially in combination with Hint #1, but hear me out. I've encouraged you to try something new, even if it's outside your comfort zone. But what if you try it, and do your PhD in it, and realize that you want to spend your scientific career doing something else? OMG, the pressure!!! Well... chill out, because you don't have to decide right now. In fact, if you want a career in academic research, you're going to need to do postdoctoral research after you get that PhD. Choosing your postdoc lab will be a major decision, because most PIs base their independent research on the training they received as postdocs. But it is generally expected that scientists will switch gears between PhD and postdoctoral research -- you shouldn't do a postdoc focused on the exact same thing as your dissertation. Again, these training experiences are meant to teach you new things, so you're going to need to keep expanding your scientific horizons. Thus, if your PhD lab works on something that you don't really want to study forever... that's okay! You're going to do something else as a postdoc, and that's going to be way more important in shaping your future as an independent investigator. Obviously it's helpful if some of the techniques or concepts can carry over between PhD and postdoc, but you have a lot of freedom to change course. That said: this Hint is called "The Science Almost Doesn't Matter." It matters in that you have to find it interesting. If you're not genuinely curious about the answer to your research questions, it will be tough to keep working on them for the next 5+ years.

Helpful Hint #3: The Training Environment Really, REALLY Matters. The first two Hints were all about how you're here to be trained, damn it, so you should come prepared to learn a bunch of new stuff and not worry too much about the specifics. This Hint is about the "training environment," which is a catchall for your mentor's training style and the overall lab dynamics. As you consider a potential lab, you need to determine whether you're going to be able to effectively learn a bunch of new stuff in this environment. Things to consider: Is the PI a jerk? Are your labmates jerks? Does it bother you to work with jerks, or can you handle it as long as the group keeps churning out awesome data? Obviously, each person has their own definition of "jerk," but for me, it boils down to: if I have really, really screwed something up, can I handle the thought of walking into my PI's office/labmate's cube to come clean about it? Because... you are gonna screw up, eventually, and you need to be able to recover from it without being completely crushed. Other things to consider: Are you being handed a project to complete, or do you have some leeway to develop your own ideas? Do you want to learn more than bench techniques (teaching, grant writing, service, etc.)? Is the PI cool with you spending some of your time on that? Different faculty have different opinions about how much freedom to give their trainees. And, finally, you should consider the really tricky stuff, like how much funding the lab has, whether you'll be expected/required to secure your own funding, and even whether an assistant prof is going to get tenure (and what the plan is if they don't), or whether a more established prof would move the lab elsewhere if they got a job offer. Talking about those last few things can get uncomfortable, but for me, if I don't feel comfortable asking someone about hard topics, I don't really want to work for them. (Although, I did not actually ask my adviser all of these things before I started working for her. I didn't think to ask!) If you don't want to go there with the PI, you can ask other lab members about this stuff (and I recommend doing so anyway, to test the waters and see if everyone's on the same page!).

Helpful Hint #4: Don't Playa Hate; Collaborate. (Runner-up title for this Hint: "Stop, Collaborate and Listen.") Although The Training Environment Really, REALLY Matters, your mentor's lab does not have to be the end-all, be-all of your PhD experience. Maybe you've considered Hints #1-3, and your lab of interest measures up pretty well, but is lacking in a few areas. Maybe the research is interesting, but everything they do is in vitro, and you want training in animal models, too. Maybe the PI is an awesome new assistant professor, and you want to do some experiments that require the resources of a well-funded, well-established lab. If there's another lab at your institution (or a nearby institution) that has what you're looking for, collaboration could be the answer. This is something that I think can vary a lot between universities, but thankfully, I've found Emory to be extremely conducive to collaborations. I know several grad students here with two co-advisers (and one with three!), which can be tricky to navigate but also incredibly helpful for certain projects. While I have only one formal adviser, I have gotten a lot of help from the faculty on my dissertation committee and from other labs in our department. This includes access to equipment and reagents, training in new techniques, and an open door policy for times when I want to bounce ideas off an expert in a topic outside of my adviser's expertise. Your university is full of brilliant, successful scientists, and you should develop relationships with as many of them as you can. This is especially important if you're applying for fellowships and need multiple letters of recommendation -- yes, your DGS can write one for you, but I think a letter makes much more impact when it comes from someone who has really seen you in action as a scientist, whether that's collecting awesome data in their lab or designing clever experiments in their office.

Helpful Hint #5: Communicate. This Hint should be applied in combination with Hints #1-4. You should be very forthcoming about what you're hoping to get out of your PhD experience, what you need from your adviser, what your questions/concerns are, and what you're currently unsure about but hoping to figure out as you go along. Hopefully, your potential adviser will be equally forthcoming about his/her expectations, mentoring style, and resources. Ask about previous grad students, how their projects were chosen and developed over time, and what they're up to now. Assess whether the PI has rules that everyone is expected for follow, or whether they are more flexible about adjusting their training style to the individual. Discuss their philosophy on how your progress will be measured as you work toward your degree, the way work is divided among lab members, the number/type of publications you're expected to write, conferences that you'll attend, classes that you'll take, and anything else that you think might be relevant to your training experience. Ultimately, you're not going to figure everything out during a few early conversations, but you'll get a sense of whether you think the PI is being reasonable or not. Frequent, effective communication is critical in a mentor/trainee relationship: know what is expected of you, do your best to achieve it, and figure out how you'll address the problem if an expectation can't be met.

I think I've spouted off enough for one day. New grad students, I hope you find at least some of this to be helpful. As a neurotic over-thinker, I spent a lot of time agonizing about which grad school to attend, which rotations to do, and which lab to join, and I think it worked out well in the end. But I also think that if I'd made different decisions, I would still have been okay. So, I guess the last Hint is: Just Roll With It. Whatever lab you join, you're going to experience some success and some discouragement and some mind-boggling confusion and some cringe-inducing failure. Welcome to grad school! We'll get through this.

Summer "vacation"

2011-08-17T12:41:00.001-04:00

Oh, hello. I've sort of forgotten to blog much this summer. The last month or so has been a blur, and now the academic year is starting up again. Where did my summer go?!

Well, let's see. In mid-July I left for the Developmental Neurobiology Course at Okinawa Institute of Science and Technology. I admit, I was rather nervous about the trip -- Japan is so far away, and I was going by myself and didn't know what to expect. But I'm so glad that I went. I met a bunch of amazing scientists and learned about cool research that's happening all over the world. Plus, I got to stay on a beautiful island. The student housing was right beside a private beach! I put up a few photos from my trip in this Google Plus album, if you want to check it out. I thoroughly documented the bathroom, because I'm weird. (It was a really nice shower!) I also made a separate album with photos of the jawdroppingly beautiful new OIST research campus. Their plan to fly me out there for a course so that I'd come back and promote the new university is obviously working.

I also think that the experience empowered me. I wasn't sure I'd be able to get over my anxiety about the trip, the food (I'm deathly allergic to most seafood, so Japanese cuisine was a little intimidating -- thankfully, they were very careful with my meals), the science, the big group of strangers all thrown together. Yes, I am neurotic, hi. But while not everything went 100% according to plan, I was fine in the end. And neuroscience teaches us that exposure to anxiogenic experiences during which everything ends up being totally fine makes them less stressful the next time. I didn't even have to take any D-cycloserine to feel better about the thought of future international meetings.

Since returning to the USA on August 1, I've been keeping busy. Last weekend I flew to Boston for a friend's wedding, and I'm heading to another wedding in upstate New York on Labor Day weekend. I've also got the annual Emory Neuroscience Program retreat in north Georgia this Saturday. These social events are super fun, and I always enjoy hanging out with my friends, but I do find myself wishing that they were spread out a bit more. My experiments have been hampered by a month of busy weekends -- not all science can fit into a Monday-Friday schedule. But, I have been getting stuff done.

What kind of stuff? Well, I've been tracking down reagents to use for some tricky experiments that I planned for my dissertation work. I think I finally have a system that will allow me to observe most of my proteins of interest in the same cell at once, which is cool. I've also been helping with experiments for another student's paper (I get authorship, so it's cool with me), training the new grad student, testing new antibodies (I will be thrilled if they work, because if a commercial antibody is available for our lab's favorite protein, we won't have to keep sending our precious rabbit polyclonal to investigators all over the world), and exploring a new side project. I'm especially psyched about the side project, because it means that in the future, when my main project hits a snag (like this recent search for workable reagents), I'll be able to work on something else that's still "mine." Also because the side project was 100% my idea, which makes me feel like a science badass for coming up with an interesting research question by myself. Maybe I can run a lab someday...

Even though I haven't been writing much, I've still been reading my favorite science blogs. I hope everyone out there is gearing up for a great year of research and awesomeness, and I'll try to post more. Oh, and I'll be at SfN in DC this fall, so hit me up if you want to grab a drink with a fellow citizen of the blogosphere...!

Crowdfunded, open source PCR machine now available!

2011-07-08T13:10:00.001-04:00

A couple of months ago, I helped my husband pick out a used microscope (his hobby, collecting and identifying wild mushrooms, sometimes requires 1000X magnification for spores) and joked that I can't get away from biology equipment, even at home. Now it's also possible to kit out our basement laboratory with an inexpensive, open source PCR machine.

I sort of love the idea of backyard biologists using these OpenPCR devices to replicate their BioBricks, but a more likely application would be for science labs at public schools, or medical diagnostic facilities in the developing world. The PCR machines at my lab cost around $10,000 each; OpenPCR costs $512.

Of course, for PCR to work you also need access to DNA primers, nucleotides, and polymerase, which you aren't likely to have lying around the house. Determined citizen scientists will have to track down a source of those materials if they want to get into the PCR game. Still, pretty cool!

(Via BoingBoing.)

Journal of Neuroscience launches "Journal Club"

2011-07-06T11:22:00.001-04:00

My graduate program director just emailed to say that The Journal of Neuroscience is soliciting reviews of recent articles for a new series of features that they call "Journal Club." Trainees (students and postdocs only) are invited to review publications from the past two months, although "inappropriately harsh or glowing reviews will not be considered." Submissions should be no longer than 1500 words.

This should be of special interest to neurobloggers, who are often creating this sort of content anyway for their blogs. (Although, this bit will be tough for bloggers: "Titles should be informative; the Journal discourages word play.")

I'm intrigued, and also a little intimidated. I mean, it's fine for me to spout off about a paper on the internets, but J. Neurosci? That's playing for keeps.

Do you plan to submit any Journal Club reviews?

Hello, readers/classmates!

2011-06-27T16:34:00.001-04:00

Recently, quite a few of my peers have told me that they read this blog, or have read it at some point in the past. And yet, they have never commented, and they seem to show no signs of starting blogs of their own. If you are my classmate, or an anonymous grad student from another program, and you are reading this, please speak up in the comments! Let me know what you like about my posts, what you'd like to see more of, and what factors influence your own decision about whether or not to keep a blog. (Actually, you are welcome to chime in even if you're not a grad student.)

I know that my "applying to grad school" posts are fairly popular, and that prospective grad students for my program have found this blog by searching for info on Emory Neuroscience. What else are my readers interested in? As my work in the lab, in the classroom, and on the Graduate Student Council becomes more demanding of my time, I find myself with less time for blogging. It would be great to hear what you all are looking for when you read this site, so that I can focus my efforts on the stuff that provides the greatest value.

Thanks for reading! I will try to post more this summer, especially about the short course in Japan that I am attending in three weeks. I've also been considering a post about sleep disorders that tries to integrate some science with my personal (and rather freaky) experiences, but as it turns out, writing about articles outside of one's subfield is pretty tough. Please bear with me!

3 Awesome Things

2011-05-25T21:46:00.001-04:00

Here is a list of things that happened today, in order of increasing awesomeness for my science life.

1. I discovered this exquisite protocol for making DNA loading buffer. So nerdy! So useful! (The blog author also has a handy breakdown of life science stipends that I should add to my "applying to grad school" guide...)

2. A new grad student officially joined our lab! Two of my labmates graduated within the past 6 months. Now that there's a newbie, I'm definitely a "senior student." Gulp...

3. OMG, MY GRANT GOT FUNDED! Earlier tonight the American Heart Association sent me an email, CCed to my adviser, saying I could log in to see my application status. My adviser emailed me 5 minutes later to tell me to hurry up and log in so she could hear the result. Then she figured out that she could log in as the application sponsor, read the summary statement, and sent a congratulatory email before I'd had the chance to do anything. It was a flurry of triumphant email activity, let me tell you!

Screenshot!

Just for the record, I'd also like to state that one AHA reviewer specifically praised my "excellent" grades in undergrad as well as grad school. This is in contrast to the person at NIH who cited "mediocre grades at Brandeis" as a weakness on my NRSA application. That one stung. (Probably because I secretly fear it's true... I didn't excel at all of my science classes, way back when. But I got funded anyway!!!eleventy!)

My Students in the News!

2011-05-05T18:43:00.001-04:00

After proctoring and grading my students' final presentations yesterday (fun, but tiring...), I was psyched to see that Emory Magazine has published their four-part feature about the On Recent Discoveries by Emory Researchers (ORDER) program. The web version of the story also includes personal reflections by three of my students.

The main piece, "Trickle-Down Knowledge," focuses on the other section of ORDER, "Blood, Brains, Death and Disease." My section was entitled "Good Germs, Bad Angels, Mutant Mice, and the Secret to Success," bringing together instructors from neuroscience, religion, sociology, and microbiology, but the general concept of the seminar is the same. And all of the student-written pieces come from the class that I helped teach. Here's an excerpt from Makoto Mori's description of ORDER:

Scrolling down a window on my web browser mindlessly to find a course to fill my writing requirement, I came across a class titled Good Germs, Bad Angels, Mutant Mice, and the Secret to Success. Not only did the title grab my attention, but also the fact that the course was cross-registered in eight different disciplines told me it deserved a detailed look. After reading the course description, I learned that this was a course designed to write a research grant proposal while hearing about experiences of researchers from various disciplines. It seemed to fit my interests perfectly. By that time, I was heavily involved in a computational chemistry research lab and was considering research as a component of my career. The only problem was securing a spot in the roster. Even as a senior, I struggled to find a spot and had to wait for one to open up.

So far in the class, we have listened to three PhD candidates in neuroscience, microbiology, and sociology speak to us about their research and life experiences that led them to their research topics. As an undergraduate at Emory, I had opportunities to listen to the lectures of many accomplished researchers, including Nobel laureates, but it was eye-opening to hear about what led the early-career researchers to their projects and accomplishments. Their personal stories made the career in research seem more approachable.

Go see what else Makoto, Zahra, and Billy had to say about our class and their independent research projects! I'm really proud of our students and I'm glad that these three chose to share their enthusiasm about the program.

The Personal is Professional?

2011-04-22T17:44:00.001-04:00

Last summer, when I was developing the curriculum for my ORDER teaching module, I started with a plan that hit the highlights of every biology course I've ever taken and every popular science book I've ever read: cool experiments, wacky phenotypes, stories about the history of science, elegant examples of fundamental concepts. I wanted to borrow from the best in order to supplement the story of my own research. At an early course development meeting, Dr. Lynn listened to my ideas and then gently suggested that I rethink the entire curriculum. He reminded me that I was supposed to design a unique new course. "You are the selling point," he told the Teacher-Scholars. He strongly encouraged all of us to spend class time discussing our personal journeys into academia and our reasons for choosing to study the things that we study. We were positioned as models and mentors for our undergraduate students, and he wanted them to learn about our lives as well as our dissertations.

I was initially resistant to the idea. Why spend time on my undergraduate research experiences when I could be talking about Nobel laureates? But, ultimately, I heeded Dr. Lynn's advice and centered my classes squarely on my thesis and the topics surrounding it (including a day on animal research, during which I told personal stories about how that aspect of my work makes me feel, in addition to more formal discussions of ethics and regulations). It's impossible to say whether my students would have preferred my original plan, but I think they enjoyed the module. And, I've noticed that my own blog reading habits seem to confirm what Dr. Lynn was emphasizing: science is more compelling when scientists feel like real people rather than detached manuscript authors. I love Research Blogging, but I find myself more likely to skim those posts on other blogs, and I've noticed that my own posts attract more comments when I talk about my personal experiences than when I review an article.

Sometimes I skip writing here because I don't feel like I have time to compose a well-researched scholarly analysis on whatever topic has popped into my head. I feel pressure to meet a high standard because I blog under my real name and I want future professional contacts who read this to think of me as a Serious Scientist. Especially after learning that my adviser regularly includes links to this blog when she writes me letters of recommendation! (The realization left me feeling both proud and terrified, which seems to be the optimal emotional state for PIs to evoke in their trainees.)

But, what I value most about science blogs is the community, and how fellow bloggers give me a window into the lives of my peers and near-peer role models. If that's what I'm getting out of it, perhaps I should put more in, and write more of that sort of content.

I hope to follow through with more self-reflective writing in the future, although the thought still weirds me out a little. I am debating whether or not to write a series of posts on my experiences with some neurologically-relevant phenomena (I swear this is not code for recreational drug use). Many of my favorite bloggers who write about the intersection of science with family responsibilities, personal crises, and social factors are pseudonymous. Given my... "nymity?"... I'd appreciate thoughts on the line where community-building crosses into over-sharing.

Hunger Hormone Enhances Sense of Smell

2011-04-15T12:30:00.001-04:00

The smell of coffee wafting through the air this morning may have inspired me to write about this Journal of Neuroscience paper from Dr. Jenny Tong and colleagues at the University of Cincinnatti. Their work showed the effects of the appetite-stimulating hormone ghrelin on the olfactory system. It seems only logical that hunger should have effects on food-seeking behavior, including the detection of food smells. This study sheds light on the mechanisms through which ghrelin modulates olfactory processing in both rats and humans.

But first, a little background on the wonders of the olfactory system. I am not a systems or behavioral neuroscientist, but if I was, I would totally study olfaction. The olfactory system appeals to my interests in cellular, molecular, and developmental neuroscience. We all have tons of olfactory receptor neurons (ORNs), each of which somehow expresses only a single odorant receptor gene (out of approximately 1000, in humans). And each ORN, depending on which receptor it expresses, sends its axon into the olfactory bulb, where it joins up with the axons of all other ORNs expressing that receptor in a beautiful structure called a glomerulus. To get a sense of how cool that is, observe this image from Feinstein and Mombaerts (2004) showing mouse ORNs expressing an olfactory receptor called M71, labelled in blue:

Check it out: neurons in the olfactory epithelium inside the nose (left side of the image) are exposed to the air, which allows them to bind to inhaled odorant molecules. They send their axons through a bone (the ethmoid) in olfactory nerve fibers that converge on the appropriate glomerulus (near the upper right corner). Glomeruli occur in stereotyped locations, residing in the same part of the olfactory bulb in every individual. What's not shown here is that there are ~2000 distinct glomeruli in the bulb, and ORNs always find the right ones. The olfactory system, in short, is really cool.

Studying olfaction doesn't just provide a great excuse to say words like "glomerulus" (Latin for "a small ball;" from the same root as "conglomerate," as in to roll a bunch of disparate things into a ball). The system is a minor miracle of carefully regulated gene expression, axon pathfinding, and tricky neural coding used to translate the activation of ORNs into a downright Proustian experience. Perhaps that's why the first people to figure some of this stuff out received a Nobel Prize.

But enough of my olfactory fangirling. Back to Dr. Tong and her colleagues, who were interested in how this elegant system functions after the glomeruli have formed and the animal is out there in the world, sniffing for food. Specifically, they wanted to know how changes in nutritional state affect olfaction. Do hungry animals differ from satiated animals in their food-seeking olfactory processes? To test this, the researchers specifically measured two factors important for functional olfaction: sniffing behavior and olfactory detection thresholds (that is, how sensitive are the ORNs to very low levels of an odorant?). They found that ghrelin enhances both.

Neuroendocrinologists have identified a bunch of hormones and neuropeptides that contribute to sensations of hunger and satiety, but the main "hunger hormone" is ghrelin. Ghrelin is produced in the stomach and circulates throughout the body to stimulate feelings of hunger and increase food intake. (After learning about ghrelin in our first year systems neuroscience course, my classmates and I frequently invoked it at lunch time. "Are you ghrelin?" "Yeah, I'm ghrelin like a felon!" ... it was a timely joke in 2008, okay?) Interestingly, ghrelin receptors are found on facial motor neurons involved in sniffing movements, which implies that this hormone may regulate food-seeking behavior in part by inducing animals to start sniffing for their next meal.

For this study, the researchers first showed that ghrelin receptors are found not only in "sniff neurons" in the facial motor nuclei, but also in the olfactory bulb itself. This provides a mechanism through which ghrelin can modulate not just sniffing but also olfactory sensitivity. They confirmed that ghrelin increases olfactory sensitivity in rats by measuring whether the rats could detect very low levels of an odor in their drinking water. After rats were conditioned to avoid an odor (odorized water was paired with a drug that made the rats feel sick), Dr. Tong and colleagues measured how much the rats drank from a bottle of pure water versus a bottle containing very low concentrations of the odor. Rats that were given an infusion of ghrelin avoided the odorized water, even when the odor was diluted by a factor of 10^-10. Untreated rats still drank from the most dilute odorized water bottles, indicating that they were unable to detect the odor at such low concentrations. This implies that ghrelin binding to olfactory brain regions lowers the threshold of odor detection -- in other words, 'hungry' animals are more sensitive to smells. There does seem to be a maximum level of ghrelin-mediated olfactory sensitivity, however: rats that fasted overnight were more sensitive to odors than rats that had recently eaten, but treating the fasting rats with ghrelin did not further improve their ability to detect very weak odors.

Dr. Tong et al. also showed that ghrelin increased exploratory sniffing in rats "using a video-based, fully automated behavior analysis system (HomeCageScan, Clever Sys) that recognizes, records, and quantifies the movement of the nose tip while the animal was either fully or partially reared in a home-cage environment." (That is not even close to the funniest/weirdest sentence from an olfaction paper, either. My favorite is from Stowers et al., 2002: "The time required to discover a hidden cookie (latency) is similar in mutant and wild-type mice," followed by a graph of "cookie latency." Cookie latency is a standard measure in the olfactory behavior literature. This particular paper contains other LOLs, though -- it's about how mice that lack a certain ion channel lose the ability to distinguish between males and females, and thus display indiscriminate mating behavior. End immature parenthetical.)

The researchers also measured sniffing behavior in humans. Here, I think, is where the Materials and Methods section of the paper becomes really awesome:

Sniffing behavior was evaluated using the sniff magnitude test (SMT) as described previously. Briefly, a canister was placed ∼2 cm beneath the nose, and subjects were instructed to take a single, natural sniff as would be taken when sampling a perfume or food. The stimuli used were as follows: nonodorized air, baby power odor (baby power fragrance oil, 50% dilution, The Good Scents Co.), banana odor (isoamyl acetate, 1% dilution, Sigma-Aldrich), and tomato odor and rosemary chicken odor (both undiluted, formulated by Givaudan). Three sniffing trials were collected for each odorant and six for air. A specialized software program identified the initiation of sniffing, recorded sniff pressure at 10 ms intervals, summed sniff pressures, and measured each sniff's duration during a 5 s sampling period. The sum of the pressure values was defined as the sniff magnitude. The subjects were also asked to rate the pleasantness of the odors immediately after each trial using a visual analog scale [scores ranging from −5 (slightly unpleasant) to 15 (best smell ever)]. The order of stimulus presentation was randomized. The average sniff magnitude and odor pleasantness ratings were used for data analysis.

Subjects were given the SMT after an infusion of saline or of varying levels of ghrelin. The result was that the cumulative sniff magnitude was significantly increased by all doses of ghrelin, but not by saline. Ghrelin treatment had no significant effect on the pleasantness rating of any odor, however. (I wonder why the scale doesn't go below -5? Artificial banana odor sounds more than "slightly unpleasant" to me. Certainly nowhere near "best smell ever.")

In sum, ghrelin increases an olfactory food-seeking behavior (sniffing) in both rats and humans, as well as olfactory sensitivity in rats. No measurements of odor detection threshold were made in humans, however, which I found a bit disappointing. It would be unethical to induce conditioned odor aversions in humans, but it seems like it should be possible to ask people to discriminate between scented and unscented samples, or between two different odors at very low concentrations. Perhaps it was too difficult to design that study, or to recruit enough participants interested in receiving i.v. ghrelin infusions. (Perhaps a "ghrelin like a felon" TV commercial would be helpful?)

One surprising result of this study was that ghrelin levels had no effect on sniffing for food odors vs. non-food orders, nor on how participants rated the pleasantness of individual odors. Other studies have shown that feelings of hunger increase human preferences for food odors, but these results imply that those effects are not due specifically to the action of ghrelin. Rather, ghrelin seems to upregulate food-seeking behaviors like sniffing without necessarily affecting the hedonic value (pleasantness) of food-related cues. Perhaps other appetite and satiety hormones, like orexin and leptin, are involved in food odor preferences in hungry individuals. This just goes to show that even the most basic biological drives (everyone eats!) aren't as simple as we might expect.

References

Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, Julliard K, Woods SC, Horvath TL, Sleeman MM, D'Alessio D, Obici S, Frank R, & Tschöp MH (2011). Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. Journal of Neuroscience, 31 (15), 5841-5846 PMID: 21490225

Feinstein P, & Mombaerts P (2004). A contextual model for axonal sorting into glomeruli in the mouse olfactory system. Cell, 117 (6), 817-31 PMID: 15186781

Stowers L, Holy TE, Meister M, Dulac C, & Koentges G (2002). Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science, 295 (5559), 1493-500 PMID: 11823606

OIST Developmental Neurobiology Short Course

2011-04-06T20:34:00.001-04:00

I'm very pleased to announce that I will be spending two weeks of my summer in Okinawa, Japan to participate in the Okinawa Institute of Science and Technology's Developmental Neurobiology Course. Given how much fun I had at last summer's Gordon Conference on Neural Development, I'm sure I'll return with a head full of ideas for exciting new experiments, just in time to have them shot down at my next committee meeting. No, but seriously, it sounds really cool. And as a bonus, all my travel expenses are covered by OIST.

I have to admit that I am a little hesitant about traveling to a far-off location for several weeks by myself. It's not like I'll be wandering around lost in a foreign country -- science conferences and courses are very structured, and all of our sight-seeing will be supervised. But I've never traveled to a meeting without classmates or labmates before, and I've never traveled internationally for work at all. My nervousness has reminded me that I'm privileged to live in close proximity to most major scientific conferences. I don't envy the jet-lagged folks from around the world at SfN each year, and now I'll get to walk a mile in their shoes.

Despite my qualms about the travel, I'm excited about the course. I'm especially looking forward to the lectures and labs on invertebrate development, since most of my research experience is in mammalian systems. I have wondered if I should try to do a postdoc using flies or worms instead of mice, but my only experience with Drosophila was in sophomore year bio lab, and I've never even seen a C. elegans nematode in person. The course will provide some hands-on experience and a lot of interaction with experts in these systems, so I hope to come away with a better idea of what it would be like to work in an invertebrate lab.

In general I'm left a little stunned that someone wants to give me an all-expense-paid science vacation. I'm pulling a 13-hour work day today (not typical; it's a long story) and haven't had a work-free weekend in quite a while, but I have to say that the perks of being a grad student are pretty cool.

Wicked Burn, PhD

2011-04-04T16:50:00.001-04:00

Me (giving lab meeting): I'm not sure if this protein motif is important or not. It seems conserved, but then again, if you stare at the amino acid sequence long enough, you start to see all kinds of stuff.
Labmate: Like the face of Jesus?
Me: I've never looked for Jesus in a protein sequence. But I did BLAST my own name once, to look for MARIANI peptides.
Adviser: ...Wow.
Me: Bet you didn't know I was that much of a dork, huh?
Adviser: Oh, no. I knew you were that much of a dork.

Next Steps for Undergraduate Researchers

2011-02-21T12:15:00.000-05:00

In my last post, I wrote about the undergraduate teaching I've been doing this year, and about my attempts to guide interested students along the path to careers in research. The other ORDER Teacher-Scholars and I serve as role models by talking about our personal journeys to graduate school alongside our research findings. In addition, we try to design lectures and classroom activities that will be helpful to our students outside the context of this course. We also provide group and individual mentoring for students pursuing their own research interests.

I've been thinking a lot about where our students might go after completing our seminar. How can we help them apply what they've learned? Can they aspire to something more than just an 'A' on their transcripts? Can our class help them add a line or two to their CVs? In that vein, here are some of the goals that I've encouraged my students to pursue.

Undergraduate Research

This seems a little redundant, given the title of my post, but not all of our students are currently engaged in research on campus. Last semester, the students were all first years, so they hadn't the opportunity to get involved in research yet. By structuring our course around our own research process and requiring the freshmen to design and carry out their own projects, we tried to empower them to think of themselves as researchers and scholars.

Since the end of the fall semester, I've had five students (out of 18) contact me with questions about finding a lab. I've written letters of recommendation for summer research programs, encouraged students to apply for Emory's SIRE and SURE fellowships, provided lists of Emory faculty working in various fields, and even helped one student join my adviser's lab. I'm very pleased with this outcome. Although the majority of the credit surely goes to the high-achieving students themselves, I like to think that the mentoring we provided had at least some impact on students seeking out research opportunities.

Education and Outreach

Each student in the ORDER seminar formulates a group or individual research project. In addition to writing papers about their findings, the students are required to integrate a "creative component" into presentations of their work. Last semester, students made videos, wrote and performed original songs (with costumes and choreography!), and acted out skits to convey the key points of their research to an audience of their peers. We also encouraged them to think about how they might convey their work to other audiences, like K-12 students or the general public. In class, I've promoted programs like Brain Awareness Week, where students can use their creative presentation skills to engage kids in discussions of neuroscience. I tell my students that this kind of outreach is important for scientists who depend upon public interest to fund their work, and that volunteering in an area related to your field also looks good on your CV.

Last semester's students will soon be participating in an event for high schoolers who are considering an Emory education. They will present their original research projects and answer questions from the visiting students. I haven't heard whether any of them have been motivated to volunteer off campus as a result of the class, but maybe they'll be more inclined to do so next year, when they're allowed to have cars!

Publication

Most scientists scoff at the thought of publishing a paper after only a semester's worth of work on a project. (Although, I do know a few lucky grad students who were able to publish the results of their rotation projects!) For an undergraduate, though, a semester-long research project is a substantial achievement, and many of our students are interested in learning how to publish their results. This semester, one student also asked me about publishing a lengthy review-style article that he wrote for a previous class.

I identified a couple of journals in my field that would be appropriate venues for this kind of work. The Journal of Young Investigators publishes scientific research articles, reviews, editorials, and features. They also sponsor a snazzy virtual poster presentation contest:

For students particularly interested in neuroscience, there's also Impulse, an undergraduate journal of neuroscience.

Both of these journals feature peer review by other undergraduates under the supervision of faculty sponsors. While most submissions are eventually accepted, students submitting to the journals will still go through a dialogue with the editors and typically make a round or two of revisions. It's a good introduction to the publication process, and it provides another way for students to get credit for the high level of work that we ask of them in class.

Funding

This semester, we're having our upper-level undergraduates write mock funding proposals. Many of the science students have shown an interest in NSF Graduate Research Fellowships or NIH Intramural Research Training Awards. We hope that by asking our students to design research projects and write them up in a grant-style format (including a background and significance section, a research strategy and timeline, and a personal statement), we can prepare them to actually submit these sorts of proposals.

When I was an undergraduate, I didn't even know that these funding sources existed. Learning about them will definitely give our students an advantage. But, grant writing is hard, and it has been challenging for me to mentor a diverse group of students who are all at different stages in the research process. Some have already spent years working on a project in an Emory lab, while others aren't sure what kind of graduate program interests them the most (a few haven't even picked an undergraduate major!). I'm trying to set reasonable expectations for my students, given that many of them have never attempted anything like this before. But, I also want to make sure they understand that in order to get a proposal funded, they will have to work hard, revise a lot of drafts, and read more than a handful of primary sources.

I hope that I'll be able to report back later this year with an update about what our students have achieved! I've been putting a lot of effort into teaching (to my adviser's occasional chagrin...), and perhaps my ambitious goals are a result of the newbie's rose-colored glasses. But, I'm having fun. Last week I met with a small group of students to talk about their grant proposals. When class time had run out, several of them stayed late to continue our conversation. One told me that she didn't want to leave because this was her favorite class. I never get that kind of feedback from mice in the lab!

Undergraduate Researchers: What's Their Next Step?

2011-02-12T16:22:00.001-05:00

I've written before about my participation in a teaching fellowship called On Recent Discoveries by Emory Researchers (ORDER), but I wanted to reflect a little more on my experiences working with the talented undergraduates in these classes. Because I want to preserve my students' privacy/anonymity, I'll be discussing them and their research projects in fairly general terms. But, I will say that I have been consistently impressed with my students. I'm privileged to be a mentor for them as they pursue their academic goals.

The cool thing about ORDER is that it's interdisciplinary. Last fall, ORDER fellows (we're actually called "Teacher-Scholars" in official ORDER materials) taught a first year seminar for the incoming class of INSPIRE students. This meant that most of our class had an interest in the sciences, and some had even pursued scientific research experiences in high school. Even so, when they were asked to devise independent research projects as part of the course, the students created and tested hypotheses that spanned the social sciences as well as the biological sciences. Several of them also decided to take classes in the social sciences and humanities after completing our course. This was at least in part because of the research shared by Teacher-Scholars from the Department of Sociology and the Graduate Division of Religion, as well as the students' own inquiries into non-science topics.

This semester, my ORDER cohort is teaching a similar course for upper-level undergraduates in multiple disciplines. (The seminar is cross-listed in: Chemistry, Biology, Neurobiology and Behavior, Physics, Psychology, Religion, Sociology, and Theatre Arts!) Our students are more advanced than last semester's freshmen. Most are currently pursuing research and/or have decided that they are interested in postgraduate education. Many of them have been supported up until this point by the awesome undergraduate research programs at Emory. They are so awesome, in fact, that there are YouTube videos documenting them!

Programs like Scholarly Inquiry and Research at Emory (SIRE) support undergrads working in all majors, not just the sciences. I know of many universities that have scientific research opportunities for students, either during the summer or the academic year, but it seems less common for disciplines like sociology. So, I think it's really cool that Emory is supporting research by students like Kristen Clayton:

By providing a pool of funds dedicated to undergraduate researchers, SIRE allows all students to access a research experience. This is crucial — some faculty might not be able or willing to pay an undergrad from their own funds, and many students don't have the financial luxury of taking an unpaid position. SIRE also provides training in communication skills, research ethics, and other important areas that students will need to master for a successful career.

In working with these students (not just SIRE fellows, although I think the presence of the program encourages more Emory undergrads to get involved in research in general), I've been thinking more about how the other Teacher-Scholars and I can prepare them to take the next step in their research careers. How can we help them use their Emory experiences as a jumping-off point for their graduate and professional education? Pondering this has forced me to think outside my own areas of expertise — I'm responsible for mentoring neuroscientists, but also chemists, sociologists, humanists, artists, and students who still haven't made up their minds about what they want to do.

In my next post, I'll share a couple of the ideas that I've come up with (in collaboration with other members of the ORDER program). In the mean time, I'd be interested in hearing ideas from the peanut gallery of the academic blogosphere. How would you approach this kind of class? What do you wish you'd known when you were preparing to graduate from college, and how can I convey that information to my students?

On Self-Promotion

2011-01-27T11:31:00.001-05:00

There's been some buzz around the blogosphere lately about the Science Online '11 panel on "Perils of blogging as a woman under a real name." Especially interesting to me (and a lot of other people!) was Ed Yong's comment that while he receives lots of inquiries from male bloggers asking him to promote their work, he has never received a single message of the sort from a woman. Prof. Kate Clancy wrote about this at her blog, and there's some great discussion in the comments, too. Dr. Becca spun off from the discussion to talk about her own self-promotion tour, which sounds pretty awesome.

These posts got me thinking about ways in which I promote myself and my work, or fail to. For example: Back in 2008, when I was applying to graduate schools, I was still working as a technician at Children's Hospital Boston. Because of the hospital's affiliation with Harvard Medical School, all kinds of fabulous scientists came to visit and give seminars on a regular basis. It's standard for students and postdocs to have lunch with visiting speakers at most institutions, including Children's. Technicians are less likely to be invited, though. Then one day, a Famous Guy from a Really Good University came to give a talk. I was really excited, because I had decided to apply to Really Good University's Neuroscience Graduate Program, and I was interested in Famous Guy's lab. So my PI said that I should go to the student/postdoc lunch with Famous Guy and introduce myself.

Well. The time came for lunch, and I sat there with my sandwich and cookie at a huge conference room table with like 15 trainees and Famous Guy. I had never been to one of these lunches before and I felt very intimidated. I thought the grad students and postdocs were much smarter than me, and that they probably had cooler projects, and were more successful, and I had no idea what to say to Famous Guy about my own project, or my graduate school dreams. And, forget about asking a question about his research -- I was sure that any question I had would do nothing but reveal how ignorant I was about his field.

At one point, Famous Guy asked everyone at the table to go around in a circle to introduce themselves and summarize their research (also fairly standard at these lunches). As I listened to everyone else, I started to feel more comfortable -- I might have been clueless about Famous Guy's work, but at least I could describe what I'd been doing for the past 18 months and sound halfway intelligent. I waited for my turn, thinking about a punchy elevator pitch for my coolest result.

So, the person on my left finished talking, and then there was a bit of discussion around the table as Famous Guy asked questions and other people jumped in to answer them or ask their own questions. I waited for a lull so that I could get back to the introduction game and have my say. And then, the woman on my right took the opportunity to jump into the discussion. She said "I want to ask you about something, because my project is focused on [stuff], and I think it really relates to your work on [other stuff], so what do you think of [idea]?"

Famous Guy was really interested in her idea, and they started this rapid conversation about her project and stuff related to her project that lasted for the last remaining minutes of the lunch. She totally skipped me! I was so flummoxed; I had no idea what to do. Everyone else had talked about their science while I just ate a sandwich.

At the time, I projected all of my resentment onto the trainee sitting to my right, who had seized the moment and gotten Famous Guy's attention. I felt like this had to be an intentional slight against me, and that she was being rude by not giving me a perfect moment of silence in which I could give my spiel. But now I realize that being heard at a group discussion requires that kind of assertiveness, and I know she wasn't trying to steamroll me. She had to kind of steamroll everybody, or else she wouldn't get a chance to share her idea. (Looking back, I also think that they had way too many trainees in the room for that lunch -- things are much more pleasant when there like five trainees, and everyone has time to gab about the weather or whatever in addition to the science talk.)

Anyway, I didn't get into Really Good Graduate Program. I didn't even get an interview. But I got interviews at five other graduate programs, and was accepted to all of them. During one-on-one interviews, I felt very comfortable talking about my project at Children's and my other accomplishments. I was able to get over my shyness, and people responded positively to what I had to say, which increased my confidence.

I've continued to get better at the game. This week I had lunch with two different seminar speakers at Emory. Now that I've had more training, I'm able to see how my work relates to the speaker's work, most of the time, and ask intelligent questions. I'm also no longer afraid to say, "I hadn't even heard of [thing you study] until I looked it up on PubMed yesterday, but is it possible that [insert wacky idea related to my project]...?" And, I no longer resent it when another student or postdoc monopolizes the speaker's attention. Instead, I wait for a pause, and then say something like, "Well, I guess I should introduce myself: I'm Laura..." (Or, if I've already had my turn, I'll say, "Hey, I don't think [other person at lunch] talked about her work yet... did I miss it?")

I really enjoy these opportunities to meet visiting scientists and talk about my research with them. The trainee lunches are nice because they give me a chance to ask my stupid questions in front of a smaller group, since I'm still usually too scared to raise my hand at seminars in the big auditorium. Obviously I need to get over this. I also need to work on putting myself out there at conferences, where the Famous Guy types tend to walk around surrounded by a herd of admirers. I have not yet mastered the technique of getting their attention in a crowd, so if they don't visit my poster, I'm kinda out of luck.

My blog is another story. What's the equivalent of the trainee lunch (i.e., self-promotion training wheels) for science bloggers?

Bad Project

2011-01-23T10:23:00.001-05:00

This video has gone viral amongst Emory neuroscience students on Facebook, so I thought I'd share it here. I love the costume design!

Contains swearing, so might be NSFW, depending on your work.

Long Time No See!

2011-01-14T22:13:00.001-05:00

Hello, blogosphere! It's been a while.

I spent the past few months dealing with the busiest semester of my life. Here's a little summary of what I've been up to:

I submitted my first grant ever! After submitting for the August deadline, my NRSA was scored, but the percentile was not good enough to be funded. Still, not bad for a first try. I've taken the comments and used them to whip my grant into shape for resubmission. In fact, I'm revising it right now for the American Heart Association's predoctoral fellowship. (I know what you're thinking -- why is a neuroscientist applying for funds from the American Heart Association? They also fund research on stroke, and on "related fundamental problems" in basic science.)

I went to a sweet Gordon conference! The Neural Development one, at Salve Regina College up in Rhode Island. I also used the meeting as an excuse to go visit a bunch of friends in Boston. The whole trip was a blast. I definitely want to go back for the 2012 meeting, and I may try hit another Gordon conference this summer. Emory just sprang for $650/year in professional development funds for every single graduate student, so I hope to attend a small conference and SfN this year.

I taught my first class as an instructor (as opposed to a TA)! My first semester as an ORDER Teacher-Scholar was great. I teamed up with three other grad students to teach a seminar about our research on diverse topics. The freshmen in our class learned all about neuroscience, microbiology, sociology, and ancient apocalyptic literature. I was blown away by how talented Emory students are -- the students' research projects were creative and interesting, and their papers were actually fun to grade. This spring I'll be teaching a modified version of the same course to upper-level students. I'm looking forward to revising my lesson plans to keep the things that worked and tweak the things that didn't. (One thing that worked: I had the students score abstracts in a mock study section! Clearly, I had grant writing on the brain.)

I finished my coursework! After a scheduling issue last spring, I had to take an elective in the fall to complete all of my required credits. I ended up in a seminar about ion channels. Ion channels aren't really related to my research, but reading X-ray crystallography papers made me feel smart (and also, at times, really dumb).

I mentored a student in the lab! She's still working with me, actually, and doing a great job on her project. In the process of training her, I've gained new respect for all of the people who trained me, and a little bit of new respect for myself, when I consider just how much I've learned over the past eight years in various labs. It's a lot to teach! But it's been a lot of fun thus far.

I PASSED MY QUALIFYING EXAMS! Yeah, that deserves all caps. Be glad I'm not using the < blink > tag. I'm a PhD candidate now! My entire cohort passed quals on the first try, because that's how hard we rock.

And, last but certainly not least, I got married on January 2! (I remain Ms. Mariani, for those who may be wondering if my Blogspot address and Twitter handle will need to change.)

I definitely would not have made it through 2010 without a supportive partner to start dinner, fold laundry, buy groceries, pick me up from classes that ended after the bus stopped running, and listen to me vent when I was stressed to the breaking point. While I would not necessarily recommend planning a wedding during one's craziest year of grad school, I'm thrilled to start the new semester as a newlywed.

Most of Atlanta has been snowed in for the past week (!), and I'm enjoying the lull before going back to academic life. Here's hoping that 2011 is a bit more laid back than 2010, so I can return to regular blogging.

Benchfly Helps Me Learn and LOL

2010-06-07T18:28:00.001-04:00

Today I discovered Benchfly, a Web 2.0 science hub centered around instructional videos for scientists both in and out of the lab. Current protocols range from time-saving tips for minipreps (that eppi rack trick was news to me) to how to make an Old-Fashioned (I bet Dr. Becca will approve). The good folks at Benchfly also run a blog and, of course, Facebook and Twitter pages, so you can follow their musings about life as a lab rat.

But I have to say, what really won me over was how funny some of the videos are. This one, for example, speaks profoundly to anyone who's ever done immunofluorescent staining:

And this one really resonated with me, because four-letter words and violence are the best way to deal with equipment failure:

Benchfly seems to overlap a bit with the Journal of Visualized Experiments in the sense that both focus on video protocols. But, JoVE seems to be working under an older model of protocol sharing. According to my PI, who has been approached by JoVE in the past due to the "highly visual" nature of our research, JoVE can send a video crew to your lab to film experiments and help with all of the production work. The resulting videos aren't free, however -- you need a JoVE subscription to view most of their protocols. I don't know how many people/institutions do pay for a subscription, but I know Emory's library did not subscribe, last time I checked.

Benchfly, on the other hand, is crowd-sourced and free. Many of the video protocols are made by their staff, but other users are able to submit them as well. Not sure if they plan to implement a pay subscription later, but I hope not. I enjoy the humorous and informal nature of these video protocols. To me, the difference between JoVE and Benchfly feels like the difference between reading the Materials and Methods section of a journal article versus reading someone's lab notebook, complete with hand-written smiley faces and "WTF?!" notes.

Coffee and Cigarettes: Good for Your Brain?

2010-05-17T13:22:00.001-04:00

A recent paper by Kien Trinh et al. in the Journal of Neuroscience suggests that coffee and tobacco have a protective effect in two fruit fly models of Parkinson's disease. Surprisingly, these effects do not depend on the obvious "active ingredients" of these substances (i.e., caffeine and nicotine), but occur through some alternative mechanism.

The connection between coffee consumption and lower risk of Parkinson's disease has been known for a while. When I was applying for research assistant positions in 2006, one lab that interviewed me was studying the effects of caffeine in a mouse model of Parkinson's. Scientists began investigating this link after epidemiological studies based on large numbers of human patients showed that people who regularly consume coffee (and, to a lesser extent, other caffeinated beverages) are not diagnosed with Parkinson's disease as often as those who turn their noses up at the beverage of the gods (Elbaz et al., 2007). One interpretation of this trend is that something in coffee either ameliorates the symptoms of Parkinson's, or protects against the underlying cause of the disease -- death of the dopamine neurons in the substantia nigra of the brain. (The other possible interpretation is that some unknown factor, aka a "lurking variable," makes people both more likely to drink coffee and less likely to get Parkinson's.) Indeed, animal studies have already shown that giving mice caffeine and similar drugs protects against degeneration and death of their dopamine neurons in one model of Parkinson's disease (Kalda et al., 2006; Quik et al., 2008). Similar epidemiological studies indicate that tobacco users also have reduced risk of Parkinson's.

The authors of this paper wanted to test the effects of coffee and tobacco in another model organism, the fruit fly. For their study, they used two kinds of genetically-manipulated flies: one that overproduces the human alpha synuclein protein in dopamine neurons, and one with a mutation in the parkin gene. Alpha synuclein is the primary component of Lewy bodies, the abnormal protein aggregates seen in the neurons of Parkinson's patients. Mutations in the alpha synuclein gene (which is called SNCA) are known to cause some rare forms of familial Parkinson's disease. Similarly, mutations in parkin are linked to an inherited early-onset form of Parkinson's disease. Both types of flies exhibit degeneration and death of their dopamine neurons, making them a good model of the pathology of human Parkinson's disease. Additionally, parkin mutant flies exhibit abnormal climbing behavior and a reduced lifespan, similar to the movement disorders and other symptoms seen in human Parkinsonian patients.

Trinh et al. used lifespan, climbing behavior, and number of dopamine neurons in the brain as a measure of disease severity in mutant flies. The researchers wanted to test whether any of these characteristics were affected by exposure to coffee or tobacco.

In one of the more whimsical Materials and Methods sections I've read, they explain:

Coffee extracts were prepared using Starbucks House blend (Starbucks Corporation) or Tully House blend (Tully Corporation) for regular coffee and Starbucks decaffeinated House blend for decaffeinated coffee (Starbucks Corporation). Tobacco extracts were made using Eve light (Liggett) or Skoal Smokeless tobacco (Skoal) for regular tobacco and Quest2 (Vector Tobacco) for nicotine-free tobacco. Extracts were prepared by adding 18.4 g of ground coffee and 50 mg of dried tobacco separately to 100 ml of water and boiling for 30 min. The extracts were ... added to standard cornmeal–molasses fly food at varying concentrations.

After feeding coffee and tobacco extracts to the mutant flies, Trinh and colleagues dissected their brains to count their dopamine neurons. These were compared to the brains of mutant flies that did not receive the extracts. They observed that both parkin and SNCA mutant flies given coffee or tobacco extracts had more dopamine neurons than those given regular fly food. These results were significantly different, although upon perusing the graphs I noted that untreated flies had about 8-9 dopamine neurons in the relevant brain region, while flies given tobacco or coffee had 9-10. We're talking about a difference of one cell, here. (Although, if you put it another way, it's a difference of 10-12%!)

The authors then repeated this experiment on other flies, but replaced the coffee or nicotine extracts in the fly food with pure caffeine or pure nicotine. This time, they could not detect a difference in the number of dopamine cells between untreated flies of either genotype and flies treated with caffeine or nicotine. Another experiment using extracts from decaffeinated coffee and nicotine-free tobacco did show a significant effect, however. This led Trinh et al. to deduce that the protective effect of coffee and tobacco on the flies' dopamine neurons was not due to the action of caffeine or nicotine.

The researchers tested the effects of coffee and tobacco on mutant flies with other methods, as well. They fed decaffeinated coffee and nicotine-free tobacco extracts to parkin mutant flies and measured their lifespan and climbing ability. The mutant flies given coffee and tobacco were better climbers than untreated mutant flies -- they were able to climb a distance of 10 cm within 30 seconds in about 50% of climbing trials, as compared to untreated flies, who only completed the climb about 40% of the time. The treated flies also lived longer: although most mutant flies (treated and untreated) died by the age of 40 days, a few coffee- and tobacco-treated flies survived to 50 and 55 days, while none of the untreated flies did.

Trinh et al. went on to verify that coffee and tobacco extracts (regular and caffeine-/nicotine-free) significantly reduced neuronal degeneration in a cell culture model. Neuron cultures from mutant flies that overproduce alpha synuclein do not have very many dopamine cells; the extracts significantly increased the number of dopamine cells seen in such cultures. In fact, based on the graphs, the alpha synuclein cultures treated with coffee or tobacco seemed to have more dopamine cells than neuron cultures from normal flies! The researchers didn't explicitly test the effects of coffee and tobacco on normal neurons, however, so I can't say whether this difference is significant.

Finally, the authors suggest a mechanism for how coffee and tobacco might protect against neuronal degeneration in Parkinson's disease. They suggest that compounds in coffee and tobacco (including a molecule called cafestol) act on a transcription factor called Nrf2. Nrf2 normally activates genes that lead to increased production of an antioxidant called glutathione. Trinh and colleagues treated mutant flies with cafestol and saw results reminiscent of coffee and tobacco extract treatment. They also showed that coffee and tobacco lose their neuroprotective effects in mutant flies if they block the action of Nrf2, suggesting that the extracts are indeed acting in an Nrf2-dependent manner.

This paper leaves us with several questions. Perhaps the most relevant one is, why does decaffeinated coffee improve dopamine neuron numbers, climbing behavior, and survival in mutant flies, when other studies in mice implicate caffeine as the factor responsible for coffee's neuroprotective effects? There are several important differences between the fly and mouse disease models to consider. Aside from the obvious fact that mice are not flies (and thus, the two species differ in many aspects of their brain chemistry), the Parkinsonian mice used to study the effects of caffeine were generated by giving genetically normal mice a toxin that kills dopamine neurons. The fly model used in this study, however, is based on genetic mutations. Therefore, it's possible that caffeine is useful for protecting dopamine neurons from toxins, whereas other compounds in coffee and tobacco (like cafestol) can correct intrinsic problems that arise from mutations in a dopamine cell. The obvious next step is to test the effects of caffeine and decaffeinated coffee on genetic mouse models of Parksinon's disease, to see if the fly results can be repeated in mammals.

Of course, neither animal model of Parkinson's disease (toxins or mutations) is perfect. The vast majority of human Parkinson's cases are idiopathic, meaning that we don't know what caused the disease in these patients. Their symptoms cannot currently be explained by exposure to toxins or inherited mutations in genes like SNCA and parkin. Therefore, it's not clear whether caffeine or Nrf2-related factors like cafestol are responsible for the epidemiological trends seen between coffee or tobacco consumption and Parkinson's disease. At this point, scientists are still searching for what factor(s) might be shared between idiopathic cases of Parkinson's disease, in order to develop effective methods for preventing and treating the disease in these cases. In the mean time, though, studies like this one continue to expose new molecular pathways that might be relevant in neurodegenerative disease. And, of course, this particular paper helps justify my coffee habit, for which I am grateful.

References

Elbaz A., & Tranchant C. (2007) Epidemiologic studies of environmental exposures in Parkinson's disease. Journal of the Neurological Sciences 262: 37–44 DOI:10.1016/j.jns.2007.06.024

Kalda A., Yua L., Oztas E., & Chen J.F. (2006) Novel neuroprotection by caffeine and adenosine A2A receptor antagonists in animal models of Parkinson's disease. Journal of the Neurological Sciences 248(1-2): 9–15 DOI:10.1016/j.jns.2006.05.003

Quik M., O'Leary K., & Tanner C.M. (2008) Nicotine and Parkinson's disease: implications for therapy. Movement Disorders 23: 1641–1652 DOI:10.1002/mds.21900

Trinh, K., Andrews, L., Krause, J., Hanak, T., Lee, D., Gelb, M., & Pallanck, L. (2010). Decaffeinated Coffee and Nicotine-Free Tobacco Provide Neuroprotection in Drosophila Models of Parkinson's Disease through an NRF2-Dependent Mechanism Journal of Neuroscience, 30 (16), 5525-5532 DOI: 10.1523/JNEUROSCI.4777-09.2010

Using Mendeley for Long-Distance Mentoring

2010-04-29T17:13:00.001-04:00

Last week I received an email from a student who's applying for one of Emory's undergraduate research programs. The SIRE Research Partner Program matches undergrads with faculty working in their areas of interest, teaches them research and communication skills through a series of educational workshops, and provides funding or class credit for their hours as a research assistant. This prospective SIRE trainee wants to work with my adviser. Once she joins the lab, I'll be training her in various laboratory techniques and providing some supervision for her day-to-day activities. I want to do more teaching and research mentoring, so I'm really looking forward to working with her.

In the meantime, she's asked me for a list of papers that she should read to help familiarize herself with the work we do in our lab. The simplest thing would be to email her some citations or PDFs, but I wanted a more interactive way to bring her up to speed. Papers are always easier to manage once you've talked them over at journal club, and it seems unrealistic to expect a rising college sophomore to understand all of the details in these papers without any help. Ideally, we'd get together regularly to discuss the papers and how they relate to her project, but that isn't possible while she's spending the summer with her family in another state.

So, I decided to create a shared collection with her on Mendeley. Using the free Mendeley Desktop software, I can add papers from my own reference library to a collection that I've named "Summer Reading." (This collection is not public; only the two of us have access to it.) My student can read the papers from home on her own copy of Mendeley, allowing her to familiarize herself with a reference manager (an important research skill!) and communicate with me about her reading list.

I attached PDFs to each reference in our shared collection. Then, I used Mendeley's annotation capabilities to highlight areas of particular interest for her project, and left a few comments in the "Tags & Notes" field to help her focus on the most important points in the paper. These annotations are shared along with the PDF, so my student can follow along easily while she's reading the paper at her computer. I've also encouraged her to add her own annotations as she goes along.

After she's had a chance to read, highlight, and add notes to a paper, she can sync Mendeley Desktop and upload the annotations that she made. They'll show up on my computer the next time I sync my reference library. I encouraged her to include any questions that she has about the papers in these annotations. I think the "sticky notes" will be especially useful for this -- instead of having to quote a paper at length, or refer to "page 7, paragraph 2" in a message, she can stick a digital note right next to the relevant portion of the text. I can continue editing the PDF to respond to her questions, and we can go back and forth as needed.

I did have a little trouble while I was setting this up. This is my first time using shared collections on Mendeley, and some of the documentation on their FAQ is a bit sparse, so I had to go by trial and error. The most important point: In order to collaboratively annotate PDFs, all members of a shared collection must open the collection in Mendeley Desktop, click the "Edit Settings" button, and check the boxes for "Upload attached files to shared collection" and "Download attached files from shared collection." Otherwise, PDFs attached to the references won't show up, and annotations made to those PDFs won't be shared with other members of the collection. These are turned off by default, and until I stumbled onto the relevant menu options, I had no idea how to make attached files show up in the collection. I made one of my labmates join a shared collection with me, then ran back and forth between our two computers a few times until I got it working. It seems obvious now, but I thought I'd mention the solution in case other people who want to try this are as clueless as I am.

We'll see how this works over the summer. If written communication proves insufficient for our needs, I may suggest a few Skype chats to talk things over in real time. Anyone else have suggestions for long-distance collaboration / educational tools?

Troubleshooting Gateway Cloning

2010-04-18T20:51:00.001-04:00

After struggling with a particularly annoying problem in the lab, I finally got my experiment to work this weekend! When I crowed about this to my partner, he told me that whenever he figures out the solution to a tricky problem in his line of work, he blogs about it, for the sake of others who might have the same issue. I did my share of Googling while troubleshooting my experiments and didn't find a solution, so I thought this was worth blogging about. The following will make very little sense if you don't do molecular cloning.

I spent almost three months trying to clone my DNA sequence of interest into a mammalian expression vector using Invitrogen's Gateway Cloning system. Things were going smoothly for a while -- I made a pENTR entry clone, chose a pDEST destination vector, did the LR clonase reaction according to the instructions in the kit, did a diagnostic restriction digest to confirm that my plasmid had the expected sequence, and then... I couldn't maxi-prep the plasmid. This was my first time using the Gateway system, so I expected to hit some bumps in the protocol, but I've been doing maxi preps (with Qiagen kits -- regular and the HiSpeed) for years. So, I felt pretty stupid when my experiment broke down at that point. I got my plasmid out of a mini prep, but failed to recover the plasmid after inoculating a maxi-sized culture with the same exact construct in the same exact competent cells. What the hell?

As I grew increasingly frustrated, my adviser had the outlandish idea to repeat the experiment with good controls. So I did. I used every control I could think of. I transformed, mini-prepped, and maxi-prepped: my entry vector, a known entry vector with a similar sequence that we had lying around the lab, my expression vector, a similar expression vector from the lab, and the empty entry vector. I also repeated the LR clonase reaction with my plasmids and with other Gateway plasmids we had on hand.

I could get maxi prep DNA from everything except LR reaction products (i.e., any sequence of interest flipped from pENTR into pDEST through attR/attL recombination). For some reason, the expression clones would grow in mini preps, and some sort of antibiotic-resistant bacteria would still grow in my maxi cultures, but I would get abysmal plasmid DNA yield from the maxi preps. I tried growing my bacteria at a lower temperature over a longer amount of time, which sometimes helps bacteria keep larger plasmids (my plasmid of interest was about 9 Kb), but that didn't help. I bought fresh new LR clonase enzyme, but that didn't help either.

Eventually, senior lab members remembered someone having a similar problem a few years ago. They thought that the issue was finally resolved by making fresh pDEST vector by culturing bacteria containing the empty vector from the original glycerol stock. I thought that made no sense, but it was easy enough to dig the glycerol stocks out of the freezer, grow up some cells, and prep the DNA. So I did. I then used the newly made pDEST DNA to repeat the LR clonase reaction with my entry clones, transformed the LR product, and grew up some bacteria for a maxi prep.

And... it worked!

I don't know why it worked. I guess somehow, after being stored in the freezer for a while and going through enough freeze-thaw cycles, the pDEST DNA that we had stockpiled went bad. It worked well enough to take up the insert from my pENTR clones and grow in competent cells in a 2 mL culture, but then it petered out when I tried to grow a 150 mL culture of the same cells. So, if you are having a similar problem, I say to you: find your old glycerol stocks. My labmates say that the last time they had this problem, transforming the plasmid back into some ccdB-tolerant cells (the pDEST vector we used contains the ccdB suicide gene) and re-prepping from them also worked, but I can't verify that.

Next up: transfecting my expression vector into some mammalian cells to see what happens! (Also known as: the experiment that I actually care about, which I was sure I would have gotten to by now...!)

Rebecca Skloot's Visit a Success!

2010-03-30T14:38:00.001-04:00

After many months of planning and 197 event-related emails (according to a quick search of my inbox this morning), Emory welcomed Rebecca Skloot to our campus yesterday. Our plans for her visit came together almost perfectly. There were about 50 people at our student seminar on The Immortal Life of Henrietta Lacks, and about 200 in the audience at Rebecca's talk in Cannon Chapel. Many participants took the time to tell me how much they enjoyed reading the book, discussing the story, and listening to Rebecca speak. I'm glad to know that others found the events to be as rewarding as I did.

When I originally invited Rebecca to come to Emory, I imagined a reading and book signing similar to the ones I've attended in the past (at lovely shops like Brookline Booksmith and Back Pages Books). This event surpassed my expectations. The Immortal Life of Henrietta Lacks connects with people on an intimate, emotional level, and inspires readers to ask themselves hard questions about life and death, love and loss, right and wrong. Rebecca presents years of meticulous research with an engaging writing style to educate her audience without patronizing or preaching. She describes the members of the Lacks family, their history, and her own relationships with them in a way that reminds us that these characters are not just characters, but real people with complex personalities and tragically human problems. After a reflective introduction by Emory's Senior Vice Provost, Ozzie Harris, Rebecca's straightforward narrative left the large crowd completely rapt at her reading.

We were also incredibly fortunate to have Dr. Roland Pattillo (if you've read the book, you may recognize the name) in attendance last night, as well as two relatives of the Lacks family: Jessica Holmes, a doctoral candidate at Emory's Woodruff School of Nursing, and her mother, Imogene. Several other members of the audience had roots in Clover, VA (the home town of the Lacks family) or at Johns Hopkins University (where Henrietta Lacks was treated for her cancer, and where the HeLa cell line originated). For me, meeting all of these wonderful people in person brought the story of HeLa and the Lacks family home for me in a powerful way that is hard to describe. After Rebecca's talk, some of the event organizers chatted with these special guests next to the bookseller's table until the long line of autograph-seekers had gone by. Hugs were exchanged.

As a scientist, I've known about HeLa for a long time, and I was even told a brief version of the Henrietta Lacks story in my college biology lab, but I'd never felt personally connected to this chapter of scientific history. Reading The Immortal Life of Henrietta Lacks made me imagine how I'd feel if I learned that part of my father, who died of cancer when I was 17, was alive in a lab somewhere. It made me look up the origins of other immortalized cell lines that I have used, like SH-SY5Y cells. (Those cells were derived from a bone marrow sample from an anonymous four-year-old girl with metastatic neuroblastoma -- "After progressive debilitation and continued growth of tumor, the patient died in January 1971.") It made me re-evaluate every sarcastic conversation I've had with my fellow grad students about our required ethics training seminars. (Suggestion to ethics seminar organizers: Put this book on the syllabus.)

But, all that is just my opinion. What made yesterday so rewarding was hearing that others have responded to Rebecca's book in similar ways, and in different, equally important ways. Our "book club" seminar yesterday afternoon included faculty from four disciplines (Dr. Michelle Lampl from Anthropology, Dr. Ora Strickland from the School of Nursing, Dr. Paula Vertino from the Winship Cancer Institute, and Dr. Dorothy Roberts, visiting Emory from Northwestern University's School of Law) sharing their expert knowledge and helping us examine the story of Henrietta Lacks from multiple perspectives. We also invited undergraduates, medical students, nursing students, law students, business students, theology students, and graduate students from Anthropology, Biological and Biomedical Sciences, Comparative Literature, Educational Studies, the Institute of Liberal Arts, Sociology, and Women's Studies to join the conversation, each with their own unique point of view and response to the story. The Immortal Life of Henrietta Lacks is a truly interdisciplinary work that inspired us to reach out to our colleagues in different corners of the academy, to learn from each other. Several people said that this seminar was the most truly interdisciplinary event they'd attended since coming to Emory, and that they would love more opportunities to have these kinds of discussions. (In response to these comments, we informed people about other interdisciplinary activities on campus -- though most of them don't give away free books.)

In summation, I'm very proud to say that I was a part of the events that took place here yesterday. With the support of dozens of Emory faculty, administrators, staff, and students, my colleagues and I were able to do something that I feel is supremely important: We opened minds. We brought people together. We affirmed essential human principles. Based on the emails I've gotten today, we changed at least a few lives.

Thanks for reading, for listening, and for helping.

Rebecca Skloot at Emory on March 29!

2010-03-16T13:30:00.001-04:00

I have some exciting news to report today. After months of planning, I am pleased to announce that Rebecca Skloot will be visiting Emory on Monday, March 29, to discuss her bestselling book The Immortal Life of Henrietta Lacks. She'll be speaking at Emory's Cannon Chapel at 7:00 PM, with a book-signing to follow. This event is free and open to the public. We hope to draw a large crowd, so come on down!

I've had a lot of help putting this event together. Rebecca and her publicist have been great about dealing with the unique demands of a grass-roots book tour, and I appreciate their patience as I've flailed around trying to set this up. I'm also forever indebted to a fellow graduate student, David Ritchie, and to the Assistant Dean of Student Progress and Special Programs at Emory's Laney Graduate School, Dr. Virginia Shadron. VA and Dave stepped up when I came to a Graduate Student Council meeting begging for money and assistance, and they really came through for me. Also, Quinn Eastman, a science writer at Emory, tracked me down via this blog and helped organize and promote Rebecca's talk.

We're fortunate enough to have received financial and administrative support from twelve different offices and departments across the university (so far!), proving that if everyone chips in a little bit, you can make something awesome happen.

Finally, this event would not have come to be without the science blogosphere. I found out about Rebecca's book tour through her blog, and left a comment expressing interest in bringing her to Emory way back in the day. Since then, The Immortal Life... has been featured on the cover of Publisher's Weekly and praised by the likes of NPR, the New York Times, ABC World News, Oprah Magazine, and many others. It's currently #5 on the New York Times Hard Cover Best Seller list for hardcover nonfiction (and has gone as high as #2 in recent weeks!). So, I'm glad I got in on the ground floor of this tour, because the hype has totally exploded! To me, this is one more example of how web-based media provide unique communication and networking opportunities for scientists and science enthusiasts. That's something I hope to explore further in the future (I'm applying for a teaching fellowship to do this with Emory undergrads... stay tuned for an update on that later!).

Mendeley: My New Favorite Reference Manager

2010-02-27T13:40:00.001-05:00

This semester, I'm writing my first grant. My graduate program includes a course called Hypothesis Design and Scientific Writing, in which students work with faculty and peers to prepare an application for an NIH National Research Service Award (NRSA). My grant is coming along, but I still have lots of work to do. My goal is to submit the final product to the NIH sometime this summer. If I'm lucky, they'll decide to fund my proposal, and I'll receive additional support for my dissertation research. (Emory Neuroscience students have about a 60% success rate at getting their NRSAs funded, so I have high hopes!)

This grant has required a lot of background reading. I spend my free time in the lab scouring PubMed for relevant articles that will support my hypothesis. I've therefore been required to come up with a system for keeping track of all these papers. After trying several options, I've found Mendeley to be the most useful.

Mendeley shares features with other research bibliography tools like Papers, Zotero, and Quosa, but in general I find it to be more suited to my needs. The Mendeley Desktop program works "like iTunes for research papers." It keeps track of citation information and allows users to sort their references by category. Mendeley stands out, however, by linking the desktop client to web-based services that make my life much easier.

The Mendeley web importer is absolutely dreamy. If I'm looking at an article on Pubmed or on a journal website, I can use the "Import to Mendeley" bookmarklet in Firefox or Safari to automatically add the citation to my Mendeley database. Doing this prompts the user to enter tags and notes about the article right in the browser, which will be carried over to the desktop client as well. This is similar to Zotero's browser-centric approach to reference management, but I prefer Mendeley's approach. The Mendeley bookmarklet is unobtrusive -- it opens a small pop-up window or a new tab every time I add a reference. When I tried Zotero, I didn't like the way that it generated weird browser panes at the bottom of whatever page I was reading when I added a new reference. Adding tags to a Mendeley citation takes just a few seconds and doesn't interrupt my browsing experience -- I just close the tab/pop-up when I'm done. When I want to pore through my references in more detail, I use Mendeley Desktop, which as a dedicated application feels 'separate' from my browser, and makes it easier for me to focus on the articles. I find the interplay between Mendeley Desktop and the web importer to be just right -- this comes in contrast to Quosa, for example, which tries to integrate web-based search into the reference manager, but feels clunky and awkward. I already know how to use PubMed in my browser; I don't want my citation manager to make me learn a different way to search (even though Quosa's automated searches are pretty nifty).

Mendeley also automatically backs up all of my citation information to the cloud. I can log into my Mendeley account from any computer, and if that computer has Mendeley Desktop installed, I can sync the desktop client to my web account by entering my email address and password. The Mendeley account preserves all of a user's citations, as well as custom user-generated notes and tags. So, I can easily access all of my references and notes from home, even if I originally found all of the articles at lab. This is both convenient and smart -- in addition to making my life easier when I need to take a project home with me, this automatically creates two backups of my reference database: one at home, one in the cloud. If my lab computer dies (unlikely for now, since my PI just bought me a shiny new iMac, but it's always a risk), I won't lose my precious papers.

One aspect of Mendeley that doesn't thrill me is the social networking component. My Mendeley account includes a user profile, and I've been encouraged to add 'contacts' who also use Mendeley. I can see how this might be useful for sharing papers between lab members or collaborators, but I don't find it necessary. When my PI wants to send me a paper or an EndNote library, she can just email me the files. And I have some concerns about security -- sharing Mendeley databases with the wrong person might reveal too much about a sensitive line of research. I favor a more open-source approach to science, but many scientists are terrified of being scooped, and would prefer to guard their lab secrets more stringently. Even so, it's quite possible to use Mendeley's other services without creating a list of contacts. And Mendeley uses personalized account info to do a few nifty tricks, like displaying the most popular papers for Biological Sciences, based on which citations were imported by the most Biological Sciences users on a given day. Users can also add papers to the "My Publications" category in their profile, and track the popularity of their own articles on Mendeley.

The web-based features are my primary reason for preferring Mendeley over other options, but I also like Mendeley Desktop a lot. I can attach a PDF to a Mendeley citation, making it easy to browse full-length articles as well as my notes. The desktop client can open tabs containing multiple PDFs and allows highlighting and Post-It style notes right on the article (although for now, these annotations are not kept in the cloud, so I can't highlight a paper at lab and retrieve the same highlighting when I sync Mendeley Desktop at home). I can sort my citations by title, author, publication date, date added to Mendeley, or by my custom tags. Mendeley is also smart enough to show me articles related to a tag even if I didn't tag them that way -- an article that I tagged "review" will come up when I select the "motor neurons" tag, if it talks a lot about motor neurons, even if I didn't add that tag myself.

Mendeley is compatible with EndNote (select any number of citations in Mendeley, export them as an EndNote XML file, and Cite While You Write to your heart's content) and with several word processing programs (obviating the need for EndNote), although it doesn't yet work with Microsoft Word on Macs. I've had no issue using EndNote as a middleman, however. Mendeley can also import citation information from EndNote, Zotero, CiteULike, and RefWorks, making it easy to transition from another reference management system (have not yet tried this myself, since I haven't been working on this project long enough to generate a huge reference database in another system). It's also free! If you're intrigued but not completely sold, check out some other reviews, or just download it and see for yourself.

Priorities

2009-12-14T23:12:00.001-05:00

The order in which I get things done (roughly) when sorting through a massive to-do list.

1. Quals. I had a written qualifying exam recently (we had to write a paper critiquing a journal article) and basically dropped everything else to work on it. I mean, if I mess this up, they kick me out of grad school, so I'd better take it seriously. (I've since heard back from the DGS that I passed. Woohoo!)

2. Teaching responsibilities. In general, I'm more likely to do work when someone else is depending on me than when only my own butt is on the line. This is especially true when the dependents are a bunch of undergrads, with whom I feel a special kinship because I used to be them. It's been wonderful working with the students this semester, and I'd hate to let them down in any way, so I'm very diligent about grading, preparing review sessions, and answering questions over email or the course message board. I'm also quick to volunteer for teaching-related tasks when my supervising professor asks around the pool of TAs. I find it rewarding. While there are many things that I don't know, I thankfully have a firm grasp of undergraduate level neuroscience, and I enjoy putting that knowledge to use. Especially when failed experiments have left me feeling like a useless moron.

3. Coursework. A lot of my coursework this semester has been seminar-based. This means listening to my classmates give a talk and providing them with feedback. I like hearing what they're up to, although I'm occasionally intimidated by all the super-smart folks in my program. I do everything I can to help them out, because they're my friends, and they've done the same for me. Classes also provide me with a lot of distinct, attainable goals (study for this test and ace it, research and write this paper, make this presentation and give the talk), unlike labwork, where the carrot seems to be constantly dangling just out of reach. When I finish my work for a class, it's really finished, and I can move on to other things.

4. Experiments. I'm still struggling to find the best strategy for Getting Things Done in the lab, especially as I juggle items 1-3 on the list above. Next fall, I'll be finished with quals, teaching, and courses, so it will be easier to plan my lab time. As it is, I'm trying to stay organized and break things into manageable chunks that can fit in around other obligations. My adviser has helped with this by encouraging me to think of smaller tasks (like, "order primers" rather than "complete Aim 1 of my NRSA") and to plan things out far in advance so I don't get overwhelmed. I've started adding these smaller action items to my calendar, and I feel very industrious when I have a full agenda (even if it contains things like "make LB/agar plates"). My labmates have also been extremely helpful, suggesting new things for me to try and training me in techniques. I have a long list of experiments planned for January. If all goes according to plan (hey, a girl can dream...), I should have lots of fresh data to play with in the next month or two.

5. Extracurricular activities. This is how I'd describe my work with Emory Women in Neuroscience (EWIN), Graduate Advocates for Work-Life Balance (GAWB), the Third Culture Journal Club, and other side projects (like organizing an event for Rebecca Skloot at Emory -- everything is coming together, so keep your eyes peeled for more information about that!). I find these projects inspirational when they're in the planning stage, and immensely satisfying when things work out. Even if the end product is nothing more than a successful meeting, I feel like I've done a good thing. I've concluded that I really like working with people on projects like these, and I'd like to keep it up when I move on to my future career. As it is, I don't have a ton of time to devote to these things, but I'm slowly building a network of people who have given me lots of help in bringing my (our) ideas to fruition.

6. Social life. Most of my local friends are fellow grad students, so even when we're swamped with work, we find some time to catch up over lunch on campus. My program is full of really fun people who can sometimes coax me out of my office and into a fabulous party. And, my live-in partner provides me with constant companionship and emotional support when I'm freaking out about a deadline. I struggle to make time for all of these important people (as well as the ones who aren't local -- my family, my friends from college and beyond...) and I hope I do a decent job. My partner and I eat a home-cooked meal together almost every night, and my friends and I keep in touch through Facebook when we don't have time to meet up for shenanigans.

7. Housework. Man... you don't even want to know how much laundry I have piled up right now.

8. Blogging. Sorry, guys.

Looking forward to checking more things off my list in 2010! I hope you all have a lovely holiday season and a restful break between semesters.

PhD Diary, Year Two: November, 2009

2009-11-12T14:47:00.001-05:00

The fall semester is starting to wind down. I'm currently working on an experiment that has been carefully timed to end the day before Thanksgiving, so I can visit family in Florida for the holiday. Hopefully, nothing will go awry. It will be nice to see my relatives again -- I haven't seen them since last Christmas!

The past month has been busy (aren't they all?), but satisfying. I had one week that seemed really overwhelming when I was looking at my calendar: grading the second exam for my TA assignment, meeting with a famous scientist who'd been invited to give a talk at Emory, trying to organize things for my own invited speaker(s), and presenting a short version of my proposed dissertation work (which I will be writing up for a pre-doctoral NRSA next semester) in my advanced graduate seminar. I was freaking out about these things, but somehow I managed to stay organized and get everything done. I even managed to have a little fun (if grading exams during commercial breaks of a football game can be considered 'fun'). I also scheduled a fabulous dinner date at Cakes & Ale for the end of the week, so I had something to look forward to. Although the grad student workload can be a little insane, I actually get a perverse thrill out of getting all of these things done. It's a boost to my self-confidence when I'm able to complete a seemingly daunting task. I may have to be careful about what I get myself into, though -- I keep hearing about cool extracurricular opportunities (undergraduate mentoring, graduate school organizations) and signing up for things. Eventually I will surely come to a point at which I cannot take on more work and expect to retain my sanity.

And speaking of taking on extra work, I'm also trying to organize an event for Rebecca Skloot on campus. Ms. Skloot is promoting her critically-acclaimed new book, The Immortal Life of Henrietta Lacks, which I think has broad appeal not only for biomedical scientists, but for many other members of the Emory community. If you're a fellow Emory person and you're interested in helping me scare up some funding, please contact me.

Presenting an abbreviated thesis proposal in seminar really helped me organize my plans for the research I hope to accomplish over the next few years. My adviser and my labmates provided a lot of input, of course. But, most importantly, the assignment forced me to start thinking through my arguments for performing each experiment, what the possible results might be, and what each result would mean in terms of my central hypothesis. It was also the first presentation I've given in grad school using the word "I" (instead of "we" or "they") when referring to the creator(s) of some cool science.

Next semester promises to be even crazier than this one -- I'll be taking four or five classes, including an intensive grant-writing course. I'm not sure when I'm supposed to get anything done in the lab. But, after this year, I will have fulfilled all of my coursework requirements, and I'll be free to set my own schedule (within reason... sometimes, my tissue culture cells end up setting my schedule, and they don't respect weekends). Definitely something to look forward to. In the meantime, I'll have lots to keep my occupied.

Visualize your CV

2009-11-03T16:03:00.001-05:00

My friend Liz shared this neat trick from ClueWagon: Paste your resume or CV into a word cloud generator like Wordle and see what comes out. Here's mine (click for larger version):

SfN 2009: Recap

2009-10-23T17:13:00.001-04:00

As many neuro-bloggers have noted, it is very difficult to keep up a good blogging regime during SfN. With lectures, symposia, and poster sessions all day followed by social activities all night (we closed down a bar on more than one occasion), the conference is pretty relentless. I returned to Atlanta Wednesday night, and I've been trying to synthesize the rest of my conference experience. I also managed to keep up a running commentary about some SfN events on my Twitter account (when I could find wifi at the convention center), so check that out if you're interested in 140-character summaries.

Some highlights from the conference: The SfN tweet-up, where I met other dual science/internet nerds and dragged a bunch of my fellow Emory students along for the ride; a special lecture by Dr. Ben Barres during which he gave an extended sub-lecture about diversity in science (and referred to a previous talk, "Some Reflections on the Dearth of Women in Science," which I was lucky enough to attend last year); a special lecture by Dr. Eric Kandel, who literally wrote the book on neuroscience; several jam-packed symposia in Theme A; evening socials with free beer (I sort of crashed a party intended for University of Iowa students, who welcomed me with typical midwestern hospitality); discovering some extremely relevant posters in my field of research; networking with dozens of fellow scientists from around the world (we are totally Facebook/Twitter/etc. friends now!).

So what have I learned from my first major conference experience? The first major lesson came in conquering my tendency toward shyness. I found most of the people I met at the conference to be quite friendly, but it took me a while to get over my feelings of intimidation when approaching other scientists. This was especially true at the poster sessions, when I initially hesitated to ask questions or discuss someone else's work due to my lack of experience with the subject material. I got over this after a few days, and although a few people treated me in a dismissive manner, I had some really good conversations about other peoples' science. I also learned a lot by example, noticing which posters were easiest to understand and which speakers had the most professional attitudes when presenting.

The second lesson involved time management. With dozens of events happening each day, it's impossible to do everything. After a few days of struggling with the schedule, I decided that it was okay for me to hop from symposium to symposium, catching the short talks that were most interesting to me and then moving on to other things. I did always make a point to wait until each speaker finished his or her presentation before I left, though. I found it irritating when people would stand and walk out during the acknowledgments slide, before the speaker received their applause. I know we're all busy, but couldn't you wait another 30 seconds, in the name of politeness? I also tried to leave myself some flexible time for wandering around posters and vendors, taking a coffee break, or following a new acquaintance to a recommended event.

The third lesson: Pack a lunch. Convention center food is shamefully overpriced, unhealthy, and not particularly palatable.

It's good to be home. I'm giving lab meeting next week to share what I've learned from SfN (I was the only member of my lab to attend -- the rest of the students and postdocs are more geneticists and cell biologists than neuroscientists, and my PI was too busy with a study section to go to the conference). I found two really cool posters that dovetail nicely with our work, but I have a lot of background reading to do before I can put those results into the proper context.

Since returning to the lab, I've also noticed that SfN seems to have given my contact information to a bunch of vendors. Last month I didn't even have a department mailbox, and the first piece of mail I received at the lab contained my credentials for the meeting. This week I noticed a pile of catalogs, flyers, and other promotional materials. That was a little disheartening. I may keep some of the catalogs for my coffee table, though -- I'm sure non-scientist houseguests would be amused by the listings for various rodent mazes, which featured some very cute mice.

SfN 2009: Day 2

2009-10-18T19:11:00.001-04:00

The second day of SfN left me in a great mood. I opted to take the Metra to and from the conference center instead of relying on the shuttle, as I was pretty traumatized by last night's never-ending return trip. The Metra station at Millennium Park is about a mile from my hotel, so I started my day by walking through downtown Chicago in the stillness of an early Sunday morning. It was cold and clear. I was amazed at how beautiful the city is; just walking and taking in the sights has been a great experience. Stopped at a Dunkin Donuts on my way to get some food and caffeine, then continued to the train station.

The Metra ride went smoothly and I made it to McCormick Place in time for my first event, the Time Management Workshop on combining family and science. This was of interest to me because of my work with Graduate Advocates for Work-Life Balance. The panelists were all faculty at different stages of their careers, with different family configurations. I enjoyed hearing about how they achieved their own balance, and was pleasantly surprised to hear a lot of focus on the pros of being a working scientist and a parent -- their kids get to travel the world, and labs can become a kind of extended family, if you surround yourself with supportive colleagues. Brief talks by the panelists were followed by a Q&A during which the workshop organizer solicited suggestions for how the Society for Neuroscience can help its members achieve the balance they need. The suggestions echoed my own opinions -- that SfN should help trainees lobby for better family-friendly policies at their home institutions (maybe they can get Emory to comply with the NIH's policy on paid parental leave for training grant recipients...), and that similar panels with speakers at the graduate student and postdoc level would be helpful for the junior members of the society who are considering their choices for the immediate future. I also learned that other neuroscientists are lobbying for the creation of new family fellowships, to support individuals with family obligations that might make their scientific careers especially challenging. Email addresses were exchanged. It was overall quite a positive event, although I got the sense that some members of the audience were really struggling. Workshops are good, but we also need to be proactive about policy reform. We have to help people like the woman who stood up and said she was considering leaving science over her institution's failure to accommodate her family needs, or the woman who is afraid of losing job offers due to pregnancy.

With these thoughts running through my head, I had time for a quick lunch (I think the food court salad bar is one of the better options -- the $12 price tag is kind of ridiculous, but you can really load up your plate and share with a friend. Plus, it comes with soup!) before Dr. Thomas Sudhof's special lecture, "From Synapses to Autism -- Neurexins, Neuroligins, and More." I'd heard about the genetic studies implicating these key players in autism spectrum disorders, but I hadn't heard all of the details. Dr. Sudhof's lab has created mice with a mutant form of neuroligin 3 that recapitulates the version of the gene seen in some autistic children. The mice have social interaction deficits, but they are superior to wild-type mice in certain learning and memory tests. Further study shows that mutations in neuroligin 3 seem to shift the balance between excitation and inhibition in the mouse brain -- inhibition is heightened in the cortex, whereas excitation is heightened in the hippocampus. Dr. Sudhof proposes that the proteins that maintain the structure of the synapse (proteins in the presynaptic cell involved in neurotransmitter release, as well as postsynaptic factors that are important for receptor scaffolding) form a biochemical family that is a major player in the etiology of autism.

After Dr. Sudhof's talk, I hung around to watch the Peter and Patricia Gruber Lecture. Each year, the Gruber Foundation presents a neuroscience award to a distinguished researcher (or team of researchers) to commend their contributions to the field. This year's award went to Dr. Jeff Hall, Dr. Michael Rosbash, and Dr. Michael Young for their groundbreaking work on the molecular underpinnings of circadian rhythms. Dr. Hall and Dr. Rosbash were both faculty at Brandeis while I was there earning my BS/MS (Dr. Hall has since moved on to the University of Maine), and it was a treat to see people that I used to pass in the dim-lit hallways of the old Brandeis science building up on that stage. The three honorees presented a series of short lectures describing the history of their work on Drosophila neurogenetics and the winding path that led to the characterization of per, tim, and other genes that contribute to the daily cycle shared by all of your cells.

By then I decided to hop on the 4:15 Metra back downtown. I grabbed a sandwich and a cup of soup at a cozy little cafe, read the New Yorker, and enjoyed some quiet time away from the 30,000 neuroscientists at the convention. Strolling around Chicago by myself reminded me of living in Boston, when I would often go for long walks in the city to explore, window-shop, and people-watch. Atlanta doesn't lend itself quite as well to those little adventures, and I miss them. I'm glad I had this opportunity to visit a new city and get a little vacation with my science.

Tonight I'm headed to the SfN social media tweetup at LaSalle Power Company. It's at 7:00 PM. I'm looking forward to meeting some other internet nerds among the thousands of science nerds. A few of us have been busily tweeting away throughout the conference (albeit hampered by a Twitter outage this morning!). In the meantime, I'll be reviewing the conference itinerary for tomorrow. Feel free to suggest any talks or posters that you think I ought to visit.

SfN 2009: Day 1

2009-10-18T01:05:00.001-04:00

Up too late hanging out in the hotel restaurant with new friends made on tonight's hellish shuttle ride (the bus driver got lost... it took me about an hour to cover the three miles between the convention center and my hotel). But, I had to blog about this:

A fellow Emory Neuroscience graduate student, Kim Maguschak, was recognized this year with SfN's Next Generation Award for her outreach work. Kim helps to organize the Atlanta chapter of the Society for Neuroscience, including most of the work for our large Brain Awareness Week campaign. Her efforts have helped send practicing scientists (including me!) into hundreds of Atlanta-area public school classrooms to teach kids about neuroscience. Congratulations, Kim!

SfN 2009!

2009-10-15T19:14:00.001-04:00

I'm headed to Chicago tomorrow morning to attend the annual Society for Neuroscience meeting. This will be my first time attending, and I hope to blog and tweet about the experience throughout. That may be dependent on the quality of available wifi, though. If you're reading this, going to the meeting, and want to meet up for a talk or a beer, let me know! I don't have a poster this year, so I'll be free to just take it all in.

Quote of the Day

2009-10-10T12:59:00.001-04:00

"Our research shows that women who had children during graduate school or within five years afterward and continued in their careers had as high a success rate as women without children. Not taking a break proved to be a successful strategy. And, as we shall see, the increasing number of family accommodations at universities, corporations, and other institutions allow more mothers to continue their careers without a lengthy interruption or detour into a second tier." -- Mary Ann Mason and Eve Mason Ekman, Mothers on the Fast Track: How a New Generation Can Balance Family and Careers

It's nice to have your mission validated, isn't it, my GAWB friends? (Thanks to Teresa for loaning me this book. Full review to come when I finish!)

'Tis the Season for Supporting Public Schools

2009-10-07T08:55:00.001-04:00

Those of you who get around the blogosphere may already be aware of the DonorsChoose Social Media Challenge. For those who haven't heard of it, I felt the need to write a post, because this fundraising effort is so awesome.

DonorsChoose is a charitable organization that works with public school teachers to fund educational projects. Teachers essentially write little grants, and DonorsChoose provides a platform through which those grants can be funded through individual donations from many different people. Projects raise money for field trips, microscopes, books, art supplies, games, and -- in some heartbreaking cases -- even paper, pencils, and food, for needy kids who can't get these things any other way. The folks at DonorsChoose also connect donors with the teachers they support, so that the teachers and students can provide thank-you notes. I have received these notes in the past. They are usually filled with adorable crayon drawings. Aww!

To drum up support for their estimable cause, DonorsChoose created the Social Media Challenge. During the month of October, bloggers and tweeters recruit their readers to donate through Giving Pages. When donations are made through these pages, they are tallied up for the blogger running the Giving Page, allowing social media users to compete in a "philanthropic throwdown."

Many science bloggers are participating in the challenge through the Seed Media ScienceBlogs Giving Page. Their combined efforts have raised over $9000 in the first week of October. You can check out the list of bloggers and see if there are any scientists who deserve your support in the challenge. Some are even offering offering tangible (e.g., t-shirts) and intangible (e.g., suggest a topic for a blog post) rewards to donors who support them.

And then there's Sarah Bunting. Through her blog, Tomato Nation, Sarah is attempting to raise $210,000 for DonorsChoose... this month. She and her readers have raised over $37,000, as of this post. In one week! To motivate donors, Sarah gathers fabulous prizes donated by fans of her work and gives them away to DonorsChoose supporters at the end of October. She also offers "mini-prizes" each day for funding a particular project. And if readers meet her fundraising goals, she does something silly to reward them (this year she promises to wear a tomato costume to Atlantic City casinos and videotape the ensuing hijinks).

But it isn't about the prizes. It's about coming together to do something great for kids. I've donated in support of several bloggers this month, but I'm really trying to support the school children who need our help. With that in mind, I donated a $50 Amazon.com gift certificate (thanks, credit card points!) to the Tomato Nation challenge as a prize for supporting this project. The teacher who submitted the project needs to raise a couple hundred dollars today (all projects on DonorsChoose have a deadline for funding; this one's is tomorrow) in order to purchase games for his high school dropout prevention program in Alabama. If you'd like to help, you can make a donation of any size through the link above. For a shot at the Amazon gift certificate, you must then forward your email receipt to Sarah (sars at tomatonation dot com), who will do a prize drawing later.

It's inspiring to see the donations piling up as October goes on. I know many readers of this blog are fellow poor graduate students, but if you can go without coffee and a bagel today and donate even $5 to one of these projects, you can make a difference. I hope you will.

Careers in Teaching

2009-09-28T23:21:00.001-04:00

Today I went to a career seminar sponsored by the GDBBS on Careers in Teaching. The Division does a lot of these seminars, and I try to take advantage of them to help combat my natural tendency toward "career planning," which at this stage consists mainly of sticking my fingers in my ears and chanting, "I'm not listening, la la la!" Okay, maybe not that bad, but it is hard to think about where I'll be after getting my PhD, since I've only just started my dissertation research.

Anyway, the seminar featured several terrific speakers. I guess it's not surprising that people who've made a career out of their passion for educating others are engaging and energetic ambassadors for their jobs. It was a pleasure to hear them share their experiences and their enthusiasm.

The first speaker, Dr. Leah Anderson Roesch, is the director of Emory's SIRE program, which is focused on helping Emory undergraduates participate in research. This is something that I feel strongly about, since my own undergraduate research experience made a huge impact on my own decision to become a scientist. I'm really excited whenever the undergrads in my TA course come to me with questions about research opportunities and graduate school. This may partly come from the fact that their interest validates my own life choices, but I think there's more to it than that. Undergraduate research builds confidence, independence, and curiosity. Students who see what it's like to actually work in their chosen field (not just science -- SIRE encompasses every department at Emory, from social sciences to arts and humanities to public health) are more engaged with what they're learning in classes. I truly believe that participation in programs like SIRE can be crucial to a student's educational and personal development. So, basically, I'm a big SIRE cheerleader. (I also hope to apply for one of their Graduate Fellow positions later in my graduate career. So awesome!)

But, I had already known about SIRE before I came to today's seminar. The Fellowships in Research and Science Teaching (FIRST) program, however, was new to me. FIRST is Emory's version of the NIH/NIGMS's Institutional Research and Academic Career Development Awards (IRACDA) program. Two FIRST fellows, Dr. Brandi Brandon Knight and Dr. LaTonia Taliaferro-Smith, spoke about their experiences with the program. FIRST offers three-year postdoctoral fellowships (so, my own participation would have to wait until the distant postdoctoral future...) that combine traditional research with intensive pedagogical training, mentored teaching, and independent teaching at minority-serving institutions. FIRST's mission is focused on course development using current educational techniques (especially those incorporating new technologies) in an attempt to better engage undergraduates in their classes. The fact that these exceptional teachers go on to work with traditionally under-represented populations of students is especially inspiring. And, of course, FIRST graduates (and graduates from the other 12 IRACDA postdoctoral programs around the country) are well-prepared for teaching-intensive faculty positions at small liberal arts colleges. Plus they still participate in traditional postdoctoral research -- and publish papers -- under the supervision of a PI at their primary institution. Frankly, the whole thing sounds pretty cool, although I'm sure the workload is sizable.

It was great to walk out of an hour-long seminar feeling excited about all the possibilities that lie before me. I may change my mind about undergraduate education later (perhaps after I have to grade my first exams this week...), but in general I think it's great to have these moments of reflection. I'm getting a PhD in neuroscience because I think neuroscience is fascinating, but I also have this dream about making a difference, which sounds great but can be hard to actually spell out in a five-year plan. One way to make a difference is to discover some amazing new scientific truth, of course, and it thrills me each time I uncover a new result that no one has ever seen before. But we can also make a difference through our interactions with other people. Someday my dissertation will be moldering in the stacks of the university library, quaintly out-of-date in the wake of the ever-expanding scientific frontier. But, as the bumper-sticker says (echoed by the many teachers in my family), "to teach is to touch lives forever." A warm and fuzzy sentiment to save up for those lonely nights in the lab.

Third Culture Journal Club

2009-09-25T10:13:00.001-04:00

Yesterday was the inaugural meeting of the Third Culture Journal Club, an organization for graduate students interested in interdisciplinary research. I felt like a bit of an impostor as I sat with a bunch of truly interdisciplinary students from Emory's Graduate Institute of Liberal Arts, but they assured me that they want to reach out to science students as well.

I enjoyed hearing what others had to say on this topic, and participating in the discussion. It was quite different from the sorts of journal clubs that I attend in the sciences -- we barely referred to the reading! Most science journal clubs engage in a figure-by-figure breakdown of the article, a lengthy critique of the methods, and an interpretation of the results in a broader context. Third Culture's discussion used the assigned articles mainly as a jumping-off point. Still, I found the reading helpful to put me in the right frame of mind. I'm not used to working with these nebulous terms, so the attempts at defining academic disciplines and inter/multidisciplinarity research were helpful to me. It was also refreshing to read a couple of non-science articles for 'school' -- imagine, spending less than an hour going over a five page document!

The group talked a bit about interdisciplinary initiatives at Emory. One student at the meeting helped form the Scholars Program in Interdisciplinary Neuroscience Research (so new it doesn't seem to have a website yet!). She talked about how different ideas of interdisciplinarity came up during the planning stages of the program, and how people had vastly different opinions on the matter: some feel the neurosciences are already interdisciplinary enough, while others feel that we should collaborate more with the social sciences and humanities. We decided that "interdisciplinarity" cannot be all things to all people, and that perhaps we should attempt to more specifically define our goals for a particular research initiative. We concluded that while certain questions are best addressed through interdisciplinary collaboration, one should not fall into the trap of slapping an "interdisciplinary" label on a project merely to generate buzz or funding, as not all work can be conducted this way. We also came up with the term "problem-based research" as an alternative to "interdisciplinary research." The distinction between the two will be a focus of next month's meeting.

One article from the assigned reading (Golde et al., 1999) used the Emory Graduate Division of Biological and Biomedical Sciences as an example of a successful interdisciplinary initiative. By putting all the life sciences under one "umbrella," Emory has freed graduate students from individual departments and thus allowed for more interdisciplinary research, or so the argument goes. In the ten years since the publication of this article, many other programs have followed in Emory's footsteps. In fact, all four of the graduate programs for which I interviewed had life science "umbrella" programs (in addition to the GDBBS at Emory, I visited the BBSP at UNC Chapel Hill, the IDP at UF, and the integrated PhD program at Albert Einstein College of Medicine).

As an insider in one such program, I'm not certain that they've achieved true interdisciplinary enlightenment. Each sub-program (there are eight of them in GDBBS) maintains its independence, setting its own standards for coursework, qualifying exams, and dissertation committees. Each has a Director of Graduate Studies, a Program Director, and other governing bodies. Outside of a first-year biochemistry course, students in different programs rarely interact. While we don't work for a specific "department," in many ways we might as well be separated along those lines, as the individual program boundaries have a similar effect. This was also true of most of the other "umbrella" programs I visited -- some of them had wildly different requirements for the different sub-programs, with variations in stipends, teaching responsibilities, and scholarship opportunities, among other things. Einstein was a notable objection, as their PhD program does not break itself down into smaller programs at all (though students become affiliated with a department once they join a lab).

There are some true benefits to the GDBBS, however. I do appreciate the fact that I work with students from the BCDB and GMB programs in my lab, even though it took me about a year to even learn what all the different program acronyms stand for (some of which seem a little redundant -- "Microbiology and Molecular Genetics" vs. "Genetics and Molecular Biology"?). My lab is in the Department of Human Genetics, and it wouldn't have occurred to me to apply to a genetics PhD program back when I was researching schools. Because I essentially have two 'departments' (Human Genetics and the Neuroscience Program), I'm exposed to a larger scientific network than I may have been with only one affiliation. The nature of GDBBS/Neuroscience at Emory meant that I could rotate in labs associated with many different departments (I also dabbled in Pharmacology and Neurology) before making up my mind about what I wanted to do. Still, if Emory had a Department of Neuroscience instead of a Neuroscience Program, I'm not sure that my rotation experience would have been noticeably different. So, while programs like GDBBS are a good start, there is more room for improvement.

In general, I support any effort to encourage graduate students to branch out from their tiny subfields into the broader academic world. I specifically chose a liberal arts university for my undergraduate training because I appreciated the opportunity to study things like Latin lyric and elegiac poetry alongside my neuroscience classes. While my own research isn't especially conducive to interdisciplinary exploration (not a lot of textual analysis can be done on the subject of neural tube development...), I'm glad that groups like Third Culture exist to help broaden my perspective. These conversations are worth having even if they don't fit into my dissertation.

PhD Diary, Year Two: September, 2009

2009-09-16T21:38:00.001-04:00

I've been struggling to come up with blog-worthy material lately. My rotation diaries were fun and easy to write, but now that I'm not rotating anymore, I need some new impetus to keep writing. I figured more diary-style entries would be easier to generate than other content, and will hopefully help me stay in the habit of blogging. I really enjoy reading other blogs, and I love getting comments from you all, so I really ought to put in the effort to keep this going.

With the semester in full swing, I've found myself struggling to manage my time. I'm not even taking any 'real' classes (I'm required to attend a weekly department seminar and a weekly journal club style discussion with my classmates), yet each week seems packed to the brim.

My first TA assignment has proved both time-consuming and rewarding. I attend regular lectures on Tuesdays and Thursdays, where I help keep track of attendance (a non-trivial task in a class of 99 students). The four other TAs and I have a weekly meeting with the course instructor to make sure we're all on the same page. I also hold a weekly review session, which thus far has been attended by about a dozen students each week. Finally, I had the opportunity to give one lecture from the syllabus during regular class time, which was my first real experience with that kind of thing. I talked for an hour about nervous system development, axon guidance, and synapse formation. Unfortunately, the class is an hour and fifteen minutes long... but students rarely complain about finishing early. I wanted to leave ample time for mishaps and questions, but I should have had some back-up "optional" material to throw in if I didn't use all the allotted time. Live and learn! Other than that, I think things went well. I've had enough practice giving talks at lab meetings and in classes that I'm over my stage fright and fairly competent at public speaking; I just wanted to do a really good job for these students. I've found the undergraduates in this course to be excellent students overall, always prepared for review sessions with thoughtful questions, so I don't think they'll suffer much from having a newbie lecturer for a day.

I'm also working in the lab, of course. After I spent most of the summer struggling with a project, my adviser and I consulted with an expert in the department. He considered my findings and the relevant published data relating to the project and concluded that I was chasing a nonexistent gene product. D'oh. It does make me feel better about all those failed experiments, at least. Since then I've had some time to regroup and I'm working on a couple of things in parallel.

One project involves growing cells in culture for many days, and the cells need attention even on the weekends. I don't mind Saturday morning jaunts to the lab, but because the bus I take to campus doesn't run on weekends, and my partner and I share a single car, I have run into some logistical issues. This weekend my partner will take the car to visit his parents in Florida, and thus I am unable to start a new experiment until next week. A labmate did volunteer to help me out, but I told her not to bother with my experiment unless she has other reasons to come in on Saturday and/or Sunday. In the meantime, I have other stuff I can work on.

Finally, I've become fairly involved with some student groups on campus, and the fall semester has brought lots of meetings and other events. The Third Culture interdisciplinary journal club has its first meeting next week (complete with complimentary coffee and bagels!). We'll be discussing interdisciplinarity in research and reviewing some articles on the subject. Subsequent meetings will focus on more specific topics that have interdisciplinary appeal. I've been thinking about history of science and similar subjects, but could use some ideas if you've got 'em.

I'm also really excited about the work I'm doing with Graduate Advocates for Work-Life Balance. The senior students who founded the group have already done a lot to explore issues of work-life balance for graduate students at Emory, but they've allowed me to share my opinions with them. Our eventual goal is to implement more progressive policies for parental leave, child care, elder care, and similar issues that affect the graduate student body. Some administrators have expressed interest in our projects, and we'll be speaking at the next meeting of the Graduate Student Council, so we're pretty psyched. We have a long way to go, but we're making some promising first steps, and meeting with the other students in the group is a continuing source of inspiration for me.

So, that's what I'm up to. I really want to get a new Research Blogging post out in the near future -- I'm presenting a critique of a Journal of Neuroscience paper for my journal club / seminar, so I have some material ready. It's just a matter of finding the time to type it up... always a challenge.

Qualification

2009-09-02T10:07:00.001-04:00

I have updated my Blogger profile to say "second-year neuroscience PhD student," for two reasons. First, the semester has officially begun and the new first-year students are on campus. Second, and perhaps more important, I passed my written qualifying exam! (I will also have an oral exam at the beginning of my third year, which I must pass to achieve candidacy.)

Audio Entertainment

2009-08-10T14:12:00.001-04:00

Sorry for the lack of blogging. (I'm starting to sound like The Least Interesting Man in the World!) I've been ramping up for my qualifying exam, which occurs this Thursday. After that I've got an intensive TA prep course and our program retreat to deal with, not to mention classes, teaching, working in the lab, and participating in a few student organization... but I do hope to step up the blogging as well.

In the meantime, I thought I'd share a few of my favorite science podcasts. Scientists spend many not-so-glamorous hours on boring, repetitive tasks. Whether you're photographing things with a microscope, quantifying cells, sectioning tissue, or just pipetting the same solutions into a hundred little tubes, it helps to have an mp3 player handy. When I tire of listening to "The Rise and Fall of Ziggy Stardust and The Spiders From Mars" (okay, I never tire of it...), I put on some science talk. Then listening to my iPod becomes work-related, and I'm less tempted to yell "Wham, bam, thank you ma'am!" in the middle of the lab.

Many of your favorite science journals have podcasts nowadays. Nature Podcast summarizes top stories from the journal each week and offers other specialized audio programming as well (including my favorite, NeuroPod). Not to be outdone by Nature, Science has a weekly podcast of its own. Cell rounds out the big three, although those slackers only produce a new podcast once a month.

Science podcasts targeted to the general public include NPR's Science Friday and NPR: On Science podcasts. The Naked Scientists also covers a broad range of topics, including science experiments you can do at home, and answers to listeners' science questions.

For more neuroscience-specific discussion, I really love All in the Mind by Australia's ABC Radio National. They bring a human angle to stories about mental health, psychology, and neurology, often interviewing patients and their families as well as scientific experts. Finally, I recently discovered the Brain Science Podcast, which recently featured an hour-long interview with my first scientific mentor, Dr. Eve Marder. I've only listened to a few podcasts so far, but the host, Dr. Ginger Campbell, is great at getting the scientists she meets to talk about their lives and careers as well as the details of their research. For example, I really enjoyed hearing Eve discuss what it was like to be a female graduate student during the Vietnam War era (when the number of American women in science jumped suddenly, as men stopped being able to defer the draft for graduate school).

Once you download some of these great science podcasts, you probably won't even miss my lackluster blogging! I hope you enjoy them as much as I do, and I'll see you on the other side of this crazy August.

Emory Blog Update

2009-07-15T08:58:00.001-04:00

It looks like Emory has called off its dogs with respect to Dr. Doug Bremner and his blog. I'm relieved to hear that the whole thing was a "misunderstanding."

Hat-tip to Abel Pharmboy for bringing this to my attention.

Supporting Women in Science

2009-07-14T11:37:00.001-04:00

During my blog hiatus, I was nominated for my program's Institutional Predoctoral Training Grant. Six students from the neuroscience program are nominated each year (as long as NIGMS keeps renewing our grant!). The funds provided by this grant will support me for the next academic year, providing my stipend (taking the financial burden off Emory) and fees (taking the financial burden off me) as well as funds for travel, research equipment, and hosting a guest speaker.

I'm thrilled to have been nominated for this grant, and I look forward to all of the exciting opportunities it has created for me. With these travel funds and my NextBio travel grant, along with support from my mentor, I will be attending the annual Society for Neuroscience meeting in the fall. Some classmates and I are registering for the conference and booking our hotel rooms today. We're psyched!

I've also been searching for a guest speaker to invite to our program seminar. My mentor made some suggestions based on people whose research would interest the department and who are known for giving engaging talks. I looked up the people on her list and did some searching on my own to narrow things down to a few candidates. And, during the course of my search, I decided that I want to invite a female speaker.

My graduate program, like most in the life sciences, has a predominantly female student body. It also has noticeably fewer female faculty (again, like most life science programs). While our seminar series has done a good job of bringing diverse guest speakers to Emory in the past, I felt that this was a rare opportunity for me to have direct influence on the gender balance of faculty who will interact with our students. Numerous research studies have shown that even people who strive for fairness when selecting candidates from a mixed gender pool will often bias themselves toward men. (See Prof. Virginia Valian's excellent slideshow tutorial on gender schemas, especially the bit in Tutorial #1 on gender bias in peer review, which begins at slide 15.) This is true whether men or women are evaluating the candidates.

To avoid this pitfall, I made a conscious effort to create a pool consisting entirely of female candidates. I joked about my "blatant sexism" with my adviser, but it's something that I take seriously. It did feel a bit strange and arbitrary to me as I removed speakers from my list simply because they are male, but I don't think a single missed opportunity to speak at our seminar series will have a large impact on their professional success. (All of the male speakers I was considering have already achieved professional success in the form of full professorship, selection by HHMI or NAS, etc.) I'm also sure that some other students on the training grant will end up inviting male speakers. But choosing to bring a female professor into my program for a talk could have a significant benefit, especially if students and postdocs who attend the talk are seeking a mentor for the next stage of their scientific training. Female role models in the sciences can be few and far between, so I think it's worth something to expose my classmates to more of them.

This is, ultimately, a small thing. But many small efforts can add up to larger achievements. When I was elected to a position within my program's executive committee, a classmate emailed to congratulate me. She also wrote, "I hope you plan on using your feminist powers for good." When I made this decision, I was thinking of her, and of the other amazing female graduate students who make my program great. (Our male graduate students are also great, I should add, but they don't often engage me about my feminist powers.) I'm doing what I can.

I've Been Away

2009-07-12T15:55:00.001-04:00

It seems that this blog has been on the back burner for over a month. Sorry about that! It's been a busy time for me -- I finished my last rotation, visited friends and relatives out of state, moved to a new apartment, and joined the lab where I will conduct my dissertation research. Things are going well for me, but I haven't had much time for blogging.

Also during my blogging hiatus, this happened. I find it worrisome, to say the least, and I've been thinking a lot about my decision to write under my real name without hiding my university affiliation. Perhaps it would be wiser to avoid the hornet's nest of new media at my university for the time being. But that doesn't feel right to me. If someone from my institution has a problem with what I write, they are free to contact me to discuss it. If I'm ordered to obscure my school's name (which doesn't really accomplish anything, given that interested parties are free to Google me...) I will comply. Until then, I will continue writing about my experiences practicing the science that I love, and hope that my university comes to a more sensible position on honest, open lines of communication between researchers and the blog-reading public.

More Travel Grants Available!

2009-05-29T12:59:00.001-04:00

As some of you may know, I recently received a $500 travel grant from NextBio, makers of a free web-based "curated, correlated database of public data, integrated literature, clinical trials, and scientific news." The grant can be used to attend the scientific conference of my choice, which is awesome.

Well, they're at it again! If you're a graduate student or medical student interested in applying for a travel grant, check out the NextBio grants website. To apply, you must submit a one-page essay describing how you've used NextBio tools in your research. The deadline for applications is June 30, 2009, and recipients of the award will be notified by July 15. It looks like the company has decided to award grants like this on a continuing basis, which is great news for poor grad students everywhere.

TRP Channel Variations Determine What's "Too Cold"

2009-05-29T12:46:00.001-04:00

In the fairy tale of Goldilocks and the Three Bears, Goldilocks encounters three bowls of porridge in the bear household. Papa Bear's porridge is too hot; Mama Bear's porridge is too cold; Baby Bear's porridge is just right. Why would Papa Bear and Mama Bear choose to heat their porridge to non-optimal temperatures? A new study by Benjamin Myers et al. published in PLoS ONE suggests that their perception of "just right" depends on their TRP channels.

Okay, it's unlikely that three members of an anthropomorphic bear family would possess significantly different temperature-sensitive ion channels. But the paper shows that warm- and cold-blooded species living in different environments have evolved ion channels with different temperature thresholds to help them maintain a body temperature that is "just right."

Transient receptor potential (TRP) ion channels are responsible for many different sensory functions. The first TRP channel was discovered in the fruit fly, where it plays a role in visual signaling. Many other TRP channels have since been found. Though these channels share a similar structure, they contribute to many different sensory systems, including touch, pain, taste, and smell. A class of TRP channels also responds specifically to temperature, allowing nerve endings in the skin to sense heat and cold. Interestingly, the channels also detect certain chemicals that create a hot or cool sensation even without a change in temperature. In 1997, we learned that the heat-sensitive TRPV1 channel also responds to capsaicin, the molecule that makes chili peppers taste "hot" (Caterina et al.). In 2002, other research showed that TRPM8, a cold-sensing ion channel, can be activated by the minty freshness of menthol (McKemy et al.; Peier et al.). But although we have learned a lot about the function of temperature-sensitive channels in mammals, not much work has been done in other model organisms.

Myers et al. examined the TRPM8 channel in a commonly used cold-blooded model organism, the South African clawed frog (Xenopus laevis). They wanted to see whether this species, with a core body temperature and preferred environmental temperature much lower than that of mammals, would have a different range of temperature sensitivity in its TRPM8 channels. They hypothesized that these animals would have channels tuned to temperatures appropriate for their ecological niche, meaning that they would require a colder temperature to become active than the TRPM8 channels of a warm-blooded mammal or bird.

To test this theory, the researchers dissected out the dorsal root ganglia (DRG) of several frogs and used calcium imaging to measure the cells' responses to different temperatures. The DRG is the portion of the spinal cord that contains the cell bodies of sensory neurons, including the cells that produce temperature-sensitive nerve fibers. Thus, the cold-sensitive cells in the DRG express the TRPM8 channel. Calcium imaging involves use of a fluorescent dye that produces light when exposed to calcium inside a neuron. Because calcium influx is related to neuronal activity, we can use the fluorescent intensity to determine which neurons respond, and how strongly, to a given stimulus.

About 23.7% of the X. laevis DRG neurons responded to menthol, the chemical activator of TRPM8. Similar percentages of menthol-sensitive neurons are seen in mammalian sensory ganglia. Frog neurons differ from those of mammals, however, when the neurons are stimulated with cold temperatures instead of menthol. While rat neurons have a thermal activation threshold of 25.4°C, frog neurons have a much colder threshold of 9.6°C. Thus, a frog TRPM8-positive sensory neuron requires a much colder temperature to become active and produce a "cold" sensation.

Myers et al. wanted to be sure that this change in temperature threshold was caused by differences in the TRPM8 channel and not some other difference between rat and frog sensory neurons. Therefore, they expressed frog, chicken, and rat TRPM8 in oocytes (egg cells which do not normally express any ion channels; this is a common experiment used for studying ion channel physiology in an isolated system). Voltage-clamp recordings were used to measure the changes in oocyte membrane potential caused by activation and opening of the TRPM8 channels. The oocytes expressing X. laevis TRPM8, as well as TRPM8 from the related frog species X. tropicalis, displayed a much lower activation temperature than the oocytes expressing chicken or rat TRPM8. This experiment also showed a slightly higher activation temperature for chicken TRPM8 than rat TRPM8, which is consistent with the elevated body temperature of birds compared to mammals.

The differences in the temperature-sensitive properties of TRPM8 channels between species occur because of slight changes in the ion channel's structure through evolution. X. laevis TRPM8 differs from rat TRPM8 in about 25% of its amino acids. The differences in protein structure allow the ion channels to exhibit slightly different responses to temperature, even though they are similar enough to retain their general TRP structure and cold sensitivity.

The researchers summarize their findings as follows:

Within visual and chemosensory systems, stimulus detectors (receptors) undergo great functional diversification as organisms evolve to inhabit a wide range of ecological niches. Our findings demonstrate that genes encoding somatosensory receptors display the same capacity for adaptation to species' environmental conditions. Specifically, we have shown that a cold receptor can be tuned to respond within a temperature range most relevant to the normal resting temperature of the primary afferent nerve terminal, whether determined by an internally regulated core body temperature or the environmental milieu.

They go on to add that it is not clear whether the X. laevis and X. tropicalis TRPM8 channels are specifically tuned to the niches of these two species, or whether they represent a universal amphibian cold-sensitive channel that does not vary between frogs inhabiting different environments. As we sequence the complete genomes of more organisms, it will become possible to search for genes homologous to TRPM8 in other cold-blooded species and compare them to these frog channels. The authors add, "It may also be interesting to examine species that experience substantial variations (short- or long-term) in environmental temperature, as there may be corresponding changes in TRPM8 expression and/or function that allow for optimal temperature detection under such circumstances." Some cold-blooded species become dormant during the winter months, and it would be informative to see whether their temperature-sensitive neurons exhibit different properties during dormant and active seasons.

This research further elucidates how evolution has shaped individual species to thrive in different environments, down to the smallest molecular details. Frogs, rats, and chickens, like Goldilocks, sense heat and cold while searching for a temperature that is "just right." But what's good for one species might not suit another. Their specialized ion channels allow them to appropriately respond to thermal stimuli -- even the ones that don't like porridge.

References

Caterina M.J., Schumacher M.A., Tominaga M., Rosen T.A., Levine J.D., et al. (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389 (6653): 816–24

McKemy D.D., Neuhausser W.M., Julius D. (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416: 52–58.

Myers, B., Sigal, Y., & Julius, D. (2009) Evolution of Thermal Response Properties in a Cold-Activated TRP Channel PLoS ONE, 4 (5) DOI: 10.1371/journal.pone.0005741

Peier A.M., Moqrich A., Hergarden A.C., Reeve A.J., Andersson D.A., et al. (2002) A TRP channel that senses cold stimuli and menthol. Cell 108: 705–715.

Synaptic Vesicles Are Not All Created Equal

2009-05-27T16:42:00.001-04:00

A pair of articles in Nature Neuroscience this month provide new insights into the mechanisms underlying spontaneous and evoked release of synaptic vesicles. Spontaneous release of a single vesicle (a "mini" release event) at a synaptic site was first observed over 50 years ago. A mini is considered to represent a single "quantum" of neurotransmitter, therefore the quantal theory of neurotransmitter release states that all synaptic responses will reflect some multiple of the response to a mini (depending on the number of neurotransmitter vesicles released). This provides a convenient way to study neurotransmitter release, and many experiments have been conducted under the assumption that minis are a reliable shorthand for evoked synaptic responses. Scientists have debated the mechanism behind spontaneous release, however. Are minis produced by the same vesicles as those that produce evoked neurotransmission (that is, release of neurotransmitter in response to an action potential)? A paper by Naila Ben Fredj and Juan Burrone address this question, showing that two non-overlapping pools of synaptic vesicles exist in rat hippocampal neurons for spontaneous and evoked release. Are minis truly random, or are they responding to signals that we don't fully understand? Jun Xu et al. show that the same calcium-sensing molecule, synaptotagmin-1 (Syt1), is responsible for regulating spontaneous and evoked release of synaptic vesicles, and that Syt1 further regulates some yet-unknown sensor responsible for other mini release events. Both of these papers reveal new complexities behind spontaneous vesicle release that challenge some of our fundamental assumptions.

Synaptic vesicle release depends upon molecules called SNAREs, which are present on the vesicle (v-SNAREs) and the target membrane (t-SNAREs). Complementary SNAREs allow vesicles to fuse with the target membrane and release their contents (neurotransmitters) into the synaptic space. The prevailing theory of release states that these fusion events occur spontaneously at a very low rate, producing minis. An action potential causes an influx of calcium into the presynaptic cell, which activates a calcium sensor and greatly increases the probability of vesicle fusion, creating a large, synchronized release of neurotransmitter from many vesicles.

The first paper I will discuss, by Fredj and Burrone, addresses the assumption that spontaneously-released vesicles are the same as evoked vesicles. If minis are caused by the random fusion of synaptic vesicles with the cell membrane, then we would expect spontaneously-released vesicles to resemble all other vesicles, with the only difference being that they accidentally fused without receiving a calcium signal. Previous experiments have indicated that this is probably not the case (Sara et. al, 2005), but Ben Fredj and Burrone developed a new technique for labeling presynaptic vesicles that supports the notion of a separate pool of spontaneously-released vesicles. Vesicles that have released their contents are recycled by the cell, allowing them to be refilled with neurotransmitter and used again later.

The researchers created a tagged version of an internal vesicle protein called VAMP2, which they called biosyn. Fluorescently-labeled streptavidin will permanently bind to biosyn. If streptavidin is present in the synaptic space, it will label the biosyn that is exposed when vesicles fuse to the cell membrane. This allowed the researchers to visualize active, fused vesicles in a living synapse under different conditions. After verifying that biosyn is a reliable measure of spontaneous and evoked fusion events, and that the tagged protein does not interfere with normal synaptic processes, they went on to test whether spontaneous and evoked release events use the same populations of vesicles.

After testing biosyn labeling of spontaneous and evoked vesicle release, Fredj and Burron noticed that they saw only about half as much biosyn signal when examining spontaneous release, compared to evoked release. This occurred even though the vesicle populations appeared to be saturated (that is, the biosyn signal reached a maximum level after a sustained period of release, indicating that all of the available vesicles had already fused and been labeled with fluorescent streptavidin). This could mean that spontaneously-released vesicles represent a sub-population of vesicles that can undergo evoked release, or it could mean that the two types of release draw from distinct vesicle pools, with fewer spontaneous vesicle than evoked vesicles.

To distinguish between these two possible explanations, the scientists sequentially labeled evoked and spontaneous vesicles within the same cell using two different colors of fluorescent streptavidin. They describe that experiment as follows:

Synapses were first stimulated with a saturating stimulus of two 90-s depolarizations in the presence of strep488 [green streptavidin], which strongly labeled the entire recycling pool. A further depolarizing stimulus in strep594 [red streptatividin] resulted in no further labeling (or very small amounts of labeling), as all biosyn binding sites were occupied by strep488, confirming that our depolarizing stimulus mobilized all possible vesicles. On the other hand, after labeling the recycling pool with strep488, a further 15-min exposure to strep594 in conditions that would only allow spontaneous fusion events resulted in a substantial amount of labeling.

The data show that two different populations of vesicles are exposed to the fluorescent streptavidin probes under different release conditions. This prompted them to ask, "If the recycling pool of vesicles cannot account for spontaneous release, then where do these vesicles come from?" They propose that the spontaneous vesicles may come from the so-called "resting" pool. This is the name given to a previously-identified pool of vesicles that are not mobilized by neuronal activity. Further experiments by Fredj and Burrone provide evidence that this resting pool does provide the vesicles for spontaneous release.

A News and Views summary of the paper gives us more to think about:

The big question now becomes what other differences might exist between these vesicles besides the pools that they come from. Are they released from different locations in the presynaptic terminal, as suggested by a recent study? Does their protein and/or lipid composition differ? We can take some comfort in Fredj and Burrone's observation that the sizes of the evoked and spontaneous pools were highly correlated in individual axon terminals, consistent with previous studies. Further experiments will be required to identify all of the similarities and differences between these two forms of vesicle fusion and validate the continued use of spontaneous release to characterize evoked transmission.

Another paper from the same issue of the journal, by Jun Xu et al., indicates that while spontaneously-released vesicles may be drawn from a separate pool, they are using the same calcium sensor as evoked release (contrary to the belief that minis are, by definition, calcium-insensitive). They studied spontaneous (mini) and evoked inhibitory post-synaptic currents in cultured cortical neurons. While removing extracellular calcium from the culture medium depressed evoked currents more strongly than minis, the application of the membrane-permeable calcium chelator BAPTA blocked over 95% of minis. Meanwhile, applying caffeine (which increases intracellular calcium availability) increased the number of minis observed. This implies that while evoked vesicle release depends strongly on extracellular calcium influx, even minis are not calcium-independent -- some calcium must be present to trigger a spontaneous release event.

Evoked neurotransmitter release is known to be regulated by the calcium sensor synaptotagmin. Somewhat paradoxically, genetic deletion of synaptotagmin-1 (Syt1) causes an increase in the number of minis, leading to the theory that this protein both allows evoked release and prevents spontaneous release through some sort of clamping mechanism. But as the authors note, "The clamping hypothesis ... argues against the notion that spontaneous release may be biologically meaningful, as it is difficult to imagine how an accidental byproduct of evoked release could control a physiological process. Moreover, the clamping hypothesis fails to explain why at least some mini release is Ca2+ dependent."

Xu et al. decided to better elucidate the role of Syt1 in spontaneous vesicle release. By studying minis in neurons lacking Syt1, they found that the upregulated minis in those cells were still calcium-dependent (they, too, could be blocked by BAPTA). They showed that the synapses with no Syt1 seemed to exhibit greater calcium affinity than wild-type synapses. This indicates that Syt1 is not acting merely as a clamp to block spontaneous release in normal cells, but that some other, more sensitive calcium sensor is able to produce spontaneous -- but not evoked -- vesicle release in the absence of Syt1. This was true for both excitatory and inhibitory synapses.

One explanation for this result would be that Syt1 serves as the primary calcium sensor for spontaneous release, but that an unknown sensor, normally clamped by Syt1, can lead to spontaneous release in Syt1's absence. To test this, Xu et al. generated neurons expressing mutant varieties of Syt1 with different calcium affinities. If Syt1 is indeed responsible for both evoked and spontaneous release, one would predict that changing the calcium affinity of Syt1 would create a commensurate change in the magnitude of both spontaneous and evoked release. Indeed, this is what they found. The result held true when they tested the different Syt1 mutations in brain slices as well as in cultured neurons.

The authors leave us with this conclusion:

Evoked and spontaneous neurotransmitter release are generally considered to represent distinct types of release that are differentially regulated. Their distinct natures are evidenced by the fact that spontaneous release is maintained in the presence of the sodium-channel inhibitor TTX, which abolishes action potentials and evoked release. We found, however, that despite their differential regulation, these two types of release are mechanistically identical in that they both are triggered by Ca2+ binding to Syt1. The major evidence for this conclusion rests on the three Syt1 knockin mutations that we used. We previously demonstrated that these mutations either increase Ca2+-dependent binding of Syt1 to SNARE complexes or decrease the apparent Ca2+ affinity of Syt1 binding to phospholipids. In a direct comparison of all three knockin mutations, we found that they cause a corresponding change in evoked release and a precisely equivalent change in spontaneous release. ... Moreover, our results support previous suggestions that spontaneous release is physiologically important. Ca2+ regulation generally implies a physiologically controlled function; thus, the finding that spontaneous release is controlled by Ca2+ binding to Syt1 implies a physiological role... Many neurotransmitters and neuromodulators act by increasing or decreasing presynaptical Ca2+ concentrations, suggesting that these agents may control synaptic circuits, at least in part, by regulating Syt1-dependent spontaneous release without triggering action potentials.

Of course, this article also leaves us with some burning questions. What is this second calcium sensor that is clamped by Syt1? Why is it so sensitive? What important physiological roles are being played by these highly-regulated mini release events? Clearly, more research is needed into these areas.

In conclusion, we've learned from this month's Nature Neuroscience that spontaneous release events are not the same as evoked neurotransmitter release. Although these two types of synaptic vesicles use the same major calcium sensor (and are both calcium-dependent, contrary to popular belief!), there exist separate pools of spontaneous and evoked vesicles that respond differently to intracellular calcium fluctuations, and never the twain shall meet. It will be interesting to see where we go from here, teasing apart the distinct roles that these two types of vesicles play in neurotransmission.

References

Fredj, N., & Burrone, J. (2009). A resting pool of vesicles is responsible for spontaneous vesicle fusion at the synapse Nature Neuroscience, 12 (6), 751-758 DOI: 10.1038/nn.2317

Xu, J., Pang, Z., Shin, O., & Südhof, T. (2009). Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release Nature Neuroscience, 12 (6), 759-766 DOI: 10.1038/nn.2320

Sara, Y., Virmani, T., Deák, F., Liu, X., & Kavalali, E. (2005) An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission. Neuron, 45 (4), 563-573 DOI: 10.1016/j.neuron.2004.12.056

Scientiae: Moving Forward

2009-05-26T11:15:00.001-04:00

How are you moving forward in life? Are you close to your degree, tenure, sabbatical, or summer holiday? Is that paper almost ready to go out the door? Is your baby almost potty trained or are you training for a marathon? What keeps you moving forward in your science, work, and life? Is it the drive to cure a disease, make the world a more sustainable piece, or discover something that no one else knows? Is it the promise of exciting data at the end of a long assay? Is it the thought of people calling you Dr.? Is it your daughter's smile when she wakes up in the morning, or the enthusiastic tail wagging of your dog? When things get tough, how do you motivate yourself to move forward?

The "moving forward" theme is an appropriate one for this time of year. After a two-year break while working as a research assistant, I once again find myself in step with the academic calendar, when May marks the end of the year. It's a bit unsettling to think that school has been the major focus of my life for so many years. When I was working full time, I felt a bit of resentment when I didn't get a summer vacation -- but then, I didn't really take summer vacations in college (I spent each summer taking classes, doing research, or both), and I'm not getting too much of a break this year, either.

Even so, I've finished the first year of my PhD work. That is such an exciting accomplishment. I haven't taken my written qual yet, but based on my grades in my classes I'd say I'm doing well. For someone who spent many years as a squeaking-by slacker, and made some rather embarrassing grades in college, this is a big deal. I spent much of my academic career feeling smart, but not particularly successful. Now I'm actually feeling a little hint of pride in my accomplishments, which is a good feeling, although I worry about things going to my head. When I receive independent confirmation of my success, like an A in a course or some praise from a professor, my self-esteem actually seems grounded in reality.

Related to that self-esteem is the idea that I might actually be of use to other people. In the lab, I'm starting to come up with my own ideas for experiments. In other academic settings, I've been elected as a student representative on my program's executive committee, I'm working with a cool group of students from other departments on an interdisciplinary journal club, and I'm looking forward to TAing my first class in the fall. All of these things make me feel like I'm part of a team, doing important work that might even have some impact on the outside world. My ideas might contribute to a publication, a policy, an inspiration. And, in my personal life, I recently heard from my aunt that my teenaged cousin declared a science "major" (her high school has students on different themed academic tracks). I'm sure I can't claim to be the sole determining factor in that choice, but I like to think that I've been a good role model for her, and that I can be there to offer her advice as she continues her education.

Overall, I'm in a good place right now. I have new challenges to face in the next year, and I continue to fret over failed experiments, family crises, and the legions of bugs that have settled in my kitchen, but I draw strength from some great support systems. Quals and roaches had better watch their backs.

Written for scientiae-carnival.

Rotation #3 Diary: Week 8

2009-05-11T15:44:00.001-04:00

I'm now in the last week of my third rotation. Soon I will be choosing the lab where I'll spend the rest of my graduate school career. Thankfully, I'm in the happy position of choosing between several good labs. I haven't completely made up my mind, but I am leaning in one direction. I hope to sort everything out and join a lab by the beginning of June. If any former or current grad students would care to offer me some advice on making this decision, I'd be happy to get your input!

Last week I presented my rotation work at lab meeting. I made a little PowerPoint presentation that went over my progress on a couple of projects, complete with cute cartoon mice and screenshots from the gene sequencing software I've been using. Then, much to my horror, I deleted the entire thing 30 minutes before the meeting. I know I should have backed it up, and I had intended to. My original plan was to fine-tune the presentation the night before, which would have involved transferring it from my laptop to my desktop either by email or by flash drive. Unfortunately, I spent the night before the meeting at the emergency room, being treated for a bad allergic reaction to a bee sting. (It really wasn't my week...) So, I got no work done, and never transferred the file between computers, and thus had only one copy. Which I deleted. As Charlie Brown would say, "AAUGH!"

Fortunately, my PI and labmates were understanding of the mishap, although they did scold me for not making a backup copy. (I know. I know!) I gave lab meeting as a "chalk talk" instead, drawing diagrams on the board when I needed to, but mostly just talking and glancing at some hastily-scribbled notes to remind me of the details. Despite the awkwardness, this forced me to really explain the reasoning behind what I did and summarize the relevant results, rather than being like, "Look! I ran a gel! And here it is!" Hopefully the lab doesn't think I'm too much of an airhead, despite my technical difficulties.

More lab foibles: We transformed some bacteria last week. After spending a while cloning and sub-cloning, we finally had some DNA plasmids that we wanted to make in large quantities. This is done by tricking bacteria into taking up the DNA, i.e. transforming them, and then growing cultures of the bacteria so we can extract plasmid DNA from them once they've been fruitful and multiplied. I'd done transformations before using heat shock (putting the bacteria into a hot water bath for a minute or two), but this protocol called for electroporation (zapping the bacteria with electricity). No one in the lab had used the electroporation machine before, and our first run did not go too well. In fact, a very impressive spark was produced, along with a crackling sound and a strong aroma of barbecued competent cells. After daring everyone in the lab to smell the tube, we adjusted the settings on the machine and it seemed to be okay after that. No more fireworks occurred, and my transformed bacteria grew on some ampicillin plates, so it worked for at least some of them. (The plasmid we put into the bacteria contains an ampicillin resistance gene, so we know that successfully transformed bacteria will grow even when treated with that antibiotic. The untransformed bacteria die when you put them in ampicillin.) Now I've selected transformed bacterial colonies and grown enough of them to make DNA preps. We'll have to do some more analysis to see which colonies have the plasmids we want -- some of them might have recombined in weird ways, which isn't desirable. Progress marches on, with tiny little steps. Someday we'll make these into a lentivirus, honest.

I also had my last class of the semester last week. (We had our final session of my graduate seminar at a pub. It was quite grueling.) This August, I'll be taking my written qualifying exam. Until I pass that, I don't want to jinx myself by updating my Blogger profile from "first-year" to "second-year." But, I am very happy to be one year closer to a PhD. Next year I'll be working on dissertation research, TA assignments, grant-writing, and serving as a student committee representative for the Graduates in Neuroscience organization. I'm excited!

Vaccine Dinner Club: Simultaneous Administration of Vaccines

2009-05-11T09:36:00.001-04:00

Wednesday night, I attended a meeting of the Vaccine Dinner Club at the Emory University School of Medicine. This group of clinicians, researchers, policy makers, and other interested parties meets monthly in Atlanta to discuss issues related to vaccines. This is sort of tangential to my own research, but the May meeting theme (Simultaneous Administration of Vaccines: How Many is Too Many?) is a hot topic right now, so I was interested in hearing what the speakers had to say. Plus, they serve food and drinks. If you're in Atlanta and think this sounds like a good deal, I encourage you to click the link and learn more about the club -- it's free to join and to attend the nosh-filled meetings.

I must admit that I am a bit hesitant to make this post, because so many people have such strong opinions about immunizations these days, but I think it's important to share the kinds of things that experts talk about when they get together. This contributes to public education on the subject of vaccines, and it also lets people know that their concerns are being heard, and that medical professionals are trying to understand and alleviate them.

This month we heard from Andrew Kroger, MD, MPH, and Melinda Wharton, MD, MPH, both from the Center for Disease Control's National Center for Immunization and Respiratory Diseases. I did my best to takes notes during both talks, and I'll try to hit the key points in this post, but you should know that I'm not a doctor or a vaccine expert, so my interpretation of these lectures may be inaccurate. If I write something in error, please blame me and not Dr. Kroger or Dr. Wharton.

Dr. Kroger, a medical health educator, gave the first talk. He discussed the current vaccination recommendations established by the CDC, which cover a total of 17 different vaccines administered to children, adolescents, and adults. Because we now have the ability to protect against more diseases with vaccinations, people are getting more shots. Simultaneous administration of vaccines (which is defined as getting two or more shots during the same doctor's visit; not to be confused with combination vaccines, which consist of multiple antigens in a single syringe) is a strategy used by health care providers to ensure that people receive all of the recommended immunizations within the appropriate time frame. Dr. Kroger cited several studies indicating that giving two vaccines in one office visit is just as effective as giving them separately. In fact, it can sometimes be more effective. If vaccines are not administered simultaneously, they should be spaced out by at least one month. Giving two vaccines within the same month can lead to reduced efficacy of the second vaccine. Giving both shots at once, however, induces an immune response that is just as effective as the response to individual vaccines that have been spaced further apart. The only vaccines for which simultaneous administration is not recommended are varicella and smallpox. This is because doctors need to be able differentiate between the two diseases in the event of an adverse reaction. That is, if the shot gives you the pox (this is extremely uncommon, but possible), doctors want to be sure they know which pox you have, so they can treat it properly.

The CDC has been recommending simultaneous administration of vaccines for many years, but has added eight new vaccines to the recommended schedule since 1994. Dr. Kroger investigated simultaneous administration of these newer vaccines to see whether the historical data held true for them as well. You can find a wealth of information on this subject at the FDA's vaccine website. Dr. Kroger spent quite a while summarizing studies on new vaccines, and concluded that while we haven't rigorously tested every possible combination of shots (there are a lot of them), none of the studies conducted thus far present a contraindication for simultaneous administration.

Dr. Kroger went on to a bit of basic immunology, explaining why it's possible for our immune system to handle simultaneous vaccines. It comes down to a bit of math. Seroprotection (the goal of vaccination) is defined by antibody levels of 10 ng/mL of blood. To achieve this within a week of vaccination, only one B cell clone is needed per immune epitope for each mL of blood in the body. A typical vaccine contains about 100 epitopes for each disease that it protects against, so we need 100 B cells/mL of blood to achieve seroprotection for a disease within one week of vaccination. One mL of blood normally contains about 10 million B cells, so a healthy immune system should easily be able to handle several vaccines at once while still responding to other antigens that the body encounters.

These data left me convinced that simultaneous vaccines are effective. But are they safe? Fewer studies have been done on safety than efficacy, and there are data that indicate certain vaccine combinations can lead to a higher risk of side effects than individual administrations. Dr. Wharton, the second speaker, discussed these issues during her talk. While Googling for some of the studies she mentioned, I found this PowerPoint presentation, which is similar to the one she gave at the Vaccine Dinner Club. I suggest downloading it and looking through the slides if you're interested in this subject, as she covers more material relevant to common concerns about vaccine safety than I could possibly summarize here. The take-home message seems to be that while simultaneous vaccines may increase the incidence of side effects, these side effects are already rare, such that any additional risk caused by simultaneous administration doesn't make a huge difference. (Studies cited in Dr. Wharton's talk involved the combination of MMR and varicella vaccines. One study tracked over 531,000 children, divided into cohorts who received single, simultaneous, or combination vaccines. Only about 1% of the children across all groups were brought back to their doctor for fever symptoms after vaccination. The incidence of more severe complications, like febrile seizures, was much lower -- about 0.1%, with similar rates for sequential and simultaneous vaccines.) Parents who wish to take every possible precaution can ask their pediatrician about spacing vaccines out over several months, but this can present practical concerns for people who must take time off from work, arrange care for other children, and pay office fees during each trip to the doctor. If these issues create enough of a stumbling block, children might not be brought back for subsequent vaccines in a timely manner. And it's crucial to have children vaccinated within the recommended age range to protect them as early as possible from potentially fatal diseases. Delaying vaccination over concerns about simultaneous administration also delays protection against those diseases, so the relative risks must be balanced. While it is important to acknowledge that some children suffer unpredictable complications from vaccines, the optimal way to understand and prevent those complications is to come up with better screens for risk factors, not to simply stop vaccinating.

I thought Dr. Wharton brought up some excellent points during her discussion of risk communication with patients and parents on the subject of vaccines. Concerned parents will often reject expert opinions in favor of advice from individuals that they feel to be more caring and compassionate, even if that advice is misguided or inaccurate. It's important for healthcare providers to communicate effectively with parents, letting them know that not only do scientific studies support the importance, efficacy, and safety of vaccines for all children, but that adhering to a vaccination schedule is the best way for them to protect their child. Doctors with children of their own should be candid about their decision to vaccinate, and all physicians should make it clear that providing preventative medical care is the role of every loving mother or father. One survey of parents found that the most common concern with simultaneous vaccination comes not from spurious connections drawn between vaccines and conditions like autism, but from the additional pain and stress that children experience when receiving multiple shots. A kinder bedside manner can help with this problem, although it may be impossible to keep a child completely calm when he sees a needle coming.

The internet is teeming with discussions of vaccine safety and the dangers of the anti-vaccination movement, of course. For further reading on the subject, you can check out this article in the New England Journal of Medicine on vaccine refusal, Chris Mooney's summary of the vaccine/autism controversy in the June issue of Discover Magazine, and med student blogger Whitecoat Tales' Hard Conversations: Vaccines and Autism series.

Rotation #3 Diary: Week 7

2009-05-02T10:05:00.001-04:00

I think I lost count of rotation weeks somewhere back there... for consistency, I'll call this Week 7, but I actually have two more weeks left. Admission to PhD program in neuroscience? Check. Counting to single-digit numbers? Fail.

The sub-cloning project continues. I had one restriction enzyme digest that didn't work, so we chose a new enzyme for those samples and seemed to get it on the second try. I cut and blunted and cut and gel-purified, in between studying for my final exam and finishing my group project. These experiments lend themselves well to a crazed finals week, as I could set up a lot of reactions in an hour of lab time and just let them go overnight. Running the gels takes a while, though, as I'm working with some pretty big chunks of DNA and they are slow to separate, even on a low-density agarose gel. Outside the lab, I was proud of myself for coming up with a study schedule and sticking to it. I outlined all of the lectures, made flash cards, and got together with classmates to review material, without last-minute cramming. After taking the test on Thursday, I felt pretty good about it (although one professor did ask some really picky questions... we'll see).

I'm still waiting on the sequencing results from the mystery mice. Actually, I haven't even sent the samples to the sequencing facility yet. For some reason it's taking a long time to get purchases approved by the person managing the grant that funds these experiments, so every time I want to get something sequenced, there's a turnaround time of sometimes three days before I get the purchase order. By the time we got the funds approved for this batch, it was Friday, and no one at the sequencing facility would be there to receive our samples on Saturday, so they'll sit in the freezer this weekend and go out on Monday. One solution to this issue would be to put in a request for a really huge purchase order and reuse it many times over a couple of months, but you're technically not supposed to do this. You're just supposed to wait. Red tape is everywhere, even in the lab. Oh well.

Practiced some more stereotaxic surgeries this week. The concept seems pretty simple: anesthetize the animal, stabilize the head in the stereotax, do the procedure (in this case, we expose the skull, drill a tiny hole in it, and insert a needle into the brain to deliver our treatment), close the animal up, and let it recover (including medication for any post-operative pain). In practice, it's hard to get the head position right and adjust the arm that holds the needle/syringe into the right spot. I was constantly worried that I would do something wrong and hurt the mouse, although it was under anesthesia and felt no pain. We didn't do any survival surgeries; we sacrificed the animals immediately after injection and dissected them to check that the injection site was in the right place. Although this doesn't seem very nice to the mice, it's important to optimize the procedure before conducting the real experiments, to ensure consistent and meaningful results. This cuts down on animal use, overall. The dissection looked pretty good, so this weekend a postdoc from the lab will be doing the real experiment with some Cre virus. Once the animals recover and the virus has a chance to do its thing, we could see some interesting results. Probably this will take more time than I have left in my rotation, but I feel invested enough in it that I want to know what happens.

Although I'm just a trainee, I felt useful this week. A labmate presented some data a while ago and mentioned a weird result that might indicate a flaw with either the transgenic mouse line or with the fundamental assumption behind the experiment. When this happens, we tend to assume a technical problem first -- the mouse isn't what you think he is. Checking on this is difficult, though, because we don't have good antibodies for the protein this mouse is supposed to lack, and it's a conditional knockout, so some of its cells do have the gene and some don't (making it hard to just isolate mRNA and look for gene expression at that level). In situ hybridizations to look at the gene expression would work, but it can be hard to look at individual cells this way. Anyway, I read some papers for my last rotation where a group used laser microdissection to isolate individual cells from a brain slice, purified RNA, and then did RT-PCR to figure out if the cells were expressing certain genes of interest. I looked around and saw that Emory has a core facility that will do laser microdissection for a reasonable rate, or train lab members in the technique so they can do it themselves. We can already do RT-PCR in the lab, too. So I suggested that we try that, rather than in situs, and my labmate seemed really into the idea. I think he was already exploring this possibility with our PI, but they didn't know about the core facility. So I felt all smart and helpful for mentioning it. It's been cool to realize just how much I'm learning in grad school, and that I'm coming up with good ideas for experiments on my own. My education is working!

Now that finals are done, I have a lot of free time in my schedule for these last few rotation weeks. Then I'll be presenting my results in lab meeting, writing up a report, and choosing which lab I want to join. I might take a little summer vacation first, though...

Rotation #3 Diary: Week 6

2009-04-27T08:44:00.001-04:00

This rotation is going by in a blur! I spent Week 6 working on more sub-cloning stuff. After sequencing some plasmids and deciding which ones we wanted to use, I grew some bacteria expressing those plasmids and made maxi preps to get more DNA. This week we'll be pasting these plasmids into vectors that will later be made into lentivirus for infecting neurons. It's been really interesting to go through all of these little steps -- some projects require a lot of work before you can actually do the cool experiment that will answer your research question. The work is going a little slower than usual because I'm new to these techniques, but the postdoc I'm working with has been very patient with me. He wants to make sure that I'll get to see the end result of the cool experiments, though. With only two weeks left in my rotation, I'm not sure we'll get there in time, but I am curious to see how things go, even if we don't get there until after my rotation has officially ended.

I also collected a lot of DNA samples from some mysteriously un-genotyped mice. For a while, no one was really maintaining this particular mouse line, so we're not sure if any of these animals have our mutation of interest. I'll be making lots of DNA preps and checking out their genotype, although I've been temporarily stymied by a bad batch of proteinase K (enzyme used to digest the tissue samples before I can extract DNA from them).

Outside of the lab, things are going well. I gave my poster presentation, and people seemed pretty happy with it. (Although, one professor suggested that I be "A little less Laura" in the future -- meaning that I should, for example, avoid using colorful slang terms when characterizing mutant phenotypes. It's hard for me to be "less Laura," but it's the more professional way to go.) Also, the poster was so shiny. It's amazing how impressive my work looks when blown up to gigantic size and printed on high-gloss paper.

I have a group project due for my grad seminar this week, and I'll be taking the final exam for my Cellular and Developmental Neuroscience class on Thursday evening. I'm pretty pleased with myself right now, as I reviewed about half of the material this weekend. I have relatively light lab duties for the next few days (today I will be setting up a couple of enzyme digests and then going home) so I ought to have plenty of time to study before Thursday. If I can be strong and avoid the siren song of daytime television, that is.

Guidelines for Scientist Blogging and Online Behavior

2009-04-22T15:16:00.001-04:00

A Blog Around the Clock recently posted a draft of an institutional document governing employee blogging and social media use. This pseudonymous Big Research Institution is trying to establish guidelines about the information that its employees are allowed to share online. As someone who blogs under my own name about things that I do for a living, such policies would affect me if Emory decided to enact them. I'm posting the whole set of proposed rules in block quotes, with some of my own comments from a research blogger's perspective. I should note that this document did NOT come from Emory, and my response to it is purely hypothetical.

Social media guidelines for Big Research Institution (which I will abbreviate as BRI from here on out) staff

These guidelines are intended to cover blogs, where BRI staff discuss their projects or professional work, as well as BRI related pages set up by staff on social networking sites such as Flickr and Facebook. They do not cover any personal use of social media which is primarily about personal matters or hobbies.

I would consider my Facebook profile to be primarily centered around "personal matters or hobbies," but since it includes my university affiliation, it can be policed under this set of rules. Because nothing on the internet is anonymous, I am careful about the information that I share on Facebook, but I also get pretty personal there (sharing political links, making off-color jokes, posting pictures in which I am making a silly face, etc.). I'm completely aware of the fact that anyone can find my Facebook page and pass judgment on me because of it; what I'm not prepared to do is to act as though everything posted on my Facebook is directly linked to my job. Therefore, I would question any institutional policy that attempted to be so broad in its application to personal social networking sites like Facebook.

We have a long history of BRI staff actively contributing to public discussions. However there are a few simple guidelines for BRI staff to consider when setting up their personal blogs and wikis which are outlined under "Personal social media guidelines" at the end of this document.

Guidelines for a BRI context

BRI can clearly benefit from the use of social media to promote its activities, discuss projects and research, and increase its overall knowledge base. These guidelines are intended to ensure that BRI can have a strategic overview of how we are using social media, use it in an effective way to develop our vision, facilitate its development and cross promote where appropriate.

For the purposes of this document online social media activity by BRI staff and associates falls into two categories:

Public facing - Social media which directly relates to or discusses work or projects at BRI and has a general public audience.

Peer to peer - As above but where the blog, forum, wiki etc is used as a tool for scientists and others to communicate with their peers and is not intended for a general public audience. This includes both social media content hosted by BRI and collaborative projects.

Here again I would argue that some "public facing" content (like Facebook pages) does not directly relate to work or projects at the employee's institution, even if the employee happens to mention where he or she works.

Speak freely, but respect BRI's confidentiality and values

Whether social media content is public facing or peer to peer, the individual has a duty to:

* behave in a way that is consistent with BRI's values and policies

* respect the confidentiality of information as outlined in BRI's staff handbook

Unless there are specific concerns about the nature of the work, BRI staff are free to discuss work and research online. However, staff must not reveal any information which may be confidential. This might include aspects of research, BRI policy or details of internal discussions. Staff should check the BRI IP policy, the staff handbook and/or consult their manager if at all unclear about what might be confidential.

Before I can feel comfortable with these guidelines, I need to have "BRI's values and policies" defined. If I post pictures of myself holding a beer, or wearing a coconut bra and a grass skirt at a luau, am I somehow tarnishing the reputation of my university? If I flame someone for making a stupid post, am I considered to be doing so on behalf of my employer? If social networking sites like Facebook are to be held to these standards, do they also apply to personals like Match.com? If I were to write a lonely-hearts ad that mentioned both my employer and my participation in potentially shocking subcultures, for example, could my employer object? Those of us with any degree of internet prominence should carefully weigh the decision to make information about ourselves public, but we should do so using our own "values" as a yardstick, not a set of ambiguously-defined "values" from our employer.

I'm also uncomfortable with the idea that discussing my university's "policy" could be considered inappropriate. Shrouding institutional policy in secrecy does not bode well -- institutions with sound, sensible policies should be shouting them from the rooftops to try to attract the best employees. If my institution has a bad policy and I criticize it publicly, the proper response is not to censor me for talking about it. The response should be to improve the policy so that the institution is no longer ashamed of it.

I have no qualms about honoring confidentiality, however, or about keeping sensitive data out of the public eye. To me, that's just common sense, codified.

Editorial

The content of peer to peer pages or sites is the responsibility of the relevant department. The content should follow BRI editorial guidelines to ensure usability and accessibility. Content is the responsibility of the individual and their department and would not be edited by BRI editors. Moderation is the responsibility of the relevant department.

Public facing social media is covered by the general editorial guidelines, and should be written for the expected audience and have a moderation plan agreed with BRI.

This gives me pause. Because I have a blog that occasionally mentions my institution, I should have a "moderation plan" with them? And, what are the "general editorial guidelines" that I must follow? No blinking text? No curse words? I require more detailed information about the moderation and editorial policies in question before I would feel comfortable agreeing to anything like this. If such guidlines would entail much more than common sense policies covering confidentiality, I imagine I would find fault with them.

Intellectual property

All BRI social media output is the intellectual property of BRI.

Like heck it is. If I post one of my famously witty sonnets about DNA on my blog or my Facebook, the university doesn't get to slap it on a t-shirt and call it their own.

BRI will operate all of its social media under a creative commons license, which means that content such as images can be reused for educational purposes unless otherwise stated.

It is the responsibility of the author of any social media content to ensure that the copyright is cleared for any material published.

Ah, "for educational purposes." I don't have a problem with people sharing content from my blog -- after all, I make it freely available on the internet -- but I would like to at least be credited for creating it. It's unclear what sort of Creative Commons license is being proposed here, but I would be okay with this provided there is an attribution condition. For example, I wouldn't mind if my university linked to a post on my blog from their website, next to a picture of me, while crediting me for the writing. That does not make my blog their intellectual property, however.

Setting up of new social media and content pages

Whether you are setting up new BRI social media pages within the BRI website or on an existing social media site such as Flickr or Facebook, they need to follow the BRI interactive project process.

In the first instance please discuss with your manager. If they are in agreement then the next step is to complete and submit a concept brief for social media (link here) which outlines:

* the purpose

* the author

* the audience

* the contributors

* moderation plans

* expected duration

* how they fit with department/corporate plans

Concept brief forms are available from your manager.

This seems completely unfeasible. No one is going to consult with their manager and submit a "concept brief" before making a Flickr account. If I wanted to blog about details of experiments that were happening in my lab, I would consult with my PI before doing so. But if I just mention that I'm a graduate student in So-and-so's lab, I don't think my PI or university should have veto power over my blogging. Even if I removed all references to my PI and/or institution from this blog, any enterprising soul with access to Google could enter something like "Laura Mariani" + "neuroscience" and find references to me on my department's website. I see no need to pretend otherwise.

Existing blogs

Staff who already have a blog, wiki, forum etc. which is related to their work or BRI should discuss it with their manager and the BRI production editor. This will allow for a shared understanding of activity in this area and will help BRI promote and aggregate a body of BRI blogs in the future.

Scientists can link to their blogs from their CV's on the BRI website but it may also be appropriate to integrate it into other areas of the site and promote it more generally from BRI's website.

This seems reasonable. I think it would be cool to see a collection of blogs by Emory students, for example. Letting your supervisor know that your blog exists is one thing; making it their intellectual property or allowing them to censor what you post based on institutional "values" is another.

Personal use of social media by BRI staff

If within your blog, wiki or social media pages BRI or work at BRI is highlighted the content should comply with the Code of Conduct outlined in the staff handbook.

Additionally if a personal blog is clearly identifying the staff as a member of BRI it should have a simple and visible disclaimer such as 'The views expressed on this blog/website are mine alone and do not necessarily reflect the views of BRI.'

Personal social media pages or websites may link to BRI's website, but should not reproduce material that is available as a result of BRI employment, use any BRI branding, nor should the blog or website purport to represent BRI in any way.

If you wish to use BRI copyrighted material you need to obtain BRI's permission.

This isn't bad. As you can see, I've already included a disclaimer on my own blog stating that my opinions are my own, not Emory's, and that I don't officially represent my university. I'd be willing to maintain a reasonable Code of Conduct, but I'd have to see the handbook before deciding whether or not it was reasonable. And it's already against the rules to share confidential or privileged information that I have access to by way of my institutional login, whether through social media or some other avenue of distribution.

Social media

For the purposes of this document, the term Social Media includes:

* blogs

* forums

* networking sites such as Facebook, Bebo, Linked In

* photo sharing sites such as Flickr

* video sharing sites such as YouTube

* all other sites allowing publishing of opinion and comment where an individual might be viewed as representing BRI

Appendix: BRI's existing social networking rules

Social networking websites

We provide open access to the internet for business use. However, we do recognize that you might use the internet for personal purposes. This policy sets out your responsibilities in relation to using the internet to access social networking websites such as Facebook, MySpace, Bebo and Friendster.

Personal use of the internet

We allow you to access social networking websites on the internet for personal use during certain times. These times are:

* before and after work hours; and

* during the one-hour break at lunch.

We reserve the right to restrict access to these websites and to bar individuals who abuse our broad approach to open internet access.

Um... let's just say that I don't restrict my personal internet usage in this way. I get things done, but I also read a lot of blogs while samples are in the centrifuge. It's safe to say that rules such as the above do not apply to graduate students -- thank goodness.

Personal conduct

While we respect your right to a private life, we also have a general duty of care for the welfare of all our staff and also a responsibility to ensure that the reputation of BRI as an institution of world standing is protected. We therefore require employees using social networking websites to:

* refrain from identifying yourself as working for BRI;

* ensure that you do not conduct yourself in a way that could be perceived to be of detriment to BRI's reputation and its role as a public authority; and

* take care not to allow your interaction on these websites to damage working relationships between members of staff and clients of BRI.

Okay, this is awful. It's silly and unfeasible to require that employees never, ever mention who they work for. My neuroscience program uses Facebook groups for a lot of things, and participation requires joining the Emory Facebook network, so clearly they are not in agreement with such a policy. I think it's a bad policy for any institution. It's totally unenforceable for in-person "social networking" (i.e., going out to a bar and chatting with strangers), and it shouldn't matter for online networking, either. I'm also not a fan of "do not conduct yourself in a way that could be perceived to be of a detriment for BRI's reputation" -- what does that even mean? Rooting for BRI's rival at a football game? It's too nebulous to be useful, and just leaves the institution with an opening to reprimand employees for things they do on their own time that should be none of their employer's business.

Monitoring of internet access at work

We reserve the right to monitor internet usage, but will endeavor to inform you should your usage be under surveillance and the reasons for it. We consider that valid reasons for checking an individual's internet usage may include suspicions that you have

* been spending an excessive amount of time viewing websites that are not work-related; or

* acted in a way that damages the reputation of BRI and/or breaches commercial confidentiality.

We reserve the right to retain information that it has gathered on an individual's use of the internet for a period of 12 months.

Access to the web may be withdrawn in any case of misuse of this facility and may result in disciplinary action.

Again, I don't see this being an issue for me as a student. I'm against monitoring anyone's internet browsing habits unless there's probable cause to assume that they're doing something really bad -- and by that I mean illegal, not just unproductive. If someone's personal web browsing is keeping them from doing their job effectively, I can kind of see the argument for shutting off their access, but wouldn't it be better to just hire employees that you can trust? If it's a slow work day and someone reads the New York Times for two hours, I don't see that as a problem. Lazy people will find ways to be lazy that don't involve the internet if you take their internet access away, and people become less productive when they don't have access to useful tools, some of which are web-based.

Security and identity theft

You should be aware that social networking websites are a public forum, particularly if you are part of a 'network'. You should not assume that your entries on any website will remain private. You should never send abusive or defamatory messages.

Please be security conscious and take steps to protect yourself from identity theft, for example by restricting the amount of personal information that you reveal. Social networking websites allow people to post detailed personal information such as date of birth, place of birth and favorite team, which can form the basis of security questions and passwords. In addition, you should:

* ensure that no information is made available that could provide a person with unauthorized access to BRI and/or any confidential information; and

* refrain from recording any confidential information regarding BRI on any network

I agree with this 100%.

So concludes my fisking of BRI's proposed policy. Although I found fault with some of the items included here, I have to applaud the mysterious BRI for opening up their institutional guidelines to public discussion before setting anything in stone. It takes a certain humility for administrators to admit that their ideas might not be perfect, and I applaud them for seeking feedback from actual scientists and bloggers during the revision period.

If you have anything to add, please do so in the comments!

Bio-Tube

2009-04-21T21:38:00.001-04:00

Sandra Porter at Discovering Biology in a Digital World posted this video (embedded below) made by one of her colleagues. It shows the whole process of preparing and running an agarose gel to resolve DNA samples. This is something that I've done about a million times in the lab, but I thought it was really cool to see it in a short video. I even learned a few things! (For example, because I am woefully ignorant of all things electronic, I never actually learned which electrode was positive or negative on a gel box. I just remember "black in the back / run to the red" to keep them straight!)

After watching this educational and oddly soothing video (I've repeated some protocols so many times that thinking about them is akin to a meditative mantra), I decided to see what else I could dig up on YouTube. I actually found a playlist of 15 different videos covering SDS-PAGE and Western blots! The videos brought back unpleasant memories of those darn BioRad plates (maybe I just don't know my own strength, but I broke a lot of those little glass plates at my old lab), but the time-lapse images of gels running are actually quite beautiful, and I learned a couple of new tricks. Plus, the last video, Demystifying SDS-PAGE, is adorable. It appears to be the work of two student instructors explaining this technique to a class of bio-newbies. I was immediately won over by their dorky enthusiasm, and by their chocolate cake analogy. It made me want to go teach undergraduate bio lab!

Anyway, I thought these videos would be entertaining for scientists and interested laypersons alike. If you want to know how I spend my time in the lab, these two techniques cover a lot it.

Rotation #3 Diary: Week 5

2009-04-18T17:47:00.001-04:00

I seem to have missed a few rotation diaries -- sorry about that! Things are getting more and more hectic as the semester winds down. I had a big exam at the end of March, I've got some projects in the works for my graduate seminar, and for the past week I've also been fighting a losing battle against housework while tending to my partner, who has come down with the flu. Even so, I had time to do some things for my rotation.

My latest project has been to assist a postdoc in the lab with some sub-cloning. This I would describe as the Legos of biology -- you have all these pieces that need to fit together to make the thing that you want, and a set of rules for how the pieces can be swapped out and combined with each other. Instead of plastic bricks, we use pieces of DNA, so the end result is harder to show off to people. I've still been showing off pictures of my gels, though.

We started with some DNA plasmids that the lab already had. The goal is to snip out some useful pieces of DNA and put them into other plasmids that will be used to make a lentivirus. Then we'll be able to infect cells with the virus and make them express the genes we're interested in. (One construct is a YFP-Cre, which will allow us to knock out a gene of interest in floxed mouse brain cells near the viral injection site through Cre-lox recombination, without messing with the rest of the brain. Nifty!)

To make these new constructs, I've had to digest the DNA with a bunch of different restriction enzymes, which cut DNA in predictable places. I've also been analyzing the sequences of the plasmids, to make sure that nothing funky happened to them when we grew them up in bacteria to get the quantity of DNA that we need. So far it's been pretty good, although I had a false start with my first digestion (I made a "transcription error" in copying the postdoc's instructions into my notebook, and left out an important reagent). I also got a much lower yield than I expected after I gel-purified my digested DNA. I don't know what happened, there, since I just used a commercial kit for that step, and those things are fairly idiot-proof. I may just be an unusually talented idiot.

Currently scrambling to finish a poster for grad seminar (needs to be sent to the printer's on Monday; I finally gave a draft to my professor this afternoon...). It's my first scientific poster (not counting elementary school creations that featured a lot of construction paper), and I'm amazed at how time-consuming it can be to take things that you already have or know and put them into a new format. I spent forever tinkering with background colors and fonts and things, seeking clarity. Hopefully it'll come out all right. I put off working on it for much longer than I should have (partly my own procrastination, partly the unpredictability of life), so my goal at this point is to get it done rather than make it perfect.

First Transgenic Dog: Adorable Puppy Glows in the Dark

2009-04-11T20:14:00.001-04:00

A post on Reporter Gene describes how a team of Korean researchers has created the first transgenic dog. She expresses red fluorescent protein (RFP) in all of her cells, causing her to glow quite nicely under normal light, and even more strongly under the wavelength of light that excites RFP. The researchers named her "Ruppy," a contraction of "ruby puppy." And, I must say, she's adorable.

Above: Ruppy, the first transgenic dog. In panels b and c, Ruppy's paw is compared to the paw of a dog that does not express RFP.

"Transgenic" simply means expressing a "transgene," or a gene normally found in another organism. Transgenic mice are commonly used to study human genes in a model organism, because mice are small, easy to work with, and their genome has been well-characterized over the years. Not many other transgenic species are available. Transgenic rats are in the works in many places -- helpful because although rats may look like they're just big mice, they're actually more intelligent than their smaller rodent cousins. Transgenic rats allow us to combine powerful genetic manipulations with a wider variety of behavioral assays. Finally, some scientists at Emory have created transgenic monkeys to use in the study of neurodegenerative disease. Non-human primates may be the best way to model the human brain, and some rodent models of neurodegenerative disease don't produce the same symptoms as in humans. One reason might be that the human symptoms take many years to accumulate, and mice only have about a two-year lifespan. Transgenic monkeys may help us better understand the diseases than a rat or mouse would.

As someone who has kept dogs as pets, it's hard for me to think about using them as research animals. Beagles like Ruppy (and like my beloved pet, Teddy) are a common breed used for research because of their small size and gentle temperament (terriers are also small, for example, but they are more aggressive). While I recognize the importance of research that's been conducted in dogs, I'm not sure that I could personally work in a lab that studies them, due to my emotional involvement with the species. Happily, the use of dogs and cats in research has been declining (down by over 50% since 1979, according to the CDC), as scientists have found ways to conduct their experiments in rodents or in non-animal models. The smaller number of dogs still used for research are kept by thoughtful scientists who attempt to minimize their stress and provide them with a comfortable environment. Transgenic dogs like Ruppy will help those who still must use companion animals for their experiments develop less invasive techniques for studying these model organisms.

Hong, S., Kim, M., Jang, G., Oh, H., Park, J., Kang, J., Koo, O., Kim, T., Kwon, M., Koo, B., Ra, J., Kim, D., Ko, C., & Lee, B. (2009). Generation of red fluorescent protein transgenic dogs. Genesis DOI: 10.1002/dvg.20504

Combating Obesity with the Anti-Munchies: Are CB1 Inhibitors Any Good?

2009-04-07T11:51:00.001-04:00

In a nice bit of synchronicity, I just found a study by Dr. John McPartland in PLoS ONE examining conflicts of interest in academic medicine with respect to the cannabinoid (CB1) receptor antagonist, rimonabant (aka Acomplia). We actually discussed this drug in my Cellular and Developmental Neuroscience class yesterday, as we've been learning about long-term potentiation, long-term depression, and other forms of synaptic plasticity that can be mediated by endogenous cannabinoids. I've also been hearing a lot about conflicts of interest lately as I move through the coursework in scientific ethics that I'm required to complete. (And, of course, Emory has gotten some press about an academic physician's major conflicts of interest recently. The university is making a substantial effort to ensure that things like this don't happen again, but it's a big deal.) So, this paper seemed like a good one for me to blog about.

First, a little background on endogenous cannabinoids, or endocannabinoids. You're probably all familiar with an exogenous cannabinoid -- that is, cannabis/marijuana. More specifically, the THC found within cannabis is an agonist for the CB1 receptor, which is responsible for the majority of the drug's effects. In addition to exogenous ligands like THC, there are endogenous ligands for CB receptors found naturally in your brain, including anandamide and 2-AG.

CB1 receptors help regulate signaling in the brain. In the traditional model of synaptic transmission, the presynaptic neuron releases a neurotransmitter, which binds to a receptor in the postsynaptic neuron. Messages are sent from cell to cell, allowing for the operation of the complex network that is your nervous system. Endocannabinoids play a somewhat unusual role in this process by generating a retrograde signal -- sent from the postsynaptic cell back to the presynaptic cell. Neurotransmission causes the postsynaptic cell to produce endocannabinoids, which are released back into the synapse and bind to CB1 receptors on the presynaptic cell. CB1 activation then attenuates subsequent neurotransmitter release by the presynaptic cell (or by other cells that just happen to be in the neighborhood, if they express CB1 receptors), which decreases the strength of the synapse. This feedback balances other forms of synaptic plasticity like short-term facilitation and long-term potentiation. The endocannabinoid mechanism is also important for long-term depression (LTD), a form of synaptic plasticity that can play a role in the extinction of old memories. Some believe that this explains anecdotal accounts of short-term memory disruption after cannabis use, as overactivation of CB1 receptors by the agonist THC could detrimentally dampen synaptic strength.

The figure above shows a simplified version of the endocannabinoid system, in which glutamate neurotransmission from a presynaptic cell (top) leads to endocannabinoid synthesis by the postsynaptic cell (bottom), release of endocannabinoids into the synapse, and subsequent inhibition of further glutamate release by the presynaptic cell. Figure stolen from Prof. Randy Hall, who used it in his lecture yesterday.

Of course, LTD isn't the only mechanism of action for cannabinoids. THC is a popular recreational drug because it induces many other effects, including euphoria, relief of pain and nausea, and reduction of anxiety. It also, as any liberal arts graduate can attest, gives people the munchies. For this reason, the endocannabinoid system is a potential target for many avenues of drug development[1], but for now we'll focus on appetite suppressants.

Hunger and feeding behavior are controlled by a variety of molecules produced peripherally (for example, insulin made by the pancreas and leptin made by fat cells) and centrally (such as neuropeptide Y). Most biological functions related to feeding are centrally controlled by the hypothalamus, the brain's main neuroendocrine center. Hypothalamic cells are capable of sensing both circulating hormones and neuropeptides, allowing them to balance signals from the brain and the periphery. The endocannabinoid system plays a role in controlling hunger and feeding behavior via the hypothalamus, as described in this review by Di Marzo & Matias[2]:

[T]he brain endocannabinoid system controls food intake at two levels. First, it tonically reinforces the motivation to find and consume foods with a high incentive value, possibly by interacting with the mesolimbic pathways involved in reward mechanisms. Second, it is activated 'on demand' in the hypothalamus after short-term food deprivation and then transiently regulates the levels and/or action of other orexigenic and anorectic mediators to induce appetite.

In other words, stimulation of CB1 receptors causes animals to eat more food, and to seek out more rewarding foots (sweet or fatty) than they otherwise word. Inhibiting the action of endocannabinoids removes the preference for rewarding foods and can prevent an animal from eating, even if it has been deprived of food for some time. Other research indicates that the hormone ghrelin, which induces feeding behavior, increases endocannabinoids in the hypothalamus, and that CB1 receptor knockout mice don't have a normal appetitive response after receiving a dose of ghrelin[3].

Because of the crucial role that endocannabinoids play in hunger and eating, they're a potential target for appetite suppressant drugs. Rimonabant, which was commercially marketed as Acomplia, acts as a CB1 antagonist. This straightforward mechanism decreases appetite by interfering with endocannabinoids and their hypothalamic effects. In other words, this drug gives people the anti-munchies. But, given the broad spectrum of endocannabinoid-mediated effects in the brain, does a CB1 antagonist have other, less desirable effects? This is why we do experiments before making a new drug publicly available.

Any effective weight loss drug is a potential goldmine, and drug makers know this. Acomplia was developed by the pharmaceutical company Sanofi-Aventis and sold on the European market. During that time, Acomplia was also undergoing clinical trials in the US in an attempt to achieve FDA approval. It seems that despite some potential drawbacks to the drug, it was promoted heavily by academic physicans, many of whom did not disclose the fact that they were being paid by Sanofi-Aventis (indeed, some flat-out denied any conflict of interest when prompted) or the fact that articles being ascribed to them were probably ghostwritten by the pharmaceutical company. Dr. McPartland notes these facts in his study[4] of literature published on Acomplia during the pre-approval period.

A MEDLINE search was performed for rimonabant review articles, limited to articles authored by USA physicians who served as consultants for the company that manufactures rimonabant. Extracted articles were examined for industry-friendly bias ... Eight review articles were identified, but only three disclosed authors' financial conflicts of interest, despite easily accessible information to the contrary. The Takhar CME bias instrument demonstrated statistically significant bias in all the review articles. Biased statements that were nearly identical reappeared in the articles, including disease mongering, exaggerating rimonabant's efficacy and safety, lack of criticisms regarding rimonabant clinical trials, and speculations about surrogate markers stated as facts. Distinctive and identical misrepresentations regarding the endocannabinoid system also reappeared in articles by different authors.

To see Dr. McPartland really lay the smack down on the biased reviewers, please read his article. It goes into plenty of detail about "publication bias, which arises when pharmaceutical corporations choose not to publish unfavorable studies. ... [T]he use of unvalidated or disputed surrogate endpoints, favorable claims not supported by trial data, overstated treatment efficacy, downplayed adverse effects, lack of internal validity and external validity or generalizability, and failure to disclose financially-conflicted interests" in the Sanofi-Aventis-funded studies of Acomplia. Perhaps most damning: "[Evidence-based medicine] relies upon meta-analyses of [randomized clinical trials]. A meta-analysis of the [trials] concluded that rimonabant was safe and effective. The meta-analysis was funded by Sanofi-Aventis. ... four independent meta-analyses of the trials have questioned rimonabant's efficacy and potential for adverse effects."

Since Dr. McPartland completed his analysis of Acomplia studies, Acomplia has been taken off the European market, and the FDA rejected the drug "after data submitted by Sanofi-Aventis revealed adverse effects in RIO trials that went unreported in RIO publications, including one death in a rimonabant-treated subject (ruled a suicide by the FDA) that did not appear in the pertinent publication." It seems that chronic CB1 inhibition is not a good thing, which makes a kind of intuitive sense -- if CB1 agonists like THC make you "high," it's likely that CB1 antagonists could make you "low" (even suicidally so, if you believe the FDA's ruling). Anecdotal reports from Acomplia users in Europe suggest that while the drug effectively suppresses appetite, it also noticeably increases feelings of anxiety and unease.

Despite taking Sanofi-Aventis to task rather brutally for misrepresenting data in an attempt to sell their skinny pills, Dr. McPartland suggests that CB1 antagonists may be useful for acute conditions mediated by the endocannabinoid system, even if they are not appropriate for chronic administration. He also makes sure to declare his own potential conflict of interest: "The author previously received research and/or salary support from the Cannabinoid Research Institute, a research division of GW Pharmaceuticals."

References

1. Pacher, P.; Bátkai, S.; Kunos, G. (2006) The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacological Reviews 58:389-462. DOI: 10.1124/pr.58.3.2

2. Di Marzo, V.; Matias, I. (2005) Endocannabinoid Control of Food Intake and Energy Balance. Nature Neuroscience 8:585 - 589. DOI: 10.1038/nn1457

3. Kola, B.; Farkas, I.; Christ-Crain, M.; Wittmann, G.; Lolli, F.; Amin, F.; Harvey-White, J.; Liposits, Z.; Kunos, G.; Grossman, A.B.; Fekete, C.; Korbonits, M. (2008) The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the Endogenous Cannabinoid System. PLoS ONE 3(3). DOI: 10.1371/journal.pone.0001797

4. McPartland, J. (2009) Obesity, the Endocannabinoid System, and Bias Arising from Pharmaceutical Sponsorship. PLoS ONE 4(3) DOI: 10.1371/journal.pone.0005092

Let There Be Light: Paramecia Communicate With Photons

2009-04-05T15:46:00.001-04:00

An article in last week's PLoS ONE kind of blew my mind. I'm far from a microbiologist, but I was fascinated to read about this study on Paramecium caudatum and its ability to communicate with other members of its species by emitting photons. Even though Paramecia have no nervous systems, and are thus somewhat outside the scope of a neuroscience blog, I decided to post about this study because that's just so cool. The article, by Daniel Fels of the Swiss Tropical Institute in Basel, Switzerland, highlights previous work on so-called biophotons and establishes a protocol for testing the effect of biophoton emission in cultured single-celled organisms. Please forgive me if I muddle up the review, as this stuff is far outside my area of expertise!

So, apparently all sorts of cells can produce "ultra-weak" photons, in species ranging from plants to human beings. References in the Fels article indicate that this has been known since the 1980's, which leaves me feeling somewhat indignant that I never learned about biophotons in any of my classes. I'm going to quote the paper because it has a nice summary of previous biphoton studies (click the link to the article if you'd like to see all of the citations -- PLoS ONE is open access, so I know everyone can see the Fels paper, but reading the other references might be difficult if you don't have institutional subscriptions to their sources):

Although biophotons may carry biologically relevant information [12], [13], [22], only very little is known about whether individuals indeed use them for sending and receiving information. A few studies (with populations separated from each other molecularly but not electromagnetically) strongly suggest biophotons as transmitters of information: e.g., onion roots influence mitosis positively in neighbouring onion roots (supposedly due to so-called mitogenetic radiation [23], being probably effective in the UV-range [24]); yeast cells, which emit biophotons in the UV- and the visible range [25], affect growth in other yeast cells positively [26]; tissue cells arrange themselves in a non-random manner according to the pattern of tissue cells on the opposite side of a glass slide [27]; and germinating Fucus-zygotes probably sense biophotons emitted by their living substrate to which they direct their growth [28].

Thus, it seems that many simple cells are about to "see" photons emitted by their neighbors, and respond to these electromagnetic signals through changes in their growth patterns.

With this background, Fels decided to test the effect of putative biophotonic communication in the single-celled organism Paramecium caudatum. The experiment was simple: he cultured the Paramecia in glass and quartz containers called cuvettes -- an outer cuvette containing one culture, with a smaller cuvette placed inside it that contained another culture. The different cuvette materials allowed different wavelengths of light to pass between the cultures. He placed the cuvettes into a dark box to control for the effect of other light sources in the environment. After giving the Paramecia some time to grow, he then observed the effects of one culture on its neighbor, to see if the organisms were able to transmit information between cuvettes even though no molecular signals were able to diffuse across the barriers. Cell growth and cell division (measured by counting the total number of Paramecia in each culture at the end of the experiment) and feeding (measured by vacuole formation) were quantified, to see if electromagnetic signals between cultures could influence these simple behaviors. The study found that:

[P]opulation growth and the feeding rate of Paramecium caudatum depended significantly on (i) the presence or absence of a neighbouring population, (ii) the number of cells in the neighbouring population and (iii) the material (glass or quartz) separating these populations. The results strongly support the existence of a non-molecular information-carrying system that is based on photons.

In other words, the culture adjacent to the one being measured has an effect on the growth and feeding behavior of a group of Paramecia, and this effect is dependent on the material that separates the two cultures. Specifically, when analyzing growth, Fels saw that "large populations grew significantly better (than controls) when separated with glass from the small neighbour populations, but they grew as well as the controls when separated with quartz from the smaller neighbour populations." For feeding behavior, he reports: "When separated by quartz from a few neighbouring cells (15–20), vacuole formation was higher than for the glass units, but when separated from many neighbours (300–400 cells) it was the lowest of all treatments. The opposite effect was found for populations separated by glass." This suggests that the effects on growth were largely explained by feeding behavior -- the populations that exhibited increased growth also seemed to have a higher rate of feeding.

Are we sure that this effect is due to biophoton transmission? Not exactly. However, the differences observed between populations separated by glass and those separated by quartz would seem to indicate that at least some of the effect can be explained by the different wavelengths transmitted through those materials (glass serves as a filter for some wavelengths of UV light; quartz allows them to pass). This seems to rule out other possible mechanisms for information transfer, such as a gaseous molecular signal that diffused into the air around the cultures, or an infrared (heat) effect, as it's not likely that these would be dependent on the filtering effects of the separating material.

Interestingly, Fels reports a difference in cell growth based not only on the material separating the two cultures, but on the outer material. Glass and quartz were used to form both the inner and outer cuvettes, yet only the inner cuvette should have had an effect on electromagnetic transmission between the two cultures (the outer cuvette's job was just to keep Paramecia from spilling everywhere). The article claims that the nature of this effect is outside the scope of this study, which is a reasonable position to take, but if the cultures are interacting with the material that houses them in a way that doesn't involve biophotonic communication, this presents a potential confound for the results.

Of course, under natural conditions, single-celled organisms or cells within a single organism are not separated from each other by glass/quartz, and use a variety of molecular signals for communication. Even if biophotons play a role in cellular communication, their effects may be modulated by molecular signals (or vice versa). It would be interesting to figure out the mechanism by which biophotons are generated or received and to selectively disrupt it in Paramecia, to see if that had an effect on growth and feeding behavior between populations separated by glass/quartz or by a more permeable barrier. This would allow us to further dissect the effects of electromagnetic signaling in the presence or absence of molecular signaling, and to better understand what those crazy biophotons are really doing.

Fels, D. (2009). Cellular Communication through Light PLoS ONE, 4 (4) DOI: 10.1371/journal.pone.0005086

Yeast Geneticists, Beware

2009-04-03T08:00:00.001-04:00

...we will soon have robots to replace you.

From the video at New Scientist:

This work is normally carried out by human graduate students, but Adam has shown that robots can be just as effective researchers.

I'm getting a bit nervous.

I Got $500! I Got $500!

2009-03-31T22:22:00.001-04:00

Perhaps you remember the scene in Wayne's World in which our heroes, Wayne and Garth, decide to sell the rights to their public access TV program for the tidy sum of $5000. They proceed to dance around Wayne's basement singing, "We got five thousand DOLL-ARS, we got five thousand DOLL-ARS!" and waving the check in the air. Such was the scene at Chez Laura tonight, when I checked the page for the NextBio travel grant that I applied for earlier this month. I won! Although I only got five hundred dollars. Apparently grad students come cheap, even when compared to fictitious metalheads who live with their moms. (Oh, I kid, I kid.)

NextBio, a life science search engine, was offering three $500 travel grants to MS, MD, and PhD students. I heard about this opportunity from the Emory GDBBS mailing list, proving that it pays to read those mass emails from your department. To apply for the grant, I wrote a one-page essay about how I've used NextBio in my research -- to learn more about that, you can click the link to my essay on the NextBio grants page. While I enjoy getting money, I also find NextBio to be a useful resource (and it's even free! we all know how grad students feel about free...), so I don't mind helping to promote their product. And they're helping me attend the scientific conference of my choice with this grant, which is awfully nice of them. I'd love to go to this year's Society for Neuroscience meeting in Chicago, but we'll have to see what my yet-to-be-chosen adviser thinks of that idea ($500 is awesome, but it won't cover the entire cost, so I'll need some additional sponsorship for the conference registration and travel).

As I am but a fledgling scientist, this is actually the first grant I've ever received. I'm pretty psyched about it, and I can't wait to start looking up conferences to attend (which will be another first for me).

If you'd like to support the organization that gave me $500, or to play around with a cool search tool that is way prettier than PubMed, you should check out NextBio. You can create a profile there that's sort of like a science LinkedIn and use it to save searches and bookmarks on your favorite topics, join groups related to your field, upload projects, and do lots of other stuff. It's also a potential avenue for networking and initiating collaborations with other researchers, which is always a good thing.

If you missed out on applying for this travel grant, contact NextBio and ask them to sponsor more students in the future! After all, when they support students, the students can go to conferences, learn new things, come up with exciting research topics, publish their data, submit the data to NextBio, and the circle becomes complete.

Excellent.

Rotation #3 Diary: Week 2

2009-03-30T08:23:00.001-04:00

The second week of my rotation was much like the first -- I genotyped, I watched behavioral testing paradigms, I failed to gather helpful data. (Sigh.) Sequencing reports indicate that the two litters of mice I've genotyped are all wild-type, which makes it seem unlikely that this chimera will produce mutant pups. I'll be sequencing some more DNA from a different litter (born to a different chimera) this week, but we're not expecting much from them, either. More chimeras are in the works, so at this point it would almost be a disappointment to find a germ-line mutation in the ones we have (the money has already been spent on making a new batch!). The lack of mutants thus far delays our ability to study the in vivo effects of this mutation, though, which is really what it's all about. So, cross your fingers for my little mice.

During some of my down time this week (while waiting for PCRs to run or enzymes to digest) I went to different talks around campus. I already blogged about the Work/Life Balance Panel. I also went to a presentation in the Environmental Studies department about Gender and the Environment. I know that sounds weird, but the talks, given by Emory undergraduates in the department, were really cool. One was about Sarah Palin and how she fits into the trope of American masculinity embodied by the frontier spirit; another was about the dearth of female leadership in environmentalist organizations. The third talk was supposed to cover intersexuals (whose gender has literally been shaped by the environment, or toxins therein), but the pre-med student who was supposed to deliver it had some lab duties to attend to and couldn't come. I thought this was amusing, since I had left my lab to come listen to her talk. I only left because I didn't have any experiments running at the moment, though. I understand how experiments come to rule your life, but it's a shame that we all missed out on her presentation.

This week I have more genotyping to do, and instead of going to talks during my downtime I'll be studying for Wednesday's Cellular and Developmental Neuroscience exam. I'll be back to blogging after that.

Science Blog Gender Drama

2009-03-25T19:50:00.001-04:00

If you pay attention to the science blogosphere, you probably heard the commotion yesterday when Sheril Kirshenbaum moved her blog to Discover Magazine. She was welcomed by a bunch of sexist mouth-breathers who drooled over her appearance while simultaneously proclaiming ignorance of anything she's ever written.

Ms. Kirshenbaum has written a great post summarizing the resulting brouhaha. She articulately lays the smack down on those who make inappropriate comments about women in a professional setting, and praises the many allies who stepped up to point out that such comments are not okay. You should read her post and click on the links provided there to many other good posts on the subject.

While there were many highs and lows to "mmmmmm, wo-man"-gate, one point that I found especially intriguing was the assumption by some bloggers that the pseudonymous Comrade PhysioProf is a woman. Those who read his blog regularly are aware of his gender, but some who knew him only from his defense of Kirshenbaum's right to blog without being sexually harassed referred to him as a female. Must we automatically assume that anyone who calls someone out for sexist comments is a woman? Plenty of other male bloggers also voiced their outrage about this inexcusable behavior, and I salute them for it. I know plenty of men who consider themselves feminist allies, and I know that it can be uncomfortable for them to speak up about sexism that they witness. Thus, I would like to take this opportunity to thank these men for their contribution to the discussion, and for showing that feminism is not just a mysterious thing that happens to women when they have bad PMS.

When I started this blog, I was conflicted about using my real name and photograph on my posts. Part of this was a concern to maintain a certain level of professionalism within my university and my lab -- I don't want to spread gossip or leak confidential data. But part of it was a fear of being judged not for what I study, but for who I am. If someone reads my blog and sees content that explores issues of women in science as well as articles from issues of Science, will they think I'm whining? Will they not want to hire me, because I might be a trouble-maker? Will they perceive me as less competent because there is a picture of a young blonde woman at the top of the page? Will they be turned off because there's a tag for posts about "feminism?"

The comments directed at Ms. Kirshenbaum have given me still more causes for concern. Thankfully, most people are capable of interacting professionally with women -- even attractive women -- without making the Neanderthal-esque comments that were directed toward this female scientist through the anonymous internet. But who's to say how many people are thinking such things without saying them? I don't mean to accuse everyone who's ever noticed a cute coworker of sexism, but I do wonder about how my scientific work will be perceived as a consequence of my being born female. There are people out there who will never be as impressed by my CV as they are by my T&A, and odds are I'm going to have to work with them eventually. Thinking about this is disheartening, and leaves me feeling rather powerless.

Sheril Kirshenbaum has far more blog readers than I do, with a small army of folks who totally have her back. But, there are people who have my back, too. When things like this start to get me down, I think about my own allies: extraordinary role models, enviably talented classmates, supportive friends, and even total strangers who are enlightened enough to speak up when they see something wrong.

None of us are in this alone. And our numbers are growing.

Work/Life Balance

2009-03-24T14:00:00.001-04:00

Yesterday, I attended a panel on work/life balance sponsored by Graduate Women in Psychology, the Center for Women at Emory, and Graduate Advocates for Work/Life Balance. This informal panel served as the springboard for a discussion of women scientists in academia and how they achieve balance between career personal life.

The panel consisted of Dr. Lynn Zimmerman, Professor of Biology and Senior Vice Provost for Academic Affairs; Dr. Jessica Sales, Research Assistant Professor in Behavioral Science and Health Education; Dr. Cora MacBeth, Assistant Professor of Chemistry; and Dr. Tanja Jovanovic, Associate in Psychiatry. It was wonderful to see the breadth of academic experiences represented on this panel, and I'm thankful to each of the panelists for donating their time to this important dialogue.

Given the panel's stated focus on work/life balance, a large part of the discussion centered on the compromises one must make when juggling career and family. Three of the four panelists have children, and several of them have faced the two-body problem, in which couples comprised of two academics must find complementary job offers. They generously shared their experiences with us, providing some advice for younger women scientists who will face similar challenges in their own careers.

Because the panel was sponsored by several advocacy groups, we also discussed some of the areas in which institutional reform can lead to better support for working families. Some changes are already in progress at Emory -- for example, the Board of Trustees is soon expected to approve a measure that would allow assistant professors to automatically stop the tenure clock if they have a child (either through birth or adoption). Other goals are yet to be achieved, however. For example, some members of the panel are lobbying for Emory to draft an institutional pregnancy policy. Currently, students who become pregnant are subject to the mercy of their advisers. Professors whose students become pregnant are not bound by any university regulations for arranging family leave, exempting pregnant women from potentially risky tasks, and other issues that can arise in this situation. Other institutions have drafted official pregnancy policies to ensure that everyone is treated fairly when students become pregnant, and Emory should do the same.

Inspired by a recent post by Zuska, I raised my hand during the Q&A portion of the event to ask the panelists if they thought that the problem of work/life balance might be a bit of a red herring in explaining the dearth of women in science. After all, plenty of women in other careers have families. Why is academic science different?

Well, that's kind of a tough question, and I didn't expect anyone to shout "Eureka!" and solve everything. But I did enjoy hearing the response from the panel, which ranged from the fact that everyone's career goals are different, that people may have different family structures that aren't always forgiving of the long hours that academia demands, and that -- perhaps most interestingly -- many young female scientists come into the pipeline feeling that they absolutely don't want to pursue an academic career. While there are many reasons behind this (hostile work environments, the stressful experience of being the only woman in the room...), one point that was brought up during the discussion was that students often see their professors at the worst of times. Some professors seem like workaholic drones: slaving away in the lab, hunching over their desks, furiously writing grants, meeting deadlines, drinking gallons of coffee, and generally suffering. This makes students think, "I don't want that job!" Students may not be as aware of the benefits of an academic career, such as the job security that comes with tenure, flexible hours not often found in the corporate world, and the enjoyment that a scientist derives from doing something really cool for a living. Thus, one way to improve the number of women in academic science might be to humanize the women currently working as academic scientists. If students see their mentors as people who love their jobs, live happy lives, spend time with their families, cultivate hobbies, and occasionally switch to decaf, they might be more inclined to view academic science as an appealing career.

How can we achieve this? More faculty panels! More Emory Women in Neuroscience events! More free snacks! (...Among other things. But it's not a bad way to start.)

MicroRNAs and Mental Illness

2009-03-23T19:25:00.001-04:00

A paper published in Proceedings of the National Academy of Sciences caught my eye earlier this month. In this paper, Dr. Jannet Kocerha et al. describe the potential link between expression of a micro-RNA (miRNA) and schizophrenia. Because miRNAs are super interesting, and because I'm into understanding the molecular etiology of brain disorders, I thought it would be a good paper to blog about. Then it fell to the bottom of my Google Reader, as tends to happen when one is busy writing rotation proposals, teaching seventh grade science classes, and enjoying spring break. So, I apologize for my tardy reporting. That said, on to miRNAs!

Biochemistry fans will already be familiar with miRNAs, but it's worth explaining them as a preface to this paper because they were discovered relatively recently and tend to fly in the face of traditional biology rules. If you've taken a biology class, you probably learned about The Central Dogma: DNA makes RNA (through transcription) which makes protein (through translation). You may have also learned about the regulation of gene expression, which is a key concept in genetics. Regulated gene expression is what allows the different cells in your body to make different proteins and specialize in different functions, despite the fact that they all contain identical DNA. Depending on the cell, some genes will be turned on and others will be turned off. This allows each cell to focus on its unique function. There are several ways in which gene expression can be regulated, including transcription factors and epigenetic mechanisms. About 15 years ago, scientists discovered that certain RNA molecules can also regulate gene expression (Lee et al., 1993). RNAs that have this function are called "micro-RNAs," because they tend to be much smaller than messenger RNAs (mRNAs; the RNA molecules that carry the message used in protein translation).

miRNAs are freaky because they defy The Central Dogma. These non-coding RNAs (that is, RNAs that do not carry the sequence for translating a protein) arise from parts of the genome often characterized as "junk DNA" due to lack of association with any known protein product. It turns out that some of the "junk" is pretty important -- DNA that codes for miRNAs is essential for proper regulation of gene expression. If you mess with gene expression, all kinds of things can go wrong in a cell. If they regulate important genes, miRNAs can be critical for cellular function.

But how do miRNAs actually work? As I mentioned before, under normal circumstances, DNA makes RNA makes protein. In order for a gene to be expressed, it must be transcribed from DNA to mRNA. To make protein, the mRNA is then translated into a chain of amino acids. miRNAs work by disrupting the translation of mRNA into protein. These pieces of RNA form a sequence that is complementary to a small part of the target mRNA (in other words, where the mRNA has a C, the miRNA has a G; where the mRNA has an A, the miRNA has a U; etc.). When a complementary miRNA encounters its target, it will bind to the mRNA at the site of complementarity. This creates a double-stranded RNA, which prevents the cell's translation machinery from making protein out of the mRNA, and in some cases triggers RNA degradation.

So what does this mean? Well, it adds another possible layer of regulation for gene expression. Imagine a cell expresses Gene X. Some other process might control the expression of the complementary miRNA Y. So, in cases where Gene X is switched on but miRNA Y is switched off, Gene X leads to the production of Protein X. If miRNA Y does get switched on, though, Protein X doesn't get made -- even if Gene X is still being transcribed! All sorts of complicated feedback cycles can be created in this way, especially when certain miRNAs impact the production of other miRNAs, and on ad infinitum.

After that lengthy preface, I will now discuss the paper. Its main points and key criticisms can all be gleaned from the commentary by Dr. Joseph Coyle in the same issue of PNAS, but I will attempt to summarize the article in my own words. It's good practice for me!

Kocerha et al. were investigating a mouse model of schizophrenia in which a certain class of neurotransmitter receptor (the NMDA receptor) does not function properly. This model is based on work done in humans that has implicated decreased NMDA-receptor-mediated signaling in many brain disorders, including schizophrenia. For their paper, the researchers modeled NMDA hypofunction in several ways: they treated mice with a drug called dizocilpine, which is an NMDA receptor antagonist, and they examined mice with a mutation in a gene called Grin1, which is crucial for the formation of normal NMDA receptors. In either case, the mice exhibited "schizophrenia-like deficits" in motor behavior due to the experimental manipulations.

To identify which miRNAs might be associated with decreased NMDA receptor function, the scientists used a microarray. This technique allows us to measure whether any of a large number of RNAs are upregulated or downregulated by experimental conditions. In this case, microarray data showed that expression of a miRNA called miR-219 was significantly reduced by a single dizocilpine treatment. The researchers did not observe the same changes in mice chronically treated with dizocilpine, which is problematic because chronic treatment is considered by some to be a better model of schizophrenia than acute treatment. Still, the fact that dizocilpine had an effect on miR-219 expression made the miRNA worthy of further investigation. A similar effect to dizocilpine was seen in mice that possess a mutation in Grin1. These mice experience a 90% reduction in functional NMDA receptors that leads to locomotor behavior reminiscent of schizophrenic humans. The mutant mice were also found to have significantly decreased miR-219 in their brains.

To see whether the observed miRNA expression changes were indeed brought about specifically by the schizophrenia-like symptoms of dizocilpine treatment and Grin1 mutation, Dr. Kocerha and colleagues repeated their experiments after pre-treating the test subjects with haloperidol, an antipsychotic drug. They found that haloperidol effectively suppressed both the schizophrenia-like behaviors of the mice and the associated decrease in miR-219.

Thus convinced that miR-219 plays a role in NMDA receptor function, the researchers sought its mRNA target. Using bioinformatics, they looked for genes with RNA sequences complementary to the sequence of miR-219. One of the best candidates was CaMKIIγ, a crucial regulator of NMDA signaling. They tested miR-219's regulatory effect on CaMKIIγ by seeing whether miR-219 could inhibit the expression of the CaMKIIγ gene in cultured cells. The cells contained either normal CaMKIIγ (which has a sequence complementary to miR-219) or mutant CaMKIIγ (with mutations that made the sequence no longer complementary) connected to a reporter gene (luciferase). The reporter gene made it easy to quantify the amount of CaMKIIγ expressed in the cultured cells. These experiments showed that CaMKIIγ containing the normal miR-219 complementarity sequence was decreased by about 40% compared to CaMKIIγ that could not form double-stranded RNA with miR-219. Then, to test whether this effect was miR-219-dependent, the scientists used an antisense version of miR-219 to inhibit the reduction of CaMKIIγ. "Antisense" means the complementary sequence to the "sense" RNA that is normally found in the cell. In a way, they made a miRNA against the miRNA -- the antisense RNA binds to miR-219 perfectly, which prevents the miR-219 from binding to its complementary site on the CaMKIIγ mRNA. This antisense experiment restored a significant amount of CaMKIIγ expression, providing evidence that CaMKIIγ expression is indeed inhibited by miR-219. These results were further confirmed by measuring endogenous CaMKIIγ protein in cortical neuron cultures made to overexpress miR-219 and seeing a reduction in CaMKIIγ compared to controls.

Then came some really exciting stuff. After showing that miR-219 and CaMKIIγ interact in vitro, Kocerha et al. wanted to see if they could improve the schizophrenia-like symptoms of their mouse model by treating them with antisense miR-219. After infusing the brains of dizocilpine-treated mice with this miR-219 inhibitor (a tricky technique to master, because RNA degrades so easily), the team observed "markedly altered hyperlocomotion and stereotypy 30 min after dizocilpine administration ... when compared with mice receiving the LNA mismatch or saline." The mice treated with antisense miR-219 had less pronounced schizophrenia-like motor symptoms, although the effect of the drug was not completely eliminated. This seems to indicate that a significant portion of the behavioral effect of dizocilpine is mediated by miR-219.

Of course, we should take such experiments with a grain of salt, especially when animal models are being used to represent a complex psychiatric disorder like schizophrenia. Dr. Coyle points out one especially intriguing point in his commentary in PNAS: "It seems counterintuitive that reduction in miR-219 appears to be responsible for hyperactivity in the acute dizocilpine paradigm but reducing miR-219 levels with antisense infusion reverses dizocilpine-induced hyperactivity." Hopefully further research will be able to explain this apparent inconsistency. As for the broader implications of this study for schizophrenia patients, it's difficult to assess whether mice are experiencing hallucinations or mood disorders, so all of the results observed here are based on the motor symptoms of decreased NMDA receptor function (hypermobility, stereotyped repetitive movements). We already have drugs that can mimic the beneficial effect of miR-219 inhibition in these animal models, so at this point no one is advocating RNA interference as a potential treatment for psychiatric patients. This research does show a new mechanism by which schizophrenia symptoms and the drugs that relieve them may be interacting, however, which could lead to new avenues of drug development as we further elucidate the players in this biochemical pathway.

For those without subscriber access to PNAS, other reviews of the paper can be found at The Scripps Research Institute and Schizophrenia Research Forum.

References

Lee R.C., Feinbaum R.L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5): 843–54. (1993) DOI: 10.1016/0092-8674(93)90529-Y

Kocerha, J., Faghihi, M., Lopez-Toledano, M., Huang, J., Ramsey, A., Caron, M., Sales, N., Willoughby, D., Elmen, J., Hansen, H., Orum, H., Kauppinen, S., Kenny, P., & Wahlestedt, C. MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction Proceedings of the National Academy of Sciences 106(9): 3507-3512 (2009) DOI: 10.1073/pnas.0805854106

University Budget Crises: Who Suffers?

2009-03-22T13:01:00.001-04:00

The article that inspired this post doesn't directly affect me, since I'm currently a fairly well-funded graduate student at a private university in Georgia. But I think the topic of university budget crises brings up a lot of points that are universal. Universities around the country (including my alma mater) are facing budget cuts and hard choices about how to restructure themselves in this economic climate. Thus, I thought this was worth writing about.

I spent part of my spring break this year visiting my hometown of Gainesville, FL. While I was in town, I read this article in the local newspaper about one way in which the University of Florida is trying to adjust its budget. UF, like most educational institutions in Florida, was having financial problems even before the current economic downturn, and they're in for some hard times. I was accepted by a graduate program at UF, but I decided not to attend for several reasons, one of them being the blatant disregard for education funding that the State of Florida seems to have. And I was especially disheartened to read about UF's decision to cut back on undergraduate programs in education and nursing to compensate for some of these financial woes.

The college might still admit undergraduates but have the expectation that they would continue their educations by entering graduate school, [College of Nursing Dean Kathleen Long] said. The college plans to phase out master's degrees, so nursing students would eventually be expected to get doctorates, she said.

Undergraduate students in early childhood and elementary education programs already are asked to take a fifth year to earn their master's degrees. College of Education Dean Catherine Emihovich said the undergraduate programs might admit fewer students while others would need to take other routes that required even more graduate classes.

At a time when Florida is experiencing a shortage of nurses and qualified teachers in many subjects, the largest public university in the state will require students to take more classes before entering the workforce. I can only assume this is because they will be guaranteed more tuition money and more cheap graduate student labor by asking the students to stay in school longer. (Some students are offered scholarships, but graduate programs in nursing and education are not as generously funded as PhD programs in the life sciences.) Even so, how does it make sense to force such changes on the programs that produce much-needed nurses and teachers? Wouldn't it be a better idea to focus on departments that are less vital to meeting Florida's needs in healthcare and education?

Especially reprehensible is this theory:

[Education professor Dorene Ross] questioned why education and nursing, which have mostly women students, were targeted for possible elimination. In 2008, undergraduate nursing had 98 percent female students and early childhood and elementary education had 95 percent female students.

"There is a question whether these programs are being targeted ... because there will be less push back," Ross said.

Say it ain't so, UF. Consider this post to be just one drop in the many bucketloads of "push back" that you will incur if this turns out to be true.

Rotation #3 Diary: Week 1

2009-03-21T16:26:00.001-04:00

A new rotation brings a new series of blog posts! I finished my first week today, and I think things went well. I started off pretty helpless, as is the case with any new lab position. It's interesting to see how different labs perform common tasks like PCR and westerns, because everyone has their own favorite reagents, special protocols, and secret tricks for optimizing the results. Once I learned some of this lab's quirks, I was set free to start doing my experiments.

I started off genotyping mice. Woo, thrilling. But, I'm actually quite interested in what the results will be (I should know on Monday, when my sequencing data comes in). The lab is generating a new line of mice, and I'm testing the first litters born to a couple of chimeras. When making genetically engineered mice, you have to start with regular mice and make these blended embryos from normal mouse cells and mouse cells that you have messed with. If these embryos survive, they grow up to be chimeras (usually you choose mice of two different colors, so that the chimeras will be obvious because they come out all patchy). Then you have to hope that at least some of the germ cells (eggs or sperm -- the chimeras are normally male, but we have one female, who is probably XO rather than the normal XX due to some quirks of the mouse-making process) from those chimeras are mutant cells, so that they will produce offspring that contain your desired genetic modification. If you don't get any germ-line chimeras, you have to make more chimeras, which quickly gets expensive. So, we have a vested interest in seeing if these baby mice are mutants or not.

Thus, I did some PCRs, then purified my PCR product and sent it off for sequencing. Apparently this is easier, more reliable, and perhaps even cheaper than doing an enzyme digest to see whether my mice are mutants or not. (The mutant gene contains a restriction site that isn't found in the normal gene, thus if you digest the DNA with a restriction enzyme, the mutant DNA is cut into two pieces while the wild-type DNA remains whole. You can see the different sized pieces of DNA if you run them out on a gel.) It costs about $8/sample, which seems ridiculously cheap to me. Of course, I'm only sequencing an amplified piece of DNA that's around 300 base pairs long. For reference, your genome is a million times bigger than that -- that's three billion base pairs. And I would not pay $8 million to have my genome sequenced. So, it might not be such a great deal, after all...

In between my genotyping experiments, I got to learn some new mouse-related skillz. This lab identifies individual mice with numbered ear tags, which I have not used before. To tag the mice you use a little pliers-type thing that punches a small metal tab through the ear flap and puts the tag in place. It's basically like getting your ears pierced by the piercing gun at a Claire's in the mall. I had never done this before (previous labs used toe-cutting -- which is pretty barbaric, but it's the only way to ID very small newborn mice -- and ear punches). So, I got to practice tagging a few mice. I have to say, they seem much more upset about being picked up and gently restrained than they do about having their ears pierced.

The lab also does a fair number of behavioral assays, which I have no experience with. On Friday, my labmates were testing a drug treatment on some of the mice, so I got to watch them administer the drug and give the mice a behavioral score reflecting the severity of the drug's effects every 10 minutes. It was pretty interesting, but I can see how it would get old after doing it over many trials. Since you're observing every 10 minutes, it would be hard to get anything else done during the trial, and staring at mice is not the most fun thing in the world. A video recording system would allow the experimenter to walk away during the trial and review the film later (with the added benefit of blinding the experimenter to the amount of time elapsed since drug administration, if the film could be chopped up into segments and rearranged), but since this system is intended to be high-throughput, they just suck it up and spend a few boring hours running lots of mice as needed.

So far, so good. Everyone in the lab has been really friendly to me, and they seem like a fun bunch of people. Plus, we get free lunch at lab meetings! (This is a crucial point to consider when choosing a lab.) Mouse work is not my favorite thing, as maintaining a mouse colony gets tedious (not to mention smelly), but the mouse is a pretty good model system if you want to do clinically relevant research. I may have to just resign myself to the task.

More updates next week!

Brain Awareness Week

2009-03-12T11:48:00.002-04:00

Yesterday I spent the morning and part of the afternoon teaching seventh graders at Sutton Middle School about neuroscience as part of Brain Awareness Month. A classmate and I partnered up for this outreach activity, which required us to create a lesson plan that met Georgia Performance Standards for Science and covered some of the Society for Neuroscience's Core Concepts. We chose to talk about neurotoxins, specifically those found in some poisonous species of native Georgia wildlife (the Eastern coral snake and the black widow spider).

My partner (fellow first-year neuroscience Ph.D. student Karen Murray) and I worked together to design our lesson. I made a PowerPoint presentation that covered the basic concepts of neurons, synapses, and the neuromuscular junction, as well as neurotoxins and their effects. Karen created a worksheet that contained questions for the students to answer as they listened to our lesson, as well as some more in-depth "thinking questions" to do for homework. We also collaborated to design an in-class activity in which students acted out synaptic transmission at the neuromuscular junction by throwing Jolly Rancher candies (representing the neurotransmitter acetylcholine) into decorated shoeboxes (receptors). I've uploaded the PowerPoint presentation to my Emory webspace and created a globally-accessible Google Documents version, as well. (The Google version contains some errors caused by the change in file format, and it doesn't include additional the notes I made for each slide in PowerPoint.) If you're interested in using any of this material for a similar activity, please let me know and I'd be happy to send along all of my notes.

Overall, I think the lesson went quite well. The kids seemed engaged and attentive. We tried to do a lot of interactive teaching -- asking the kids what they thought "neuroscience" was before we defined it ourselves, helping them to break down tricky words like "neurotransmitter," and constantly reinforcing the material we had just covered ("So, the neurotransmitter at the neuromuscular junction is called acetylcholine. And which cell has the neurotransmitter? Is it the neuron, or is it the muscle cell?"). I think this teaching style paid off, because by the end of the lesson all of the students had filled out their in-class worksheets perfectly. We also structured the lesson such that every ten minutes or so, we were acting out neurotransmission under different conditions (normal, in the presence of coral snake venom, and in the presence of black widow spider venom). Getting out of their seats and watching their classmates act a bit goofy (we had one student play the muscle in each skit, and they were great at flexing their biceps and doing their best bodybuilder impressions) seemed to keep the students entertained, and we never spent long blocks of time just lecturing.

Here I am in the classroom, talking about neurotoxins. (I've cropped out Karen, in case she doesn't want silly pictures of herself on the internet. I've also cropped out students who were facing the camera or in profile; hopefully the parents of the students pictured won't be upset that I'm showing the backs of their heads here. If you are such a parent, please contact me.) I was impressed with the questions that students came up with on this subject, like "Why does a black widow spider need to use a neurotoxin to catch its food?" I'm not sure anyone knows the definitive answer to that question, so I talked about how different animals have evolved different strategies for survival, and this spider happens to use venom as a strategy. We talked about other strategies that predators use, such as being bigger, faster, and stronger than their prey (like a lion). Perhaps using a neurotoxin to catch prey allows the spider to devote less resources to being big and strong and more resources into things like making baby spiders.

We also got some great questions about the kinds of jobs a neuroscientist can do (I explained the different between neuroscience and neurology/neurosurgery -- we're not medical doctors, although a lot of us do research on clinically relevant subjects). One student even came up to me after class and said that he wants to be a scientist and would love to learn more about what it's like to do scientific research. I talked to him for a few minutes and encouraged him to email me if he had any more questions. My heart pretty much melted at that point. But then, another student came up to me after class and asked if he could buy some Jolly Ranchers off of us! I guess they can't all be future scientists.

I had a great time doing this outreach activity, and I would definitely go back to public schools in the future. Several students asked if we go to lots of other schools talking about neuroscience, and we explained that this was our first year in the neuroscience program and thus our first time participating in Brain Awareness Month. I hope that the questions we got about this imply that students couldn't tell that it was our first time, and thus that we did a pretty good job. All in all, it was a great experience for me, and hopefully for the students, too.

Psychedelic Medicine

2009-03-04T13:43:00.001-05:00

I received an email this afternoon with the subject "2-book set: Psychedelic Medicine," from an email address I didn't recognize. I wasn't sure what this referred to, at first, but my spam filters are pretty good; unless a mysterious message mentions H3RB4L VI4GR4 in the subject, I usually read it.

The email turned out to be from Dr. Thomas B. Roberts. He included some information about his book Psychedelic Medicine: New Evidence for Hallucinogenic Substances as Treatments, and a line suggesting that I might like to request a copy for my library. I can only assume that he discerned my interest in the subject from my post about DMT's action on the sigma-1 receptor, which reviews the recent article by Fontanilla et al. on a newly-discovered role for hallucinogens/entheogens in the brain. Because there was little information in the email not related to promoting the book, I did feel a bit spammed. However, I doubt that these emails are sent out in mass quantities to people who haven't indicated that they would appreciate more information on psychedelics. So I decided to post about it, in case some of my blog readers (all seven of you, according to Blogger's subscriber statistics!) would be interested.

I haven't actually seen Dr. Roberts' book, but the table of contents makes it seem like informative reading that would be suitable for non-scientists. I don't feel right asking my library to buy the book, given that I'm not doing any real research on hallucinogens. But, if you liked my previous post and want to learn more about how these drugs can affect the brain, you might want to track down a copy.

Book Review: Microcosm

2009-03-02T18:07:00.001-05:00

Microcosm: E. coli and the New Science of Life by Carl Zimmer

Rating: 4 of 5 stars

I'm a big fan of Carl Zimmer. His blog, The Loom, is a great way to keep up with the latest scientific developments in words that a layperson can understand. His other books (I've read Parasite Rex, At the Water's Edge, and Soul Made Flesh) have been quite good. His newest book, on the bacterium E. coli, was also an enjoyable and educational read.

I find I get the most out of science writing when it's on a subject outside of my expertise. I loved Parasite Rex for this reason, because parasitology, despite being utterly fascinating, is often overlooked in general biology classes. I'm training to be a neuroscientist, so I don't really study bacteria (although, they are handy when I need to produce vast quantities of DNA for use in experiments on organisms that actually have a nervous system). Therefore, I learned a lot from this book about the complicated genetic circuits that can exist in such a simple organism.

I knew some basic facts about E. coli from my genetics classes (operons, phages, plasmids, bacterial sex...), but I had never studied the mechanisms by which the germ senses chemicals in its environment and chooses its method of locomotion accordingly. These little bacteria, with only the most rudimentary of sensory organs, manage to locate food sources and move toward them, or move away from noxious chemicals. This is really pretty amazing when you think about it. I mean, I have a fully functional brain and have still been known to accidentally drink sour milk. The bacteria also form complicated bacterial "cities," called biofilms, in which they seem capable of cooperation and even altruism, sacrificing themselves for the good of the colony. All this, without so much as a nucleus! They are some pretty impressive little cells.

The little details about scientists that get thrown into this book really add a lot of flavor to the potentially dull retelling E. coli biology's history. People writing "Hooray!" in their notebooks when an experiment works, husband-and-wife teams cracking the genetic code of bacteria, experiments testing just how long an E. coli colony can live that span multiple generations of researchers... these touches make the stories seem more real to me. I can picture the labs, the distinctive red graph paper notebooks, the begloved grad students. I can almost smell the Luria broth.

Some of the later chapters tackle genetic engineering and synthetic biology, both hot-button scientific issues with E. coli inspiring their biggest advances. While Zimmer covers some of the controversy, I would have enjoyed more discussion on this, and perhaps a little less of the basic genetics that I already knew. I'm a pretty specialized reader, though, and can appreciate how important that background knowledge is if one isn't already a biologist. I can also appreciate that the book should not be allowed to grow indefinitely long, and debating the ethical issues in full detail is probably a book in and of itself.

Overall, I'd say that Microcosm makes enlightening reading for anyone who's already a biology enthusiast, but perhaps might be a hard sell for non-bacteria fans. I still think Parasite Rex is Zimmer's most jaw-droppingly fascinating book (perhaps because parasites can become so creepily entwined with brain function -- I love that stuff!), but I'd probably rate this one as his second best. Give it a read, why don't you?

(Cross-posted from my GoodReads page. View all of my book reviews.)

Rotation #2 Diary: Week 8 (It's Over!)

2009-02-28T11:41:00.001-05:00

The last week of this rotation contained many ups and downs. On the positive side, I produced the most beautiful western blot I've ever seen. My tricky protein finally behaved, and I was able to detect nice, sharp bands in most of the samples I tested. I was so excited! I showed the postdoc who's been helping me, and she was also excited. I showed my adviser, and she was pleased. Yesss! I am a western blot queen! All I had to do was repeat the experiment two more times, and I've have some quantifiable data.

Well, you know what they say about the best-laid plans of mice and scientists... I ran the gels again and the new blots looked like crap. I wasn't able to get any signal from the samples that had behaved so beautifully the previous day. I'm told that this is a common problem that people in the lab have with this protein. We hypothesize that perhaps the protein doesn't like freeze/thaw cycles, and thus it only shows up when freshly made protein lysates are used. That's pretty annoying, since I get about one mL of protein lysate from each mouse tissue, but only use 10-50 µL for each gel (thus, each tube of protein lysate should be enough for 20-100 experiments!). One potentially easy way to solve this problem, if it is a freeze/thaw thing, would be to aliquot my fresh protein lysates into 20 individual tubes, instead of one big tube, so that I'd only thaw what I need for one experiment at a time. Doing this is somewhat annoying, but if it preserves my ability to get beautiful western blots, it's worth the trouble. However, with my rotation now over, I don't have time to spend three days making another set of lysates, aliquot them, and try again. Instead, I will be creating a rotation report based on very little actual data. My methods section will be long, though -- I tried a lot of different things to make this protein cooperate with my experiments. A few of them kind of worked. I can document that.

I start my third (and probably final) rotation on March 16. No more rotation diaries until I start working there.

Who's the Scientist?

2009-02-26T08:26:00.001-05:00

I can't recall what chain of links initially led me to this website, but I'm so glad that I found it. It collects the drawings and descriptions of scientists made by a seventh grade class both before and after a visit to FermiLab. In addition to being absolutely adorable, these creative projects give us a sense of the popular conception of what a scientist is, and how it may differ from what real scientists are like. I was heartened to see that while many kids drew a stereotypical bald white guy as their "before" scientist, some of them knew going into this project that scientists can be, for example, women. The white lab coat was fairly universal, though. I guess kids don't know how lax we are with our PPE. (They also seemed excited to learn that real scientists wear casual clothes to work. Examining the photo of the class will show that they're wearing school uniforms, and apparently are not big fans of the restrictive dress code.)

This web discovery is especially appropriate given that I will be doing some outreach with seventh graders myself. As part of our first-year graduate seminar, Emory neuroscience students will be participating in Brain Awareness Month this March. I'm working with a partner to design a lesson for a middle school class. We'll be teaching about the neuromuscular junction, and how some native Georgia species produce toxins that affect this synapse. (Coral snakes have a curare-like toxin in their venom, which blocks acetylcholine receptors in the muscle cell. Black widow spider venom, on the other hand, induces the nonspecific release of acetylcholine. Both of them can mess you up.)

I think it would be great to have "my" seventh-graders do this exercise. I've already been matched with a local teacher for Brain Awareness Month; I may have to contact him and see if he's into it. Ideally, I'd then get to take some of the drawings home and put them on my fridge. I'll be sure to post again after my classroom visit, and let you all know how it goes!

Compound Mutants: A Better Model for Autism?

2009-02-23T21:45:00.001-05:00

Dr. Mriganka Sur and colleagues at MIT's Picower Institute for Learning and Memory published a paper in Proceedings of the National Academy of Sciences earlier this month on a compound mutant mouse model of brain enlargement and abnormal social behavior. Both increased brain size and social deficits are hallmarks of autism spectrum disorders (ASDs), a very hot research topic these days. The paper shows that these mice, which have mutations in two genes called Pten and SLC6A4, exhibit some of the characteristic symptoms of ASDs. The key finding is that the combined mutations exacerbate the mices' symptoms, such that a double mutant exhibits more severe problems than a mouse with mutations in Pten alone or SCL6A4 alone. From this, the authors conclude that these two ASD candidate genes play off of each other during development, providing further evidence that while there is no single "autism gene," combined genetic risk factors seem to play a large role in the disease's etiology.

Pten and SLC6A4 were already known to play individual roles in ASDs and other neurological disorders. Pten is a regulator of a highly complex series of interlinked biochemical processes called the PI3-kinase pathway. This pathway regulates a huge number of cellular functions, including cell growth, differentiation, proliferation, and survival. Because of this, the pathway is closely linked to tumor formation -- indeed, Pten is found to be absent in many kinds of tumors. But aside from its role in cancer, Pten seems to help regulate normal brain development. One effect of Pten disregulation is macrocephaly -- fancy science language for "big heads." This molecule may be required to keep brain growth in check. Relatedly, a subset of individuals with autism and other forms of cognitive impairment are haploinsufficient for Pten, meaning that they carry one normal copy of the gene and one inactivated mutant copy. Macrocephaly is commonly associated with ASDs, and this may be one reason why. (TSC1 and TSC2, the genes that cause tuberous sclerosis, are found in the same pathway. Tuberous sclerosis, it's worth noting, is a tumor-forming disease that is also the most common comorbid disorder with autism.) People with Pten mutations display a broad range of symptoms, however -- some are far more impaired than others. For this reason, the gene has been suggested to sensitize individuals to the effects of other mutations, which in turn establish the severity of cognitive impairment in these patients.

Meanwhile, SLC6A4 is a gene that codes for a serotonin transporter. The protein made by this gene helps to regulate levels of serotonin in the extracellular space. One common biological marker for ASD is an increase in peripheral serotonin levels, so it seems that there is some association between autism and the regulation of this key neurotransmitter. In addition, some patients with ASD have been found to carry a mutant SLC6A4 allele which greatly reduces the transporter's expression. These patients, like individuals with mutant Pten, tend to have overgrown brains and some form of social impairment.

Previous research had made some associations between the PI3-kinase pathway and the serotonin pathway in vitro -- studies of protein-protein interactions and protein expression in cultured cell lines. Dr. Sur's study, however, makes the first direct link between PI3-kinase/serotonin pathway interaction and ASD symptoms in vivo. By breeding together two mutant mouse lines -- a Pten heterozygous knockout and a SLC6A4 loss-of-function line -- the researchers were able to study the combined effect of these two mutations in a living animal.

Both Pten and SLC6A4 single mutants had previously been shown to exhibit macrocephaly. When you combine the two mutations, though, the mice develop brains enlarged more severely than those of mice with individual mutations alone. The biochemical mechanisms allowing these genes to cause brain overgrowth have not been completely explained, but it seems that they are acting on different but related cues in brain development. I was unable to tell from the published figures whether the brain size increase in the compound mutants was greater than the sum of the increases of the two individual mutants, however. It's possible to imagine a situation in which the two genes were acting on completely unrelated pathways that could still cause an additive effect in the compound mutant. Just as a simplified example, we might someday learn that Pten regulates overall cell size, whereas SLC6A4 regulates the pruning of superfluous neurons during development. If this is the case, then you'd expect that combining the two mutations might lead to brain size greater than that seen in either of the single mutants (because then you'd have too many cells and the individual cells would be overgrown). A more convincing link is established if you prove that the change in brain size is somehow worse than would be predicted by the effects of the individual mutations. I wish this paper had provided more explicit measurements for the brain size experiments, to allow for this sort of comparison. Still, the study indicates that the compound mutant displays a more pronounced ASD-like phenotype than either individual mutant, which, combined with the combinatorial mutation theory of ASD, makes these mice an interesting model.

After measuring macrocephaly in these mutant mice, Dr. Sur and colleagues examined their behavior. ASDs are primarily diagnosed based on behavioral deficits, so it's important to establish whether the social behavior of an ASD mouse model is affected by the experimental manipulations being performed. The experiment used a fairly standard test of mouse sociability, in which the mice are given a choice between spending time in a chamber with an unknown "stranger" mouse (defined as the "social" chamber) or a novel inanimate object ("nonsocial" chamber). Most normal mice prefer to spend time getting to know a new mouse than playing with a new object. The Pten single mutant mice did show a deficit in this social behavior assay, spending roughly equal time in each chamber rather than showing a preference for social interaction. The SLC6A4 mutants also showed a decreased preference for the "social" chamber when compared to normal mice, although the effect was not statistically significant. Compound mutants, meanwhile, showed a social deficit more pronounced than that of either of the single mutants. This result seems to confirm the additive effect of the two mutations implied by the brain size measurements.

Other tests of social behavior, including social approach/avoidance and social recognition, also found deficits in socialization among the mutant mice. A test of prepulse inhibition, however, which measures the sensitivity of sensory and motor systems that can be disrupted in ASD patients, did not show an additive effect in the compound mutants. The researchers theorize that the two genes studied here are therefore involved in brain development relevant to social behavior, but not necessarily involved in other ASD symptoms such as sensory and motor defects. For a disease like autism, which involves symptoms in many different systems, this is not an unreasonable theory to espouse.

In the discussion section of their article, Dr. Sur and colleagues propose a few mechanisms by which the serotonin and PI3-kinase pathways could interact in ASD patients. Perhaps Pten is directly affecting the serotonin pathway by binding to serotonin receptors:

One possibility is that Pten and serotonin receptors may physically interact in a regulatory manner to influence brain development. In neurons, Pten binds the 5-HT2c [serotonin] receptor and, via its phosphatase activity, limits agonist-induced activation of this receptor and modulates the firing rate of dopaminergic neurons in the ventral tegmental area. It is interesting to note that 3 drugs that have been reported as alleviating symptoms of autism -— the atypical antipsychotics risperidone and olanzapine and the antidepressant fluoxetine -— all have antagonistic effects on the 5-HT2c [serotonin] receptor, in addition to well-known effects targeting other members of the serotonin and dopamine pathways.

Alternately, serotonin signaling might regulate the PI3-kinase pathway, as has been implied by several tissue culture experiments. Either theory could provide a mechanism by which the two pathways interact to regulate neuron growth, development, and function in a manner that might explain some ASD symptoms. They posit that the interaction between these two pathways could provide new therapeutic targets for treatment of ASD, allowing development of new drugs that ameliorate both abnormal cell growth and dysfunctional intercellular signaling.

Regardless of the exact mechanism, this study shows that a combination of genetic factors can be used to create a better animal model of ASDs. The scientists go on to discuss the fact that Pten dysfunction may increase susceptibility to spontaneous additional mutations and deleterious effects of environmental toxins in haploinsufficient patients. They propose using Pten mutations in combination with other genetic and environmental perturbations to further elucidate the role this gene may play in enhancing ASD symptoms in the presence of additional risk factors. If this line of research pans out, we may learn that while autism has no single genetic cause, there may be certain genes that greatly increase the effect of other risk factors that have yet to be fully characterized. If genes like Pten are responsible for increased sensitization to other mutations, they may provide a single target for treatment of a multifactorial and poorly-understood disease.

A press release from the Picower Institute has more information about this study.

D. T. Page, O. J. Kuti, C. Prestia, M. Sur (2009). Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior Proceedings of the National Academy of Sciences, 106 (6), 1989-1994 DOI: 10.1073/pnas.0804428106