Crowdfunded, open source PCR machine now available!

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"

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!

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

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!

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?

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

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 Cincinnati. 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