Fly Neurobiology Meeting, Redux

So I just got back from the fruit fly neurobiology meeting at Cold Spring Harbor Laboratory. It was a week filled with posters and talks, reunions and awkward introductions, wine and lobster, disco balls and a dance party reminiscent of your high school prom.

After the last meeting two years ago I wrote all about what this quirky fly extravaganza is really like (posted here), so I didn’t think I’d have much more to say after this one. But I was wrong—not only is every meeting unique, but your personal experience is always different depending on what career stage you’re in, what you’re working on, how your research is going, how many people you know, and a million other things. So today I’ll recap my thoughts from this year’s fly neurobiology meeting.

Flies on the prize

One difference this year was the ongoing celebration of the Nobel Prize in Physiology or Medicine, which was just awarded to three fruit fly researchers, Jeffrey Hall, Michael Rosbash, and Michael Young. These scientists were recognized for discovering the molecular mechanisms that control the circadian rhythm, which is your daily internal rhythm that makes you want to go to sleep or wake up at certain times of the day. One of my first blog posts actually covered this exact topic and how it was first discovered in flies; read here if you’re interested.

It’s always cool when fruit flies get the Nobel Prize. (Ok, I guess the flies themselves didn’t actually get it, though they sure deserve it). But I think this time a lot of us were extra excited because the work being recognized falls within the field of behavioral genetics, a field that is well-represented at this meeting. Behavioral genetics refers to the study of how genes influence behavior, and fruit flies are currently a widely used model system in this field. But it wasn’t always so.

Starting in the early 1900s, fruit flies were greeted warmly as a model for studying the structure of genes, how cells work, and the processes that control the physical development of an animal. They were treated with much more hostility, however, as a model for studying animal behavior. After all, a fruit fly doesn’t behave anything like a human, does it?

Actually, many aspects of behavior are conserved between flies and mammals (yes, even humans), as are the molecular and neuronal mechanisms underlying these behaviors. The scientist who founded this field of behavioral genetics was Seymour Benzer, who believed mutant flies would allow him to identify specific genes that influence particular behaviors, like learning, navigation, and circadian rhythms. People were extremely skeptical that flies could be used to study behavior at all, let alone whether individual genes could be shown to play a specific role. Benzer’s own mother couldn’t believe that her son could make a living by studying the brains of fruit flies; she suggested that he have his own brain examined instead.

Seymour Benzer with a fruit fly model (credit: W. A. Harris, PLoS Biology)

But Benzer persisted. He and his student Ron Konopka analyzed the behavior of hundreds of mutant flies, monitoring which times of day they were active. They found that flies have a 24-hour circadian rhythm, just like humans. And by isolating mutants with abnormal rhythms, in 1971 they identified the first gene controlling circadian rhythms, which I believe was also the first gene shown to affect ANY kind of behavioral response.

This gene, period, turned out to be a core component of the molecular clock. The work of Hall, Rosbash, and Young built upon this finding and elucidated the elegant mechanism by which molecules in your cells tell time (summarized here).

Today thousands of fruit fly researchers, including myself, can trace the origins of our work back to Benzer and his lab. All of us who are studying the behavior of tiny fruit flies, recording their minute actions, attempting to uncover the underlying mechanisms in the brain—we all owe our livelihoods to Benzer’s creativity and determination, as well as the people who continued and extended his work. Although Benzer died in 2007 and never won a Nobel Prize, it was clear at this meeting that most of us feel this prize is a long-overdue recognition of his continuing legacy.

Experience counts

Aside from the pervasive exuberance about the Nobel Prize and the exciting new science that was presented, this meeting felt a bit different for me. For one thing, this was my 5th Neurobiology of Drosophila meeting and my 8th or 9th meeting at Cold Spring Harbor. When I first came to this meeting, I was overwhelmed by all the science and felt like I didn’t know anything or anyone. Now it almost feels like home.

As you might guess, I’ve learned a few things about attending Cold Spring Harbor meetings. I have all kinds of useful knowledge, like where to meet the shuttle at the train station, the train station’s secret ticket booth, running routes around campus, which bathroom locations have the shortest lines, what time the bar opens and closes, how to maximize your acquisition of free drinks so you don’t even have to go to the bar, and tons more.

And don’t even get me started on my food-related knowledge. I can tell you exactly what refreshments will be served at each event, which lunch line will be the shortest, which cafeteria employee to ask for hot sauce, which pastries are the least stale, and on and on. The buffet-style dinner menu changes daily and follows a theme (Cajun, Italian, etc.), and I have every dinner menu memorized along with a mental ranking of each item’s tastiness, location in the cafeteria, and likelihood of running out (i.e. grab that chocolate cheesecake ASAP).

So yeah, by now I’m a pro. But it wasn’t always so. Here’s a table summarizing how my experience at this meeting has changed over the years:

*PIs = principal investigators, i.e. lab heads

 

Although much has changed over the years, I’ve noticed some experiences that repeat themselves. For example, the roller coaster of emotions associated with the abstract book (some of which I described in my 2015 post). The book comes out about 3 days before the meeting, which leaves plenty of time to get excited, anxious, or panicked about all the science other people are doing.

 

Another trend I’ve noticed is that when you go to a meeting, you meet a lot of new people who tend to ask you the same questions over and over. The most common question is usually “How’s your research going?”, a question that is rarely answered with complete sincerity. Here’s a handy table for formulating and/or interpreting a response to this question:

If you encounter anyone in the latter two categories you may want to buy them a drink.

From genes to neurons

And yes, I’ve also noticed some trends in the actual science that’s presented at this meeting. Since the five meetings I’ve attended have spanned nearly a decade, it’s been interesting to see how the field has changed. I think most people would agree that the most striking trend is the shift toward studying how brain cells (neurons) encode information and contribute to an animal’s behavior, as opposed to studying the genes and molecular mechanisms that operate within those cells.

In addition, the tools for studying specific neurons used to be pretty crappy. If you wanted to activate one specific neuron of interest, you’d probably have to activate 100 other random neurons as well. In just the last few years, the tools for manipulating the activity of specific neurons have gotten WAY better, mostly thanks to the efforts of HHMI’s Janelia Research Campus.

A fly brain (colored purple) where just two of the tens of thousands of neurons have been targeted and labeled in green, using genetic tricks. The goal is to target and manipulate ONLY the neurons you’re studying, and no others—a feat that used to be nearly impossible but is now commonplace. (image from Janelia’s split Gal4 collection)

 

Beyond the availability of better tools, the overall approach to studying the role of neurons in behavior has also shifted. Until very recently, the main strategy for studying the function of specific neurons was to completely shut them down or, conversely, to blast them into firing like crazy, and then see how the fly’s behavior changes. This can still be a valuable approach, but nowadays people seem to realize that it’s a rather blunt instrument: just because silencing or activating a set of neurons makes a fly do something (or not do something), that doesn’t mean you truly understand how those neurons work.

For example, there was a lot more work presented this year that simultaneously analyzed the natural activity patterns of neurons along with the detailed behavior of the fly, a strategy that can provide significant insight into their function. It wasn’t long ago that monitoring the activity of fly neurons in a live animal wasn’t even possible, let alone doing so while the fly engages in an interesting behavior!

There was also a lot of work focused on analyzing behavior itself, in finer and finer detail. We used to define behavior in broad strokes, like saying “the fly feeds on sugar”. Now we break down a single behavior like feeding into many sub-behaviors, such as walking around to localize the sugar, halting locomotion, bending its head downward, extending its proboscis to contact the sugar, pumping the sugar into its mouth, deciding when it’s had enough, retracting its proboscis, bending its head upward, resuming locomotion, and so on. We’ve realized that we need to first understand exactly what an animal is doing in order to understand how those actions are generated by the brain.

Seeing how the field has advanced over the years makes me realize that maybe we’re actually getting somewhere. Understanding the brain, even the tiny brain of a fruit fly, is an enormous, daunting challenge—but one that it seems like we are making real progress toward. I can’t wait to see what the next meeting has in store!

 

PS: If you liked this post, you might like my other posts on attending scientific meetings:

SFN: The Good, the Bad, and the Nerdy

What Happens When You Put 500 Fly Neuroscientists in the Same Place for 5 Days

 


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