Music to the ears of neuroscientists worldwide, the White House recently announced its intention to launch a multibillion-dollar decade-long science initiative to map the human brain, a project equal in scope and significance to the Human Genome Project. The goal is to move toward a fundamental understanding of how the brain works by fully elucidating the microcircuitry of the brain.
The groundwork for this ambitious program is already being laid at research centers around the world, where scientists are investigating the nervous systems of various model organisms, such as the nematode C. elegans and the fruit fly Drosophila melanogaster, and inventing new instrumentation to study neuronal activities. At Janelia Farm, the Howard Hughes Medical Institute’s pioneering research center in Virginia, Vassar alumnus Wyatt Korff ’96, leads the Fly Olympiad, a team of scientists investigating how neurons in the brain of the fruit fly govern behavior.
Why fruit flies? “For one thing, flies have a smaller number of neurons—around 100,000 in the adult fruit fly as opposed to about 100 billion in the human brain,” Korff says. “And the fly brain is more stable. There’s less context-dependent remodeling of neurons in the fly brain, so if you’re looking at a fly from a particular line today, and another fly from the same line a month from now, they’re going to behave very similarly.”
There are two basic approaches to brain mapping, and both are going on simultaneously at Janelia and elsewhere. One is to create a “connectome,” a comprehensive structural description of the network of neurons and synapses that comprise the central nervous system. The other is to create a functional map by figuring out which neurons do what. That’s what the Fly Olympiad aims to do.
Korff’s team devised a series of behavioral experiments to screen thousands of Drosophila lines, with a focus on locomotion, vision, aggression, reproduction, social interactions, and other behaviors. “Using genetic tools that were created by Gerald Rubin, the executive director here at Janelia, we target subsets of neurons in the fly brain, either silencing or hyperactivating a targeted population of neurons, and then we assay the behavioral consequences of manipulating those neurons.”
“For example, most flies move toward light,” Korff says. “In fact, most insects move toward light, which you can see if there’s a light on outside your house on a summer night. We’ve identified neurons that are associated with a repulsive stimulus, and when we manipulate those neurons, we can invert the behavior so that the flies move away from the light source.”
Korff’s team completed the initial screen in August 2012, and they’re now analyzing the data. In the coming year, they expect to publish the results and also to make available to the scientific community the plans for the behavioral gizmos developed by the Olympiad as well as the software to run them.
Korff says that his decision to pursue a career in science was largely due to the influence of Vassar biology professor John Long. Sophomore year, he took Long’s class on Animal Structure and Diversity. “Not only were John’s lectures amazing and captivating and his explanations incredibly clear and the subject matter very interesting, but the labs he put together were very hands-on. We learned how the tail fin mechanism of a crayfish works by building a physical model. It was just awesome.”
Korff has pretty much always been interested in mechanics. He opened a bike shop in his garage in Tucson, Arizona, when he was a teenager and ran the bike shop in the basement of Strong House while he was at Vassar. So, Long’s approach to biology—building gadgets to explore biological and evolutionary questions—roped Korff into the fold. He was one of Long’s Undergraduate Research Summer Institute (URSI) fellows the summer after his junior year and had the opportunity to present his work at several national conferences. “It was pretty amazing because here we were, undergrads, and John was not only allowing us but really pushing us to present our work at these scientific conferences and teaching us how to give effective talks. That kind of mentorship and training is something even people in graduate school don’t often get.”
Korff took a year off after Vassar to race bikes before heading off to graduate school at Berkeley, where his Ph.D. research focused on the biomechanics of lizards running on sand. He then took a postdoc at Caltech, with Michael Dickinson, where he switched his research focus to the nervous system of Drosophila—all the while continuing to nurture his interest in gizmology.
“When I was deciding what I wanted to do next, I was looking for an alternative to the all-consuming career that seems to be the model at traditional academic research institutions,” Korff says. “My wife and I had just had our first child, and I wanted to find a work-life balance that would give me the amount of quality time I wanted with my family.”
He had a job offer in Silicon Valley, but then the Fly Olympiad position opened up at Janelia. “This is actually the perfect hybrid for me. The institute is focused on these really lofty questions about how the brain is organized, but we’re also developing novel instrumentation for visualizing that. So, we’re really at the cutting edge. I’d say that there are only a few places in the world of this scientific caliber, and to be able to work in this environment and contribute to these scientific outcomes—and, at the same time, have a more balanced life—is awesome.”
Meanwhile, the John Long legacy continues to unfold. Janelia is always looking for talented scientists interested in neuroscience, so when Korff was recruiting team members for the Olympiad, he contacted Long, who sent him two recent Vassar grads—Sonia Roberts ’10 and Jonathan Hirokawa ’10. “They were both here at Janelia for about two years,” Korff says, “and I’m happy to say that they’ve both moved on to graduate school.” Hirokawa is pursuing a master’s in engineering at Boston University, and Roberts is pursuing her Ph.D. at the University of Pennsylvania and building bio-inspired robots.