VOLUME 12, NUMBER 16 • FEBRUARY 23, 2001

An Alumna Sets Up Lab

Rockefeller alumna Leslie Vosshall is head of the Laboratory of Neurogenetics and Behavior.

When Rockefeller alumna Leslie Vosshall came back to campus in October, she wasn’t just going to be working in a lab but running it. Vosshall, head of the university’s new Laboratory of Neurogenetics and Behavior, is trying to understand the molecular basis of olfaction (the sense of smell) in the fruit fly. Scientists know a lot about fruit fly behavior, but little is known about how the flies recognize food sources.

As a graduate student, Vosshall worked in Michael Young’s Laboratory of Genetics. "Mike Young made enormous strides in understanding how genes impact behavior," says Vosshall. "In the last 15 years, he’s identified many of the important molecular components that regulate the circadian clock. Remarkably, these same components are now also showing up in the analysis of the vertebrate clock." What she wants to do is apply the same sort of analysis to olfactory behavior.

The sense of smell is very distinct from other sensory systems. Olfactory systems are designed to detect stimulus quality and concentration in the environment, a complex task considering that there are thousands of different odors. Olfactory systems also appear not to be evolutionarily related. "There's a dividing line at vertebrates," she said. Nematodes and flies, for example, use different gene families for olfaction. "The proteins have a similar structure but the amino acid sequences are completely different. Nature found many ways to solve the same problem."

The fruit fly Drosophila has very specific olfactory behavior strategies. Like other insects, it is a specialist and has narrow food interests. The fly has a repertoire of 61 odorant receptors, which are distributed among different olfactory neurons in the antenna. "That’s probably how you get specificity," she says. Fruit flies love ethyl acetate, for example. Vosshall is looking to associate particular receptors with their corresponding odorants, and to understand how functional olfactory wiring patterns are established in development.

One of Vosshall’s goals is to understand why some odorants lead to attraction and some to repulsion. She is also interested in how odorants interact with olfactory neurons and how this interaction is encoded in the brain to lead to stereotyped behaviors.

"A classic question in neurobiology is whether synaptic activity is required for the development of functional synapses or whether animals are genetically wired," says Vosshall. Using what she calls "genetic trickery," her lab is silencing neurons and allowing the flies to develop, then reactivating the neurons. This allows the researchers to see whether a functional olfactory system can form in the absence of activity.

Behavior is hard to study, she says, because it involves the interaction of complex neural circuits. Her lab is now conducting studies with larvae ("They live to eat") to try to determine the range of odorants they respond to. The researchers hope to be able to identify reproducible larval behaviors that can be the basis of further genetic studies.

The fruit fly is an appealing study subject because it is relatively simple, has robust olfactory behaviors, and can be genetically manipulated. She notes that Assistant Professor Peter Mombaerts, head of the Laboratory of Developmental Biology and Neurogenetics, is looking at some of the same questions in mice. "Hopefully there can be some cross-pollination," she says.

Vosshall is glad to be back on campus. "One great change," she says, "is a real commitment to junior faculty. President Levine is actively recruiting and expanding."

Vosshall also appreciates how helpful the university’s administration was in helping her set up her first lab. "The Rockefeller infrastructure is a well-oiled machine," she says. Starting a new lab involves dealing with Purchasing, Maintenance, Sponsored Programs and other offices. "Everyone was incredibly helpful," she says. "At other places, I think it can sometimes be more of a struggle. Rockefeller is a real paradise for junior faculty.