The goal of the Vosshall Laboratory is to understand how the brain interprets olfactory signals in the environment that signal food, danger or potential mating partners. Working primarily with Drosophila melanogaster fruit flies, which display a rich repertoire of chemosensory behaviors despite having a nervous system with only 100,000 neurons, Dr. Vosshall’s research has yielded new knowledge about how odor stimuli are processed and perceived.

The long-term goal of the work in the Vosshall lab is to understand how higher olfactory centers process different odor stimuli to yield a conscious percept of a particular smell. The lab uses Drosophila as a model system to study olfaction because of its simplicity and its accessibility to cellular, molecular, genetic and behavioral manipulation and analysis. Employing these methods, Dr. Vosshall’s lab is working to understand how the fly is able to discriminate between the thousands of available odorants in the environment, and how different odors can elicit distinct behavioral responses.

In flies, a large family of novel odorant receptor proteins mediates the first step in olfactory recognition. In Drosophila, this family consists of 62 members, expressed in an intricate and spatially invariant pattern across the 1,500 olfactory neurons that make up the organism’s olfactory sensory organs; because each of these neurons expresses one or a few receptors, each neuron is functionally distinct. Dr. Vosshall’s research has led to a complete map of olfactory projections in developing flies, which allows scientists to relate, for the first time, a large body of work on the electrophysiological response properties of olfactory circuits to the identity of the neurons that connect to it.

Dr. Vosshall’s lab has shown that all neurons expressing a given receptor target one or two spatially invariant areas in the antennal lobe, the site of the first olfactory synapse. These results indicate that the activation of an odorant receptor leads to a unique pattern of synaptic activity, allowing the organism to recognize a smell. One particular member of the odorant gene family, Or83b, is of particular interest to the Vosshall lab, as it highly conserved across insect evolution and is unique in being expressed in nearly all olfactory neurons. Research from Dr. Vosshall’s lab has shown that Or83b functions as a co-receptor that is involved in the transport and maintenance of odorant receptors to the cell surface and may also play a role in ligand recognition or downstream signaling events.

A second set of chemosensory receptors identified by Dr. Vosshall’s lab is responsible for the detection of carbon dioxide and is conserved from flies to mosquitoes. Insects are highly sensitive to carbon dioxide and blood-feeding mosquitoes use this gas to identify vertebrate prey. Dr. Vosshall’s research has pinpointed these proteins, known as Gr21a and Gr63a, as potential targets for inhibitors. Ongoing work in the Vosshall laboratory is studying the Drosophila and Anopheles gambiae (malaria mosquito) carbon dioxide receptor in tissue culture cells. The goal is to identify small molecule chemical inhibitors that interfere with the activity of these proteins. Such compounds could help fight mosquito-transmitted infectious disease.

Experiments in Dr. Vosshall’s lab have also brought to light a fundamental difference in the structure of odorant receptors in the fly compared to mammals. Previously, the molecular basis of all odorant receptors was thought to be a G protein coupled receptor, a class of proteins that help transmit messages across the cell membrane. However, Dr. Vosshall’s research found that fly receptors look nothing like the G protein coupled odorant receptors that mediate smell perception in humans and other vertebrates. Instead, the odor detection mechanism is a striking case of convergent evolution — though flies and humans judge odor intensity in similar ways, they do not use the same mechanisms to perceive odor quality.

To better understand the human olfactory system, the Vosshall lab has initiated psychophysical studies to test whether specific mutations in odorant receptor genes underlie individual differences in odor perception. In a large outpatient study at The Rockefeller University Hospital, she has screened almost 400 normal human volunteers for those unable to smell certain odors. The goal of this work is to relate individual perceptual differences between subjects to polymorphisms in their odorant receptor genes.

CAREER

Dr. Vosshall received her undergraduate degree in biochemistry from Columbia University in 1987, and her Ph.D. from Rockefeller University in 1993. She conducted her postdoctoral training with Richard Axel at Columbia from 1993 to 2000 and returned to Rockefeller as assistant professor in 2000. In 2005, Dr. Vosshall received the New York City Mayor’s Young Investigator Award for Excellence in Science and Technology and the Irma T. Hirschl/Monique Weill-Caulier Trust Research Award. She was named a John Merck Fund Fellow and received the Presidential Early Career Award for Scientists and Engineers in 2002. In 2001, Dr. Vosshall was named a Beckman Foundation Young Investigator and received a McKnight Neuroscience Scholar Award and a National Science Foundation CAREER Award.