Leslie B. Vosshall, Ph.D.
Chemers Family Associate Professor; Investigator, HHMI
Laboratory of Neurogenetics and Behavior
E-mail: leslie@rockefeller.edu
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.
