Molecular Biology, Neuroscience
Fred Hutchinson Cancer Research Center
Dr. Buck is also a member of the Basic Sciences Division at Fred Hutchinson Cancer Research Center and an affiliate professor of physiology and biophysics at the University of Washington.
Odor Perception, Neural Circuits, and Behavior
Linda Buck is investigating mechanisms that underlie the sense of smell. Her goal is to understand how the nervous system translates a vast array of environmental chemicals into diverse odor perceptions, hormonal changes, and instinctive behaviors.
Buck’s work has provided key insights into olfaction. She and her colleagues discovered the odorant receptor (OR) family, whose 1,000 members detect odorants in the nose. They found that instead of dedicating an individual OR to a specific odor, the olfactory system uses a combination of receptors to create a specific smell response within the neurons of the brain. This combinatorial approach allows the brain to discriminate between thousands of different odors. Buck’s group also discovered 14 nasal receptors, called TAARs, which have been linked to innate behaviors. Each olfactory sensory neuron in the nose expresses one OR or TAAR gene. Neurons with the same OR are confined to a specific nasal zone, and they send their axons to a few specific glomeruli in the olfactory bulb of the brain. Now Buck is trying to understand how sensory neurons come to express their single receptor gene, and how signals from different receptors are organized in higher brain areas to produce different perceptions and innate behaviors.
Olfactory cues can strongly affect basic drives and hormone levels – such as appetite and sex and stress hormones linked to fear. The Buck team has developed neurotropic viral tracers to map olfactory inputs to subsets of brain neurons involved in these functions. Using a combination of new and established technologies, they are working to uncover receptors in the nose that modulate specific functions and to find molecular identifiers of olfactory and higher- order neurons. Eventually, they’d like to create molecular maps of these complex neural circuits and determine the roles played by the circuits’ neuronal components.
This research was supported in part by grants from the National Institutes of Health and the Department of Defense.
Apple pie baking in the oven, newly mowed grass, sulfur emanating from Fourth of July fireworks—these are just a few of the 10,000 or more distinct odors our noses can detect. Linda Buck studies exactly how odor molecules in the environment are detected by specialized receptors in the nose and then translated by the brain into specific smells. Her groundbreaking research has provided important insights into the mechanisms underlying the sense of smell. And it is for this work that Buck and fellow HHMI investigator Richard Axel won the 2004 Nobel Prize in Physiology or Medicine.
Buck first became interested in odor recognition in the late 1980s, when little was known about how odors are detected or how the nervous system translates various odor molecules into perceived smells. "To me, this was a monumental problem and a wonderful puzzle. I was hooked," Buck recalled.
At that time, olfactory receptors had not yet been discovered. Buck set out to find them. Working as a postdoctoral fellow in Axel's laboratory at Columbia University, she put in 15 hour days for several years before she and Axel found precisely what they were looking for—a family of some 1,000 genes that encode odor receptors located in the lining of the nose.
Buck then used the odor receptor genes as tools to unravel how the identities of different odors are encoded at the molecular level and in the brain to produce the perception of distinct odors. In later studies, she and her colleagues uncovered sensory maps in the olfactory bulb that are virtually identical in different individuals. They also discovered that the sense of smell in mammals relies on a combinatorial approach to recognizing and processing odors. Thus, rather than a specific odor being detected by an individual receptor, the olfactory system uses varying combinations of receptors to produce distinct smells.
Buck continues to be fascinated by the inner workings of the olfactory system, an enthusiasm she hopes to convey to the graduate students and postdoctoral fellows in her lab. "I tell them that it is absolutely essential to work on something that fascinates them and that they are excited about," Buck said.