The sweet smell of success grew sharply stronger this morning for Richard Axel and Linda Buck when the Nobel Assembly announced that the pair will share the 2004 Nobel Prize in Physiology or Medicine for their pioneering work on the sense of smell.
Their big breakthrough came more than a decade ago, when Buck was a postdoc in Axel's lab at Columbia University in New York City and the pair published the first description of olfactory receptors. These proteins in the back of the nasal cavity bind to odorant molecules that get sucked into the nose. That triggers a biochemical cascade, ultimately generating a nerve impulse that transmits information about smell to the brain. Until that time, very little was known about the molecular basis of smell.
In a landmark 1991 paper in Cell, the pair described a family of about 1000 genes that encode olfactory receptors in mice. The receptor proteins were familiar to researchers--they belonged to a large class of receptor proteins involved in cell signaling--the so-called G-protein coupled receptors. Some previous work had suggested that the long-sought olfactory receptors were in this class, but their sheer number was way beyond what anyone had expected, says Columbia's Stuart Firestein, who was not involved with the research. “We thought 25 or maybe 50 receptors would be really incredible.” (Subsequent research has revealed that humans have fewer working olfactory receptor genes than mice--only about 350.)
The pair's Cell paper paved the way to further advances in understanding how information about smell is organized in the brain. Independently, Axel and Buck, who is now at the Fred Hutchinson Cancer Research Center in Seattle, determined that each olfactory receptor neuron expresses one--and only one--olfactory receptor protein. This provided an essential clue to understanding how the brain distinguishes one smell from another. Any given smell typically activates a handful of the 1000 olfactory receptors, and only activates the subset of olfactory receptor neurons that express those receptors, Axel, Buck, and others found. The particular combination of activated neurons is unique to a particular smell, however. Therefore, by reading out which subset of olfactory neurons are active, the brain can distinguish a good apple from a rotten one, for example.
Although Axel and Buck's work has begun to answer fundamental questions about how the sense of smell functions, it has also raised new questions that have attracted researchers from other fields to study olfaction. Figuring out how an olfactory neuron chooses which of 1000 receptor genes to express, for example, has attracted the attention of geneticists. “They're both magnificent scientists and have made a key discovery that opened a big, big area of research,” says Solomon Snyder, a neuroscientist at Johns Hopkins University in Baltimore.
Related sites
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Buck's site at the Fred
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