The worm may sometimes turn, as the old saying has it, but it can also smell. Neurobiologist Cornelia “Cori” Bargmann discovered that the common roundworm, C. elegans, can smell—and taste—in wider and more subtle ways than anyone had ever suspected. She has built on those discoveries to open a valuable window into the workings of the nervous system and the ways in which genes and environment combine to influence behavior, both in C. elegans and in other more complex animals.
Studying the lowly roundworm sounds like an unlikely method for cutting-edge neuroscience, but it's only one example of Bargmann's creative and original approach to research. She became interested in science at a young age, beginning her undergraduate career at the University of Georgia, where she gained her first laboratory experience making food for fruit flies. After obtaining a degree in biochemistry, she went on to MIT, where she pursued her Ph.D. working with cancer researcher Robert Weinberg. She studied mutations in the Ras gene that lead to bladder cancer and did her thesis work on a rat oncogene, neu, which in a different form was later found to be a key player in human breast cancer.
It was as a post-doctoral researcher with H. Robert Horvitz that Bargmann truly hit her stride. Curious about the molecular biology of the nervous system, she settled upon C. elegans as a model system, even while other researchers busied themselves with mice and fruit flies. But she realized that the relative simplicity of the C. elegans brain (only 302 neurons as opposed to thousands, millions, or billions in higher animals), added to the fact that many of the worm's genes were nonetheless preserved by evolution in more complex organisms, made it an excellent candidate for her plans of studying the relationship between individual neurons and their functions.
Using a technique known as laser ablation, Bargmann painstakingly zapped roundworm neurons one at a time, observing the effects on the worm's food-seeking and chemical-sensing behaviors. She found not only that C. elegans could detect a broad range of chemical signatures with great sensitivity, but that some individual sensory neurons could sense more than one scent. She was able to map the chemosensory system with such accuracy that mutant worms lacking sensitivity to particular chemicals could be identified, which made it possible to study their behavior in great detail
In 1991, Bargmann accepted a faculty position at the University of California, San Francisco, where she continued studying the molecular bases of smell and taste, now working in her own lab. She also expanded her research into other areas, including the embryonic genesis of nerve cells. In 1998, she identified the sax-3 gene involved in axonal development, and in 2003, discovered that a pair of signaling molecules called SYG-1 and SYG-2 act together as a "matchmaker" to connect synapses to each other as the brain develops and grows. This was a major breakthrough in the understanding of the embryonic development of the nervous system, and is also directly relevant to the study of neurological disorders such as epilepsy and stroke, in which synaptic connections are missing or become damaged.
Back in the sightless and soundless world of the roundworm, Bargmann found that its social feeding behaviors, such as a preference for dining alone or with groups of other worms, are controlled by a gene known as npr-1, similar to some human proteins that affect appetite and anxiety. She also noted that environmental factors, including the level of oxygen in the worm's immediate environment, can profoundly affect its feeding behaviors.
In 2004, Bargmann, by then also an investigator for the Howard Hughes Medical Institute, moved to a new position as the Wiesel Professor and head of the Laboratory of Neural Circuits and Behavior at Rockefeller University in New York. The year before, in 2003, she had been elected to the National Academy of Sciences, only one of a numerous list of honors including the Kavli Prize in Neuroscience, the Takasago Prize for olfaction research, and the W. Alden Spencer Award for neuroscience research. Perhaps the most prestigious recognition yet of her scientific accomplishments and stature in her field came in 2013, when she was named as co-chair of the advisory group for President's Obama's Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, intended as the neurological equivalent of the Human Genome Project.
Today, Cornelia Bargmann continues her work with C. elegans, using one of nature's most disregarded and underappreciated critters to achieve fresh insights into the common genetic heritage and behaviors that bind all living organisms together. For a scientist as creative and original as Bargmann, it's only the natural way of doing things.
Information as of April 2015