Despite its microscopic size, the humble worm known as C. elegans may hold clues to an age-old question: Which aspects of an individual's behavior are determined by genes, and which are influenced by experience?
In this transparent, 1-millimeter-long worm that is both deaf and blind, Cornelia Bargmann investigates how the wiring of the brain is organized and influences behavior. "The brain is the source of our behaviors, thoughts, perceptions, emotions, and memories; it is what makes us human," Bargmann explained. "As a biological organ, the brain is constructed by genes. We want to understand what the important genes are."
The keen sense of smell in C. elegans has provided a unique opportunity for Bargmann to understand the interface between genetics and experience. On the one hand, many responses to odors are genetically determined, like the favorable response by human infants to the smell of vanilla. On the other hand, a bad experience, like getting sick after eating a particular food, can create a lifetime aversion to its smell.
While the human brain has billions of neurons, the C. elegans brain has only 302, of which 32 are dedicated to smell, making it an ideal model for studying the relationship among genes, neural circuits, and behavior. Yet, the brains of worms and humans share many of the same features of wiring and function, and many of the genes found in C. elegans are also in humans. "When we understand the worm's brain, we'll be in a much better position to understand the complex functions of the human brain," Bargmann noted.
In 2003, her lab discovered a "matchmaker" signaling molecule, known as SYG-1, which directs neurons to form connections with each other during early development. The finding was a major advance in scientists' understanding of the formation of nerve fibers and is relevant to brain diseases such as epilepsy, where the correct nerve cell connections either do not form at all or form abnormally.
In other studies, Bargmann's lab pinpointed a gene called npr-1 that determines whether worms prefer to eat alone or in social groups and is closely related to a human protein involved in regulating appetite and anxiety. And by studying mutant worms that can detect odors but can't tell them apart, she discovered a gene responsible for odor discrimination and determined how worms can recognize and distinguish among thousands of odors in their environment.
Despite Bargmann's many successes, her career had a modest beginning. As a college student, she made fly food in the laboratory of Wyatt Anderson, a population geneticist at the University of Georgia, as a way to keep busy during the summer months. "But Wyatt decided that I needed to do research, and assuming that I was more of a 'molecular' type, he marched me into Sidney Kushner's office (a geneticist), and informed us both that I'd be working there," Bargmann recalled.
It was the start of a fulfilling and exciting career, one in which Bargmann has worked with first-rate scientists, including her thesis advisor Bob Weinberg and her postdoctoral advisor Bob Horvitz, who won the Nobel Prize in Medicine or Physiology in 2002. "If I have one piece of advice for scientists, it would be to surround yourself with the most exciting and brilliant people you can find," Bargmann suggested. "I secretly think this is the one thing that has contributed most to my success."