2009 Gruber Neuroscience Prize
The pioneering work of Jeffrey Hall, Michael Rosbash, and Michael Young transformed the field of molecular biology by revealing the gene-driven mechanism that controls circadian (daily) rhythms in the nervous system. Through painstaking research, they established that the circadian rhythms of the fruit fly (Drosophila) are run by a transcriptional negative-feedback loop. They also uncovered many of the interacting genes and gene products that control this mechanism, including a light-sensing protein that uses the day/night light cycle to help synchronize daily behavioral cycles to natural environmental cycles. Subsequent studies by others have demonstrated that these discoveries apply not only to fruit flies, but also to mammals, including humans. Biological rhythms are now understood to play a crucial role in how the human brain—and body—functions.
2009 Neuroscience Prize Recipients
Laureate Profile
When Jeffrey Hall, Michael Rosbash, and Michael Young began their investigations three decades ago into whether genes influenced the behavior of the tiny, humble fruit fly (Drosophila melanogaster), they had no idea where their studies would lead. “When you start on a problem like this, you don’t know how far you will get,” says Young. “Of course, you hope to find out something interesting, but you can’t be sure.”
But something interesting—indeed, groundbreaking—is exactly what they did uncover. Using the then-emerging tools of recombinant DNA, Young (at Rockefeller University) and Hall and Rosbash (at Brandeis University) successfully isolated Drosophila’s period gene, which dictates the day-night activity cycle of the fly. A few years—and much research—later, they proposed the molecular mechanism behind Drosophila’s 24-hour internal clock: a transcriptional negative-feedback loop. Further research from their labs uncovered additional genes and gene products crucial to this mechanism’s timing and operation.
With these discoveries, Hall, Rosbash, and Young clearly established a direct link between genes and behavior. Other scientists have found that these discoveries apply not only to the fruit fly, but to all living organisms, including humans. One of the clinical applications of this research has been the development of chronotherapies, medical treatments that take into account the biological rhythms of the patient and of the disease itself.
All three scientists continue their studies into the molecular workings of Drosophila behavior. Hall, a professor of biology at the University of Maine, is investigating the neurogenetics of the fruit fly’s courtship rhythms. Rosbash, professor and director of the National Center for Behavioral Genomics at Brandeis University, is trying to identify the precise relationship between the pacemaker in the Drosophila circadian clock and the light-dark cycle as well as the neural circuit in the fly’s brain that underlies the circadian rest-activity cycle. Young, professor and head of the Laboratory of Genetics at Rockefeller University, also has several current research foci, including studies of molecular changes in the circadian clock that alter patterns of human sleep.
Citation
The Peter and Patricia Gruber Foundation proudly presents the 2009 Neuroscience Prize to Jeffrey Hall, Michael Rosbash, and Michael Young for their pioneering discoveries of molecular mechanisms that control circadian rhythms in the nervous system.
These investigators established that in the fruit fly Drosophila melanogaster circadian rhythms are driven by a transcriptional feedback loop that controls the expression of the period gene. They discovered a set of interacting genes that control this process, including the light-sensing protein that establishes circadian rhythms in response to the day-night light cycle.
Subsequent work by others demonstrated that these findings apply broadly to both invertebrates and vertebrates and that a mutation in the human counterpart of the period gene causes a human circadian sleep disorder. These discoveries reveal a striking solution to the problem of how genes control a higher-order behavior.
Photo Gallery
