The 2009 Neuroscience Prize of The Peter and Patricia Gruber Foundation is being awarded to three scientists for their discoveries of the molecular mechanisms that control circadian rhythms in the nervous system. The foundation honors contemporary individuals in specific fields whose groundbreaking work provides new models that inspire and enable fundamental shifts in knowledge and culture.
The research of Jeffrey Hall, PhD, professor of neurogenetics at the University of Maine, Michael Rosbash, PhD, professor and director of the National Center for Behavioral Genomics at Brandeis University, and Michael Young, PhD, professor and head of the Laboratory of Genetics at Rockefeller University, was the first to establish a simple relationship between single genes and a complex behavior.
In 1984 Hall and Rosbash, working at Brandeis University, and Young, working at Rockefeller University, simultaneously cloned the period (per) gene of the fruit fly, Drosophila melanogaster. This discovery led to subsequent studies from all three labs that eventually unmasked the general molecular mechanism for circadian clocks: a transcriptional feedback loop that oscillates during the 24-hour cycle.
Hall and Rosbash demonstrated that per gene products exhibit oscillations for their concentrations and that during a daily cycle the per protein represses transcription of the very gene that specifies that “final” product.
Young identified per’s partner gene, timeless (tim), and then showed that when these two genes’ protein products (PER and TIM) reach certain levels, they bind together in the cell’s cytoplasm and are transported back into the nucleus, where primarily PER shuts down the genes that made them. After a few hours, the proteins degrade, the genes start up again, and the cycle begins anew.
Hall, Rosbash, and Young discovered other genes and protein products that play critical roles in regulating the loop. They found that mutations affecting any of these genes had effects on Drosophila’s molecular rhythms—and on its behavior. They also identified how certain stimuli, most notably the light-dark cycle, help regulate the feedback loop in order to reset the clock every day to operate in synch with natural environmental cycles (a key and universal feature of daily rhythms).
When other researchers investigated the clock mechanisms in mammals, they found them to be strongly analogous to what Hall, Rosbash, and Young had found in Drosophila. Thus, the uncovering of the mechanism in the fruit fly has paved the way for the study of human circadian genetics.
The scientists will receive the award on October 18 at the annual meeting of the Society for Neuroscience in Chicago.
