Hall, Rosbash and Young share $500,000 Gruber neuroscience prize

Hall and Rosbash demonstrated, for example, 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. (Transcription is a gene's ability to copy its DNA sequence into messenger RNA, a necessary step for translating the gene into a protein that performs a specialized function in the cell). 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.

As Hall, Rosbash, and Young continued their research, the fundamental workings of this complex feedback system came into even sharper focus. They 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 everyday 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—a tour de force of genetics and molecular biology—has paved the way for the study of human circadian genetics.

"Practically all biological creatures thus display a circadian rhythm, whether fruit fly or man, as some species are active during night and others during daytime. This astounding ability depends on an intricate molecular mechanism that, once developed, has been conserved throughout evolution," says Sten Grillner, Director of the Nobel Institute for Neurophysiology at the Karolinska Institutet. "To reset the biological clock takes many days, as all intercontinental travelers are forced to experience - for shift-workers it is more serious, it creates stress and fatigue that over many years can lead to harmful medical conditions."

Additional Information

The official citation reads: 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.