Peter Gruber Professor of Neuroscience, Brandeis University, Waltham, MA and Investigator, Howard Hughes Medical Institute
The challenge: How does our internal biological clock guide our bodies throughout the day?
The work: Along with Drs. Jeffrey Hall and Michael Young, Rosbash discovered that our circadian clocks are regulated by a small group of genes that work at the level of the individual cell. Subtle mutations in any of these genes can accelerate or slow our daily rhythms.
Why it matters: Their discoveries about the biological clock have applications for sleep and appetite disorders. There are also applications for organs such as the brain, liver, lungs and skin, which use the same genetic mechanisms to control their rhythmic activities
Michael Rosbash, PhD Investigator, Howard Hughes Medical Institute and Professor of Biology, Brandeis University, Waltham, MA
Michael Rosbash was instrumental in revealing the molecular basis of circadian rhythms, the built-in biological clock that regulates sleep and wakefulness, activity and rest, hormone levels, body temperature, and other functions. Using the fruit fly Drosophila, he identified genes and proteins involved in regulating the clock and proposed a theory of how the clock works. Rosbash's discoveries apply to humans and other mammals, and they could ultimately lead to the development of drugs to treat insomnia, jet lag, and other sleep disorders.
After Rosbash came to Brandeis, he became increasingly interested in the influence of genes on behavior. In 1974 he began working with Jeffrey Hall, and in 1984 they cloned the period gene. Several years later, they proposed a mechanism by which a molecular 24-hour clock might work: a transcriptional negative-feedback loop. Their model still holds up, despite discoveries of additional circadian rhythm genes. In essence, the genes that are part of this loop activate the production of key proteins until a critical activity of each accumulates and turns off transcription.
KEY PAPERS related to the discovery.
Reddy P, Zehring WA, Wheeler DA, Pirrotta V, Hadfield C, Hall JC, Rosbash M. Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms. Cell. 28:701-10. 1984
Siwicki KK, Eastman C, Petersen G, Rosbash M, Hall JC. Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system. Neuron 1:141-150. 1988
Allada R, White NE, So WV, Hall JC, Rosbash M. A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell. 93:791-804. 1998