Just as a pocket watch requires a complex system of gears and springs to keep it ticking precisely, individual cells have a network of proteins and genes that maintain their own internal clock -- a 24-hour rhythm that, in humans, regulates metabolism, cell division, and hormone production, as well as the wake-sleep cycle. Studying this "circadian" rhythm in fruit flies, which have genes that are similar to our own, scientists have constructed a basic model of how the cellular timekeeper works. But now, a new report in this week's issue of the journal Science turns the old model on its head: By providing a glimpse into living cells, Rockefeller University researchers have uncovered a previously undetected clock inside the circadian clock. The scientists made the finding with a rarely used technique called FRET, which enabled them to follow circadian proteins over an extended period of time and watch the clock as it ticks away in a living cell.

At the most basic level, an organism's sleep-wake rhythms are governed by 10 known genes. In the fly, two of those genes -- period and timeless -- produce proteins that fluctuate in a negative feedback loop that takes about 24 hours to complete. At night, two other genes (clock and cycle) stimulate production of Period and Timeless proteins, which begin to accumulate in the cell's cytoplasm. After about six hours, the two proteins move into the nucleus; their presence turns off the genes, which then remain inactive until Period and Timeless degrade and the whole cycle begins anew.

Michael Young, the Richard and Jeanne Fisher Professor at Rockefeller University and head of the Laboratory of Genetics, isolated the first circadian gene, period, in 1984. He and his peers have been piecing together the cellular circadian puzzle ever since, and thought they had some of the basics figured out. Prior studies, which examined the placement of Period and Timeless during different stages of the cycle, seemed to indicate th
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Contact: Joseph Bonner
bonnerj@rockefeller.edu
212-327-8998
Rockefeller University
12-Jan-2006

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