constitute the heart of the biological clock in flies, and with some modifications they appear to form a mechanism governing circadian rhythms throughout the animal kingdom, from fish to frogs, mice to humans.

Recently Steve Reppert's group at Harvard and Justin Blau in my laboratory have begun to explore the specific signals connecting the mouse and fruit fly biological clocks to the timing of various behaviors, hormone fluctua tions and other functions. It seems that some output genes are turned on by a direct interaction with the CLOCK protein. PER and TIM block the ability of CLOCK to turn on these genes at the same time as they are producing the oscillations of the central feedback loopsetting up extended patterns of cycling gene activity.

An exciting prospect for the future involves the recovery of an entire system of clock-regulated genes in organ isms such as fruit flies and mice. It is likely that previously uncharacterized gene products with intriguing effects on behavior will be discovered within these networks. Perhaps one of these, or a component of the molecular clock itself, will become a favored target for drugs to relieve jet lag, the side effects of shift work, or sleep disorders and related depressive illnesses. Adjusting to a trip from New York to San Francisco might one day be much easier. S3

The Author

MICHAEL W. YOUNG is a professor and head of the Laboratory of Genetics at the Rockefeller University. He also directs the Rockefeller unit of the National Science Foundation's Science and Technology Center for Biological Timing, a consortium that connects laboratories at Brandeis University, Northwestern University, Rockefeller, the Scripps Research Institute in La Jolla, Calif., and the University of Virginia. After receiving a Ph.D. from the University of Texas in 1975, Young took a postdoctoral fellowship at the Stanford University School of Medicine to study gene and chromosome structure. In 1978 he joined the faculty of Rockefeller, where members of his research group have isolated and deciphered the functions of four of the seven genes that have been linked to the fruit fly biological clock.

Further Information

The Molecular Control of Circadian BeHAvioral Rhythms and Their Entrainment in Drosophila. Michael W. Young in Annual Review of Biochemistry, Vol. 67, pages 135-152; 1998.

Molecular Bases for Circadian Clocks. Jay C. Dunlap in Cell, Vol. 96, No. 2, pages 271-290; January 22, 1999.

Time, Love, Memory: A Great Biologist and His Quest for the Origins of Behavior. J. Weiner. Alfred Knopf, 1999.

A tutorial on biological clocks—including ideas for home and classroom activities—can be found on the National Science Foundation's Science and Technology Center for Biological Timing's site at on the World Wide Web.

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