9319623 Sehgal All organisms display biological rhythms that are controlled by endogenous clocks. These endogenous oscillators often have a period of about 24 hours, i.e. they are "circadian", and they control important functions such as sleep-wake cycles, maintenance of body temperature, and secretion of hormones. In this proposal Dr. Sehgal will investigate the molecular mechanisms underlying rhythmic behavior. The organism studied will be the fruit fly, where genetic technology has already been used to dissect some components of the circadian clock. One regulator of activity rhythms in the fruit fly is the period (per) gene. When this gene undergoes mutation, the period of circadian rhythms may lengthen, shorten or even be abolished. Dr. Sehgal's group will study a gene called timeless (tim) which appears to operate by influencing the products of the per gene. A combinmation of molecular biological and genetic methods will be used to isolate and characterize tim and to determine how it interacts with per. Recent findings suggest that genes such as per are present in the brains of many animals. Therefore studying per and tim in this system may yield important insights into the molecular architecture of the clock that times all living organisms.***