Many biological processes cycle rhythmically over a twenty-four hour (circadian) period. Disruptions of this rhythm cause "jet lag" and are a feature of many neurological and psychiatric diseases. In mammals, the pacemaker that controls this rhythmicity lies in a brain structure called the suprachiasmatic nucleus of the hypothalamus. Cells in this nucleus exhibit many cyclic properties, even when removed from the brain and studied in a dish, in vitro. Unfortunately, the isolated cells tend to be unstable and thus are difficult to study for long periods. Dr. Earnest has developed a genetically engineered suprachiasmatic cell that replicates in culture but still demonstrates properties of intact suprachiasmatic cells. With this NSF small grant for exploratory research, he will screen colonies of these cells to determine which ones exhibit the circadian time-keeping function. If the proposed projects demonstrate that circadian timekeeping is a stable functional characteristic of suprachiasmatic clones, potential applications of this experimental model would be limitless and could serve to rapidly advance our knowledge of the cellular and molecular organization of the circadian pacemaker mechanism in the brain. Increased understanding would aid the development of therapies for sleep disorders due to altered time schedules, space flight, and neurological disease.***//
