RUI: Quantitative analysis of brain clock oscillations and associated cellular contacts and morphologies

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The suprachiasmatic nucleus (SCN) of the mammalian brain is a master daily clock, controlling the timing of virtually all bodily functions, including sleep/wake cycles, hormonal secretions and locomotor activity. It is now possible to determine how well the clock is working, by simultaneously measuring timing in individual genes, cells, whole SCN tissue and behavior. How the ~20,000 individual SCN "clock" cells are organized in time and space to serve as a reliable clock that directs the timing of activities throughout the body is the experimental focus of the work. This problem will be addressed using new molecular tools, animals with mutations in clock genes, bioluminescent cells that continuously signal the expression of clock genes, along with high powered computer analyses of tremendous amounts of data: These tools enable simultaneous monitoring of gene and protein production in many cells, in large tissue volumes, and over time scales of minutes, hours and days, and will reveal how daily time is coded in this system. The results will reveal how the workings of individual neurons converge to produce a circadian brain clock, and to show how the brain compensates in the face of disruptions (such as defective genes or proteins). Women and minority undergraduates (generally underrepresented in computer sciences, mathematics, and statistics) will be directly involved in all aspects of the research. They will get hands-on experience in neuroscientific studies and in using computers for data analysis and modeling. All teaching and scientific methods developed will be made publicly available and contributions disseminated in meetings, publications and on the lab web site.