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

哺乳动物大脑的视交叉上核(SCN)是一个主时钟，控制着几乎所有身体功能的时间，包括睡眠/清醒周期、激素分泌和运动活动。现在，通过同时测量单个基因、细胞、整个SCN组织和行为的时间，可以确定时钟工作得有多好。如何在时间和空间上组织大约20,000个单独的SCN“时钟”细胞，作为一个可靠的时钟来指导全身活动的时间安排，是这项工作的实验重点。这个问题将使用新的分子工具、具有时钟基因突变的动物、持续发出时钟基因表达信号的生物发光细胞，以及对海量数据的高性能计算机分析来解决：这些工具能够同时监测许多细胞、大组织体积和几分钟、几小时和几天的时间尺度上的基因和蛋白质生产，并将揭示每天的时间是如何在这个系统中编码的。这些结果将揭示单个神经元的工作如何汇聚，产生一个生物钟，并展示大脑如何在面对干扰(如缺陷基因或蛋白质)时进行补偿。女性和少数族裔本科生(通常在计算机科学、数学和统计学专业任职人数较少)将直接参与研究的各个方面。他们将在神经科学研究以及使用计算机进行数据分析和建模方面获得实践经验。所有制定的教学和科学方法都将公之于众，并在会议、出版物和实验室网站上传播贡献。

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.