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

RUI：脑时钟振荡及相关细胞接触和形态的定量分析

• 批准号: 1256105
• 负责人: Rae Silver
• 金额: $ 75万
• 依托单位: Barnard College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1256105&HistoricalAwards=false
• 关键词: RUI; Quantitative; analysis; brain; clock

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.

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/觉醒周期、激素分泌和运动活动。现在可以通过同时测量单个基因、细胞、整个 SCN 组织和行为的时间来确定时钟的工作情况。大约 20,000 个单独的 SCN“时钟”细胞如何在时间和空间上组织起来，作为可靠的时钟来指导整个身体的活动时间，是这项工作的实验重点。这个问题将通过使用新的分子工具、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大量数据的高性能计算机分析来解决：这些工具可以同时监测基因和蛋白质的产生在许多细胞中，在大的组织体积中，在分钟、小时和天的时间尺度上，并将揭示每天的时间在这个系统中是如何编码的。结果将揭示单个神经元的工作如何汇聚以产生昼夜节律脑时钟，并显示大脑如何在面对干扰（例如有缺陷的基因或蛋白质）时进行补偿。女性和少数族裔本科生（通常在计算机科学、数学和统计学领域代表性不足）将直接参与研究的各个方面。他们将获得神经科学研究以及使用计算机进行数据分析和建模的实践经验。 所有开发的教学和科学方法都将公开发布，并在会议、出版物和实验室网站上传播。