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.

哺乳动物大脑的上核（SCN）是每日主时钟，它控制了几乎所有身体功能的时机，包括睡眠/唤醒周期，荷尔蒙分泌和运动活性。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状况。如何在时间和空间中组织约20,000个单独的SCN“时钟”细胞，以作为指导整个体内活动时间安排的可靠时钟。将使用新的分子工具，具有时钟基因突变的动物，不断信号的钟基因表达的动物以及大量数据的高功率分析：这些工具可以同时监测基因和蛋白质的大量细胞，在大量的组织中，每天的时间和时间都将在时间，时间和时间上，这些工具可以同时同时监测基因和蛋白质。结果将揭示单个神经元的起作用如何收敛以产生昼夜节律的大脑时钟，并显示面对破坏（例如缺陷基因或蛋白质）的大脑如何补偿。妇女和少数族裔本科生（通常在计算机科学，数学和统计中代表性不足）将直接参与研究的各个方面。他们将获得神经科学研究和使用计算机进行数据分析和建模的动手经验。 开发的所有教学和科学方法都将公开可用，并在会议，出版物和实验室网站上进行贡献。