Collaborative Research: Master-Slave Clock Networks: Modeling, Analysis and Neurobiology

结合计算和神经生物学的方法将被用来探索机制，产生内源性的日常（昼夜节律）的哺乳动物的节奏。主昼夜节律起搏点位于下丘脑视交叉上核（SCN）内，由数千个细胞自主振荡器组成。这项工作的一个目标是建立一个大脑切片准备，其中荧光素酶报告允许我们跟踪振荡的关键时钟基因的表达在真实的时间。研究人员将专注于确定基因的转录-翻译反馈回路，这些基因的表达对昼夜节律至关重要。分子方法将被用来选择性地中和特定基因的表达，并检查这种操纵对起搏器和从属振荡器的影响。特别是，主振荡器和它的阻尼奴隶在subparaventricular区之间的关系将被调查;后者包括SCN的主要输出，通过中央时钟调节大部分的生理和行为的其他organis.The智力这项工作的优点是集中在协调的计算建模与神经生物学和分子的方法。它将扩展到分布式振荡器之间的相互作用。这项工作的更广泛的影响包括其应用，以了解与健康有关的条件所产生的时差和轮班工作。此外，这项研究将在阿默斯特的马萨诸塞州大学和全国最大的女子文科学院史密斯学院进行。本科生和研究生将有机会使用最先进的设备进行动手实验，与活跃的研究人员导师一起工作。这种合作努力将为妇女和代表性不足的少数民族提供机会，以获得数学，科学和工程前沿的培训。教学工作将与史密斯学院新成立的皮卡工程计划相结合。定期会议将举行，在学生和教师审查生物钟目前的文献。这项研究的协作和跨学科性质吸引了来自不同背景的学生和教师，包括神经科学，生物学，计算机科学和工程。

A combination of computational and neurobiological methods will be used to explore the mechanisms which generate endogenous daily (circadian) rhythms in a mammal. The master circadian pacemaker, which resides within the suprachiasmatic nucleus of the hypothalamus (SCN), is comprised of thousands of cell-autonomous oscillators. One objective of this work is to establish a brain slice preparation in which a luciferase reporter allows us to track oscillations in the expression of critical clock genes in real time. The researchers will focus on identified transcriptional-translational feedback loops of genes whose expression is critical to circadian rhythmicity. Molecular methods will be used to selectively neutralize the expression of specific genes, and to examine the effects of such manipulations on the pacemaker and subordinate oscillators. In particular, the relationship between the master oscillator and its damping slaves in the subparaventricular zone will be investigated; the later comprises the major output of the SCN through which the central clock regulates much of the physiology and behavior of the rest of the organism.The intellectual merit of this work is centered upon coordination of the computational modeling with neurobiological and molecular approaches. It will extend to interactions among distributed oscillators. The broader impact of this work includes its application to understanding the health-related conditions arising from jet lag and shift work. Furthermore, this research will be carried out both at the University of Massachusetts at Amherst and at Smith College, the nation's largest liberal arts college for women. Undergraduate and graduate students will have opportunities to conduct hands-on experiments using state-of-the art equipment, working with mentors who are active researchers. This collaborative efforts will offer opportunities for women and under-represented minorities to gain training at the cutting edge of mathematics, science and engineering. The instructional efforts will be integrated with the newly formed Picker Engineering Program at Smith College. Regular meetings will be held, at which students and faculty review the current literature on biological clocks. The collaborative and interdisciplinary nature of this research draws together students and faculty from diverse backgrounds including Neuroscience, Biology, Computer Science, and Engineering.