RUI: Intercellular coupling of circadian clock cells in the liver

日常或昼夜节律不仅塑造了我们的日常睡眠-觉醒周期，还塑造了我们的内部生理机能。这些节律是由我们体内许多细胞和组织的生物钟驱动的，并由大脑中的一个起搏器——视交叉上核（SCN）——同步。这个实验室的长期目标是更好地了解体内所有生物钟的重置动态。该项目的目标是确定肝脏内生物钟的特性，特别是肝细胞如何相互沟通以保持一天中一致的时间。这些信息将有助于建立一个更准确的多振荡器昼夜节律系统模型。中心假设是肝脏是一个耦合的昼夜节律振荡器，并且肝细胞在功能上是耦合的，这导致了一些预测，这些预测可以在培养细胞中使用发光测量和生物发光成像进行测试。前三个目标将确定肝脏细胞，肝细胞，传递昼夜周期和相位信息的机制。最终目的是证明肝脏可以在没有SCN输入的情况下保持节律。这些实验将极大地增强对一个功能性的、多层次的昼夜节律系统是如何由数百万个单细胞中的时钟组装而成的理解，以及这个系统在面对频繁的时差反应或轮班工作等干扰时是如何反应的。这些研究将在一所女子本科学院进行，有前途的本科女性，其中许多来自代表性不足的少数群体，将在开展研究中发挥领导作用。参与一个活跃的研究实验室将为有才华的妇女提供鼓励和培训，以便她们开始科学事业。

Daily or circadian rhythms shape both our daily sleep-wake cycles but also our internal physiology. These rhythms are driven by circadian clocks in many cells and tissues within our bodies, and are synchronized by a pacemaker in the brain, the suprachiasmatic nucleus or SCN. This lab has a long-term goal to better understand the resetting dynamics of all the circadian clocks within the body. The objective of this project is to determine the properties of the circadian clock within the liver, and, in particular, how liver cells communicate with each other to keep a consistent time of day. This information will help build a more accurate model of the multi-oscillator circadian system. The central hypothesis is that the liver is a coupled circadian oscillator, and that liver cells are functionally coupled leads to several predictions that can be tested using luminometry and bioluminescence imaging in cultured cells. The first three aims will determine the mechanisms by which the cells of the liver, hepatocytes, communicate information about circadian period and phase. The final aim is to demonstrate that the liver can maintain a rhythm in the absence of input from the SCN. These experiments will greatly enhance the understanding of how a functional, multi-level circadian system is assembled from clocks in millions of single cells, and how this system reacts when confronted with disruptions such as frequent jet lag or rotating shift work. These studies will be conducted at an undergraduate college for women, with promising undergraduate women, many from under-represented minority groups, taking leadership roles in conducting the studies. Participation in an active research lab will provide talented women encouragement and training as they begin scientific careers.