RUI: Intercellular coupling of circadian clock cells in the liver

日常或昼夜节律塑造了我们的日常睡眠-觉醒周期，也塑造了我们的内部生理。 这些节奏是由我们体内许多细胞和组织中的生物钟驱动的，并由大脑中的起搏器（视交叉上核或SCN）同步。 这个实验室有一个长期的目标，以更好地了解体内所有生物钟的重置动力学。该项目的目的是确定肝脏内生物钟的特性，特别是肝细胞如何相互通信以保持一天中一致的时间。这些信息将有助于建立多振荡器昼夜节律系统的更准确模型。核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耦合导致可以使用培养细胞中的发光测定和生物发光成像来测试的几个预测。 前三个目标将确定肝脏细胞（肝细胞）传达昼夜节律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功能性、多层次昼夜节律系统如何由数百万个单细胞中的时钟组装而成的理解，以及当遇到频繁的时差或轮班工作等干扰时，该系统如何反应。这些研究将在一所女子本科学院进行，有前途的女本科生，其中许多来自代表性不足的少数群体，在进行研究中发挥领导作用。参加一个活跃的研究实验室将为有才华的妇女开始科学生涯提供鼓励和培训。

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.