RUI: Intercellular coupling of circadian clock cells in the liver

Smith College, Northampton MA

Investigators

Abstract

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.