Biochemical and Molecular Basis of Circadian Behavior

University Of Memphis, Memphis TN

Investigators

Abstract

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Our internal biological clocks regulate many important aspects of behavior and physiology, from sleep-wake cycle to daily changes in body temperature and blood pressure. Unlike hourglass-type of timers, the oscillator-type of timers such as the circadian clock regulates cyclic processes that will repeat itself upon completion of a cycle. Virtually all cells are circadian oscillators, and understanding how these clocks work inside cells provides the basis for the 24-hr rhythms at the whole animal level. The cellular oscillators are based on an auto-regulatory feedback loop consisting of transcriptional activators and repressors: repressor expression is up regulated by the activators, and ~12 hr later down regulated by the repressors themselves. However, exactly how these proteins function to initiate oscillation and to control the pace of the clock (i.e., period length) remains elusive. In this project molecular and cellular genetic approaches will be used, powered with advanced real-time bioluminescence technology, to elucidate the biochemical and functional properties of these clock proteins that underlie the establishment and maintenance of clock function. Findings from cellular clock models will be validated and further explored in mouse models for biological significance. This project is expected to not only significantly improve our understanding of the biochemical basis of circadian behavior, but also have profound general implications for other disciplines in behavioral neurobiology, helping to decipher how cellular and molecular events connect genes to complex behavior. This project employs multidisciplinary approaches and investigates gene function at multiple levels of circadian organization (cells, tissues/organs, and animals). This research will thus provide unique and integrative training opportunities for graduate and advanced undergraduate students who wish to choose a career in biological sciences and to study gene function at the systems level.