Charles J. Weitz, M.D., Ph.D.
Robert Henry Pfeiffer Professor of Neurobiology
Department. of Neurobiology
Warren Alpert Building, Room 423
210 Longwood Avenue
Boston, MA 02115
We study the molecular biology and genetics of mammalian circadian clocks, intrinsic molecular oscillators that drive daily rhythms in physiology, metabolism, and behavior. The master circadian clocks regulating the sleep-wake cycle and daily rhythms of feeding behavior are located within specific clock cells in the hypothalamus of the brain. In recent years it has become clear that most or all peripheral tissues also contain intrinsic circadian clocks, and emerging evidence indicates that such clocks play important and broad roles in physiology and metabolism, including the regulation of circulating hormones, glucose, and lipids.
A general picture of how circadian clocks are built has emerged in recent years from genetic and biochemical studies. The core mechanism is a transcriptional feedback loop, highly conserved across all animal species, in which the protein products of several dedicated clock genes cooperate to inhibit the transcription factor responsible for their own expression. This feedback loop not only drives self-sustaining oscillations of the clock mechanism itself, but also drives daily rhythms of activation of a large number of genes involved in diverse aspects of cellular, tissue, and systemic physiology. It has become apparent that the clock mechanism is evolutionarily ancient and represents a fundamental biological timing mechanism operating at the level of single cells.
We use molecular biology, biochemistry, and genetics to investigate the mammalian circadian system. The focus of our efforts has been to identify and characterize molecular components of circadian clocks, to identify molecular pathways by which central circadian clocks drive rhythms in behavioral activity, and to determine the physiological functions of clocks in various brain sites and tissues by conditional genetic studies in mice. Recently, we have developed a large-scale proteomics strategy to identify proteins acting in the core circadian clock mechanism, and our initial findings point to unanticipated actions of the core clock proteins in the generation of circadian rhythms.
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Last Update: 11/7/2013