Many organisms have daily rhythms of gene expression and behavior, which are controlled by circadian pacemakers. Endogenous circadian periods differ from the precise 24hr rotation of the earth. Nonetheless, circadian clocks keep accurate 24hr time under normal conditions, as they are reset every day by the precise 24hr environmental cycling of signals like light and temperature. Entrainment by temperature is less well-understood than light entrainment, but it is known that clocks of many species including mammals can be entrained by a regular temperature cycle that oscillates by only a degree or two. Moreover, Drosophila circadian rhythms can be reset by temperature pulses, a phenomenon that resembles light pulse-mediated phase shifts. We have recently shown that the photoreceptor cryptochrome is not only critical for light-mediated phase shifts but also for heat-mediated phase shifts. It is also essential for the loss of temperature compensation that takes place in the pe/strain. Temperature compensation is a universal but poorly understood feature of circadian clocks and is intimately tied to the fundamental timekeeping process, which is largely conserved between Drosophila and humans. I proposeto investigate the problem of temperature compensation in Drosophila as well as to explore further the relationship of CRY to heat-mediated phase-shifting and entrainment. In addition, temperature almost certainly has CRY-independent routes through which it can influence circadian rhythms, and we will try to identify other molecules important for temperature entrainment. This search will be aided by experiments with Drosophila mojavensis, which is the most thermotolerant Drosophila species characterized. Lastly, we will attempt to verify the reports of circadian rhythms in C. elegans. We will assay locomotor behavior as well as use microarrays to search for temperature-entrained transcripts. This strategy should identify central clock molecules as well as those processes under clock control in this species. Circadian rhythms are central to many aspects of human physiology and health, including metabolism and the sleep-wake cycle. Understanding the basic principles and molecules that underlie animal clocks is therefore central to the development of more effective therapeutics affecting sleep and vigilance.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Brandeis University
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