Temperature entrainment of the molecular circadian clock circuits in Drosophila.

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Many organisms rely on internal circadian clocks to organize their biological functions in an optimal daily schedule. Disruption of circadian clock function has been associated with negative outcomes for health and well-being, for example, in relation to sleep disorders, diabetes, high blood pressure, and cancer. Circadian clocks have a paradoxical relationship with temperature. On one hand, they employ so-called temperature compensation mechanisms to reliably keep daily time over a range of temperatures, but on the other hand they synchronize to daily temperature cycles with remarkable sensitivity. Daily rhythms in body temperature, which are themselves controlled by a clock in the brain, are thought to play a major role in maintaining synchrony between the clocks in different tissues. The fruit fly Drosophila melanogaster is an excellent model system for studying the internal circadian clocks that animals and humans use for daily time keeping. While little is known about the mechanisms that allow circadian clocks to maintain these sophisticated temperature responses, the Drosophila period (per) gene and its mammalian counterparts are thought to play a key role in daily time keeping as well as temperature entrainment and temperature compensation. The proposed project focusses on the impact of the recently discovered temperature-driven induction of the Drosophila per gene on temperature synchronization and compensation of daily time keeping. The sequence elements and transcription factors involved in this process will be identified by genetically testing different segments of the per gene as well as different potential regulators, respectively. Next, the functional importance of this process will be defined by describing changes in molecular or behavioural circadian rhythms resulting from genetic disruption of the required regulatory sequences and transcription complexes. Given the high degree of structural and functional similarity between the per genes of flies and mammals, discoveries made for the role of temperature-driven per expression in the regulation of behavioural and molecular rhythms in flies are also relevant to understanding the impact of per expression in humans and other mammals on circadian physiology.