Endogenous molecular clocks synchronize organisms' behavior and physiology with the daily day-night cycles they experience. Such common human conditions as sleeping disorders and jet lag are caused by molecular clocks which are desynchronized from their environments. Drosophila flies have a small number of pacemaker neurons in their brain which control rhythmic behavior. The functions of about a dozen genes which compose the molecular clock in these neurons are currently well characterized. How oscillations in clock gene expression are translated into output signals that regulate the timing of Drosophila behavior is largely unknown. Characterizing the output of the Drosophila pacemaker neurons is the subject of this proposal. Pacemaker neurons in mutant backgrounds which """"""""freeze"""""""" the molecular clock at different phases will be isolated, and genomic analysis will be performed, with the goal of identifying differently regulated genes which are candidate clock output factors. Mutations in a subset of these genes will be analyzed behaviorally to test which, if any, rhythmic behavioral outputs they disrupt. Then, some of these genes will be studied molecularly to determine how they are regulated by the central clock.
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