In vivo characterization of a novel ion channel

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The goal of this research is to characterize the role of a unique ion channel gene, alpha1U (a1U), in circadian rhythms. Although this gene is highly conserved in animals, no functional data existed previously for any a1U ortholog. Drosophila a1U (Dma1U) mutants exhibit inverted activity patterns in light-dark conditions and arrhythmic behavior in constant darkness. The genetic techniques available in Drosophila make this an ideal system in which to study alU function. The GAL4-UAS system and RNA interference will be used to determine the tissue-specific role(s) of Dma1U in circadian rhythms. Immunofluorescence will be used to assess the oscillation of clock components in Dma1U mutants. Given the conservation of circadian components between Drosophila and mammals, these analyses could directly impact future research in mammalian rhythms. Specific Aims: (1) To test the hypothesis that Dma1U regulates the circadian oscillation of clock components in the Drosophila brain. (2) To test the hypothesis that Dma1U functions within the Drosophila pacemaker cells to mediate its effects on circadian rhythms. (3) To test the hypothesis that a1U function within the circadian pacemaker is sufficient to promote rhythmic behavior