Regulation of a Pacemaker Neural Output in Drosophila Circadian Rhythms

独立之路奖（K99/R00）的目的是帮助新的研究者建立一个独立的研究项目。在该资助的ROO阶段，研究者将建立一个独立的实验室，并将解决研究计划的剩余目标。该研究计划的总体目标是利用果蝇模型系统表征新的dunc79基因。dunc79作为窄腹离子通道的正调节因子，在昼夜节律起搏器神经元中起作用，促进节律性行为。这项研究将提高我们对昼夜节律行为的神经和遗传基础的理解。在人类中，昼夜节律缺陷与精神健康障碍和代谢紊乱等严重疾病有关。此外，窄腹离子通道及其调节因子DUNC79的哺乳动物同源物可能对健康的其他方面很重要，因为缺乏任何一种基因的小鼠在出生后不久就会死亡。

The aim of the Pathway to Independence Award (K99/R00) is to assist a new investigator in the establishment of an independent research program. In the ROO phase of this grant, the investigator will establish an independent laboratory and will address the remaining aims of the research proposal. The overall goal of the research proposal is to characterize the novel dunc79 gene using the model system Drosophila melanogaster. dunc79 acts as a positive regulator of the NARROW ABDOMEN ion channel, which functions in circadian pacemaker neurons to promote rhythmic behavior. This research will improve our understanding of the neural and genetic basis of circadian rhythmic behaviors. In humans, defects in circadian rhythms are associated with serious conditions such as mental health disorders and metabolic disorders. Moreover, mammalian homologs of the NARROW ABDOMEN ion channel and its regulator DUNC79 are likely to be important for other aspects of health, as mice lacking either gene die shortly after birth. The main specific aims of this project are unmodified from the original proposal. Plans for the R00 phase are indicated. (Aim 1) To examine the role of dunc79, a putative NA regulator, in Drosophila circadian rhythms. R00 plans include assessing the importance of dunc79 transcript variants to circadian rhythms, and determining whether the loss of dunc79 alters core clock function or expression of the PDF neuropeptide. (Aim 2) To examine the mechanisms of dunc79 regulation of NA. R00 plans for this aim include assessing and mapping molecular interactions between na and dunc79 . (Aim 3) To test the hypothesis that dunc79 is circadianly regulated. Plans include assessing potential circadian oscillations of dunc79 transcript and protein.