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人员建立一个独立的研究计划。在这笔赠款的RoO阶段，研究人员将建立一个独立的实验室，并将解决研究提案的其余目标。这项研究提案的总体目标是使用模型系统黑腹果蝇来表征新的dunc79基因。Dunc79作为狭窄的腹部离子通道的正向调节器，在昼夜节律起搏神经元中发挥作用，促进节律行为。这项研究将提高我们对昼夜节律行为的神经和遗传学基础的理解。在人类中，昼夜节律缺陷与严重的疾病有关，如精神健康障碍和代谢障碍。此外，狭窄的腹部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也很重要，因为缺乏这两个基因的小鼠在出生后不久就会死亡。 这个项目的主要具体目标没有改变原来的提案。指出了R00阶段的计划。(目的1)研究Dunc79，一个可能的NA调节因子，在果蝇昼夜节律中的作用。 R00计划包括评估dunc79转录变体对昼夜节律的重要性，以及确定dunc79的缺失是否改变了核心时钟功能或PDF神经肽的表达。 (目的2)研究dunc79对NA的调节机制。R00计划实现这一目标，包括评估和绘制NA和dunc79之间的分子相互作用图。(目的3)检验Dunc79是周期性调控的假说。计划包括评估dunc79转录本和蛋白质的潜在昼夜波动。

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.