Regulation of a Pacemaker Neural Output in Drosophila Circadian Rhythms

独立之路奖(K99/R00)的目的是帮助一名新的调查员 建立一个独立的研究项目。在这笔赠款的Roo阶段，调查员将 建立一个独立的实验室，并将解决研究提案的其余目标。这个 研究方案的总体目标是使用模型系统来表征新的dunc79基因 黑腹果蝇。Dunc79充当狭窄的腹部离子通道的正向调节器， 它在昼夜节律的起搏器神经元中起作用，促进节律行为。这项研究将会得到改进 我们对昼夜节律行为的神经和遗传基础的理解。在人类中，存在缺陷的 昼夜节律与严重的疾病有关，如精神健康障碍和新陈代谢 精神错乱。此外，狭窄的腹部离子通道及其调节因子的哺乳动物同源物 Dunc79对健康的其他方面可能也很重要，因为缺乏这两种基因的小鼠很快就会死亡 出生。 这个项目的主要具体目标没有改变原来的提案。Roo阶段的计划是 已注明。(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。 Roo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。ROO为实现这一目标制定的计划包括评估 并绘制了NA和dunc79之间的分子相互作用图谱。(目标3)检验dunc79是 周而复始地管理。计划包括评估dunc79转录本和dunc79转录本的潜在昼夜振荡 蛋白。

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 ROO phase are indicated. (Aim 1) To examine the role of dunc79, a putative NA regulator, in Drosophila circadian rhythms. ROO 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. ROO 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.