Regulation of a Pacemaker Neural Output in Drosophila Circadian Rhythms

Pathway to Independence Award（K99/R 00）的目的是帮助新的研究人员建立独立的研究计划。在该资助的ROO阶段，研究者将建立一个独立的实验室，并将解决研究提案的其余目标。该研究计划的总体目标是使用模型系统果蝇来表征新的dunc 79基因。dunc 79作为NARROW ABDOMEN离子通道的正调节剂，其在昼夜节律起搏神经元中起作用以促进节律行为。这项研究将提高我们对昼夜节律行为的神经和遗传基础的理解。在人类中，昼夜节律的缺陷与严重的疾病有关，如精神健康障碍和代谢紊乱。此外，NARROW ABDOMEN离子通道及其调节因子DUNC 79的哺乳动物同源物可能对健康的其他方面很重要，因为缺乏这两种基因的小鼠在出生后不久就会死亡。 该项目的主要具体目标与最初的提案没有任何变化。R 00阶段的计划已被指明。(Aim 1）研究dunc 79在果蝇昼夜节律中的作用。 R 00计划包括评估dunc 79转录变体对昼夜节律的重要性，并确定dunc 79的丢失是否改变了核心时钟功能或PDF神经肽的表达。 (Aim 2）探讨dunc 79对NA的调控机制。r 00计划包括评估和绘制na和dunc 79之间的分子相互作用。(Aim 3）验证dunc 79受昼夜节律调控的假说。计划包括评估dunc 79转录本和蛋白质的潜在昼夜振荡。

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.