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.
Defective circadian rhythms in humans are associated with serious conditions such as mental health disorders and metabolic disorders. The fruit fly Drosophila is a proven model system for characterizing genes that regulate circadian rhythms, and many of these genes have similar functions in mammals, including humans.
|Flourakis, Matthieu; Kula-Eversole, Elzbieta; Hutchison, Alan L et al. (2015) A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability. Cell 162:836-48|
|Lear, Bridget C; Darrah, Eric J; Aldrich, Benjamin T et al. (2013) UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila. PLoS One 8:e78147|