Genetic and Molecular Dissection of Regulatory Mechanisms Underlying Temperature and Nutritional Compensation of the Circadian Clock in Neurospora crassa

项目概要/摘要： 生物钟具有计时功能，可以预测环境中的每日变化， 地球上几乎所有的真核生物。~24小时的昼夜节律周期长度对波动有缓冲作用 在外部条件下，包括温度和营养水平，在一个普遍存在的现象， 赔偿在任何真核生物中， 有机体该项目的长期目标是了解温度补偿（TC），营养 补偿（NC），以及补偿效应器和核心时钟之间的分子相互作用 网络使用的模式真核生物粗糙脉孢菌。尽管研究和培训工作在很大程度上 受COVID-19大流行的干扰，对TC和NC缺陷突变体的反向遗传筛选被 使用脉孢菌敲除收集完成（Aim 1）。具有NC缺陷的突变体的数量 由于这项工作，增加了一倍以上。鉴定TC相关的质谱实验 酪蛋白激酶1和2的底物的研究进展顺利，预计将于2022年发表（目标2）。 该行政补充将支持额外几个月的专业发展培训， 2019冠状病毒病大流行以及在NRSA奖学金下发表第三篇第一作者手稿。 由于研究的完成，昼夜节律补偿的分子机制开始形成 在这个项目下。这项研究和未来的独立研究项目将解决24小时昼夜节律是如何改变的问题。 研究发现，在不同的营养水平和环境温度下， 这对患有昼夜睡眠障碍、轮班工作者、持续时差反应和其他疾病的人有影响。 时间生物学条件

Project Summary/Abstract: The circadian clock serves a time-keeping function to anticipate daily changes in the environment and is used by almost every eukaryote on the planet. The ~24-hour circadian period length is buffered against fluctuations in external conditions, including temperature and nutrient levels, in a ubiquitous phenomenon called compensation. The molecular mechanism underlying compensation is not well understood in any eukaryotic organism. The long-term goal of this project is to understand temperature compensation (TC), nutritional compensation (NC), and the molecular interactions between compensation effectors and the core clock network using the model eukaryote Neurospora crassa. Although research and training were significantly disrupted by the COVID-19 pandemic, the reverse genetic screen for mutants with defects in TC and NC was completed using the Neurospora knockout collection (Aim 1). The number of mutants with NC defects has more than doubled because of this work. The mass spectrometry experiments to identify TC-relevant substrates of Casein Kinase 1 and 2 are well underway, and publication is anticipated in 2022 (Aim 2). This Administrative Supplement will support additional months of professional development training lost to the COVID-19 pandemic as well as publication of a third first-author manuscript under this NRSA fellowship. Molecular mechanisms of circadian compensation are beginning to take shape due to research completed under this project. This and future independent investigator projects will resolve how the ~24-hour circadian period length is maintained in the face of different nutrient levels and temperatures in the environment, findings that have implications for humans with circadian sleep disorders, shift workers, continuous jet-lag, and other chronobiological conditions.