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

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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.