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

> **NIH NIH F32** · DARTMOUTH COLLEGE · 2021 · $68,562

## Abstract

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 period 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. Much of the current knowledge on circadian
biology has come from Neurospora, as its core clock network is functionally homologous to the mammalian
clock. Casein kinase activity is required for normal TC in both fungal and animal cells, but additional regulators
of TC and the specific targets for phosphorylation by CKs have not been systematically investigated. The
clock’s period is also compensated to different concentrations of glucose, which involves transcriptional
repressor machinery in Neurospora. It is currently unknown if TC and NC regulatory pathways are distinct, or if
the core clock is modified similarly in the presence of fluctuations in environmental conditions. I propose to 1)
systematically screen for mutants with defects in TC and NC by leveraging the knockout collection of the
Neurospora model system; 2) identify Casein Kinase 2 targets during TC using a chemical genetics and mass
spectrometry approach; and 3) model interactions between the core clock network and compensation effectors
to determine if computational perturbations match experimental data on circadian period length. The goal of
this work is to characterize compensation, a defining feature of eukaryotic circadian clocks. Humans with sleep
disorders or shift work exposure, or who continually experience jet-lag, have a higher risk to develop cancer,
cardiovascular disease, or metabolic syndrome due to chronic dyssynchrony between their cell-based
molecular clocks cycling and environmental light:dark cycles. Thus, an improved mechanistic understanding of
how the clock is buffered against environmental changes will have diagnostic and therapeutic utility.

## Key facts

- **NIH application ID:** 10058845
- **Project number:** 5F32GM128252-03
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Christina Kelliher
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2018-11-22 → 2022-02-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058845

## Citation

> US National Institutes of Health, RePORTER application 10058845, Genetic and Molecular Dissection of Regulatory Mechanisms Underlying Temperature and Nutritional Compensation of the Circadian Clock in Neurospora crassa (5F32GM128252-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058845. Licensed CC0.

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