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Mechanisms underlying circadian gating of stress responses

$382,755R35FY2025GMNIH

University Of California Riverside, Riverside CA

Investigators

Abstract

Project Summary To better adapt to their environment and align key metabolic and physiological activities, the circadian clock helps organisms partition specific responses to the most optimal times of the day. In humans, many diseases are characterized by dampened circadian rhythms and symptoms that cluster at specific times of day. In plants, gene expression dynamics in response to environmental stimuli is highly dependent on the time of day, a process referred to as circadian gating. Plants have been an ideal model for investigating circadian gating of stress responses. However, the key regulators involved, the regulatory mechanisms and the functional relevance of circadian gating remain poorly understood. Insights from our research in the model Arabidopsis suggest that the current knowledge of the existing clock proteins is not sufficient to explain the functional mechanisms of gating. Our central hypothesis is that the clock facilitates dynamic protein/DNA interactions, mRNA fate (storage and/or degradation), and dynamic protein complex composition depending on the time of the day to regulate stress tolerance mechanisms. In this proposal, we will continue to leverage the plant model Arabidopsis and a combination of genetics, genomics, biochemical, and molecular biology approaches to identify key regulators involved in gating and investigate how the clock manages stress signals to elicit a response that is then communicated to allow for optimal physiological responses in a changing environment. Plants are an ideal system to engineer or reprogram temporal control of gene expression through manipulating clock-controlled genes. Our long-term goal is to leverage innovative approaches to precisely enhance or engineer time of day specific gene expression responses for positive physiological outcomes. Our research discoveries will bridge the existing knowledge gaps on how signals are partitioned and modulated by eukaryotic clocks and provide new insights that can aid in optimizing protocols for stress resilience, disease treatments, and chronotherapy.

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