# Temperature and metabolic compensation mechanisms in a circadian clock system

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, MERCED · 2023 · $73,810

## Abstract

Project Summary/Abstract
Circadian clocks are intracellular enzymatic systems that provide a reliable biochemical
representation of local time with profound consequences to health across diverse
organisms. Unlike most enzymes, biological clocks are insensitive to a range of
physiological temperatures and cellular energy levels so that organisms can anticipate
dawn and dusk reliably. Another criterion of circadian clocks is that they can be
entrained through environmental cues and thereby stay synchronized to local time.
However, the mechanisms of these defining hallmarks remain incompletely resolved in
any organism, and thus represent outstanding gaps in knowledge across the field of
biological timekeeping. Therefore, the overall vision for the next five years is to build
upon our prior work to elucidate the mechanisms of temperature and metabolic
compensation and entrainment in the circadian clock of cyanobacteria, a system widely
valued by the circadian clocks community. Because proteins and their interactions
underpin clock mechanisms regardless of organism, lessons learned here are expected
to serve as important points of reference for the scientific community working on diverse
circadian clocks. Over the past 20 years, we have made many impactful discoveries on
mechanism of the cyanobacterial clock and developed innovative methodologies and
tools along the way. Our lab recently reconstituted the intact cyanobacterial clock in vitro
such that each component can be monitored in real time over several days, and our
refined and predictive model is the framework for our hypotheses regarding
mechanisms of temperature compensation, metabolic compensation, and entrainment.
Thus, we are very well positioned to succeed at filling these critical gaps in knowledge.
A major expected outcome of the work proposed here is a detailed cause-and-effect
model linking clock protein behavior and interactions to clock phenotypes in vivo.

## Key facts

- **NIH application ID:** 10797991
- **Project number:** 3R35GM144110-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Andy LiWang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $73,810
- **Award type:** 3
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797991

## Citation

> US National Institutes of Health, RePORTER application 10797991, Temperature and metabolic compensation mechanisms in a circadian clock system (3R35GM144110-02S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10797991. Licensed CC0.

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