# Temperature and metabolic compensation mechanisms in a circadian clock system

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, MERCED · 2024 · $91,008

## 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:** 11096408
- **Project number:** 3R35GM144110-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Andy LiWang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $91,008
- **Award type:** 3
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11096408

## Citation

> US National Institutes of Health, RePORTER application 11096408, Temperature and metabolic compensation mechanisms in a circadian clock system (3R35GM144110-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11096408. Licensed CC0.

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