# Regulation and Significance of Sustained Circadian Oscillations

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $306,052

## Abstract

Project Summary/Abstract:
 Circadian (daily) rhythms are a crucial component of human health that regulates sleep,
alertness, hormones, metabolism, and many other biological processes. The fascination of this
phenomenon is to explain how a biochemical mechanism (i) can robustly sustain a long period
(~24 h) oscillation whose frequency keeps time so precisely, and (ii) enhance fitness in the
natural environment. These questions remain critically important unanswered issues in the
circadian rhythms field. For example, the adaptive value is not clear for the most obvious
circadian characteristic–a robust self-sustained oscillation in constant conditions. If “anticipation”
of future temporal events (e.g., dawn, dusk, etc.) is the goal of circadian timekeepers, why is a
temperature-compensated “hourglass timer” that is initiated by dawn or dusk not sufficient? And
yet evolution ubiquitously selected an oscillator that sustains itself in non-natural continuous as
the timekeeper for regulating daily processes, and this characteristic forms a core defining
property of circadian rhythms. The overall goal of this project is to determine which
characteristics of rhythmic environments provide selective pressures that direct cellular
organization of gene expression and metabolism to promote properties of circadian
timekeeping. Identifying the selective pressures & evolutionary steps that can lead to biological
timekeeping will enable a more profound understanding of circadian mechanisms and the
way(s) they might be reinforced to aid human health and performance.
 The unique characteristics of model systems will be harnessed to attain the goal of this
project by a multifaceted approach. First, in free-living organisms, fitness tests, transcriptomics,
and biochemistry will determine if metabolic conditions dictate whether sustained oscillators are
necessarily adaptive. Second, the temporal dimensions of host/microbiome relations will be
manipulated to ascertain if the gut microbiome is under active selection for timekeeping ability.
Finally, a novel experimental selection approach will identify which environmental pressures are
capable of evolving circadian clocks.
 The answers to these questions will help us to better understand general principles of
fundamental circadian organization and rhythmic regulation of metabolism; this understanding
can help us to better design therapies for disorders in which circadian clocks are implicated.

## Key facts

- **NIH application ID:** 9976535
- **Project number:** 5R01GM107434-08
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** CARL Hirschie JOHNSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $306,052
- **Award type:** 5
- **Project period:** 2013-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976535

## Citation

> US National Institutes of Health, RePORTER application 9976535, Regulation and Significance of Sustained Circadian Oscillations (5R01GM107434-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976535. Licensed CC0.

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