# Microbial regulation of vertebrate circadian clocks

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2022 · $384,099

## Abstract

Project Summary/Abstract
Within each cell, a robust molecular clock is established by transcription-translation feedback loops driven by
the transcriptional activation complex CLOCK:BMAL1 and the repressors PER (period) and CRY (cryptochrome)
that turn CLOCK:BMAL1 “off”. The molecular clock controls daily oscillations in the expression of over 40% of
the genome to synchronize host physiology with the external environment. These oscillations are self-sustaining
on the cellular level: circadian rhythms persist with similar timing even when all external cues are removed, but
will align with external cues when present, a feature called entrainment. In mammals, induction of the circadian
repressor PER is a universal first step in the entrainment. Microbes are ubiquitous in our environment and
undergo daily fluctuations correlated with the 24-hour solar cycle, but it is not known how microbial exposure
impacts circadian rhythms. This research will explore how microbial concentration affects cellular signaling
cascades responsible for entrainment and will define novel innate regulators of the clock. In addition, these
studies will leverage the genetic and experimental tractability of zebrafish to perform high throughput, real time
kinetics of circadian responses in vivo. The ability to do whole body, non-invasive imaging in zebrafish has
significant advantages over established murine models and is particularly advantageous for migratory
populations such as immune cells. Furthermore, as a non-mammalian, cold-blooded vertebrate, the study of
clocks in zebrafish also represents an incredible opportunity to bridge the evolutionary gap between the most
well characterized animal systems: Drosophila (invertebrate) and mice (vertebrate, mammal). Together, this
research will advance our fundamental understanding of vertebrate circadian clocks and how it integrates
information about microbial stimulation to entrain cellular clocks at the molecular level.

## Key facts

- **NIH application ID:** 10500663
- **Project number:** 1R35GM147509-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Jacqueline Misum Kimmey
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,099
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10500663

## Citation

> US National Institutes of Health, RePORTER application 10500663, Microbial regulation of vertebrate circadian clocks (1R35GM147509-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10500663. Licensed CC0.

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