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Microbial regulation of vertebrate circadian clocks

Award Number: R35GM147509
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Microbial regulation of vertebrate circadian clocks - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $384,099 )
2025	2025	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	4	6/17/2025	NON-COMPETING CONTINUATION	$384,099
														Subtotal = $384,099

Issue Date FY: 2024 ( Subtotal = $384,099 )
2024	2024	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	3	6/10/2024	NON-COMPETING CONTINUATION	$384,099
														Subtotal = $384,099

Issue Date FY: 2023 ( Subtotal = $384,099 )
2023	2023	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	2	6/20/2023	NON-COMPETING CONTINUATION	$384,099
														Subtotal = $384,099

Issue Date FY: 2022 ( Subtotal = $384,099 )
2022	2022	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	1	7/21/2022	NEW	$384,099
														Subtotal = $384,099

Grand Total All Awards = $1,536,396

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Microbial regulation of vertebrate circadian clocks

Award Number: R35GM147509

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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