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Circadian regulation of brain and body in larval zebrafish

Award Number: R35GM146885
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: 07/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Circadian regulation of brain and body in larval zebrafish - PROJECT SUMMARY Circadian rhythms drastically alter animal behavior through diverse actions on cellular targets throughout the body. Disruptions of sleep-activity cycles account for a wide range of diseases affecting behavior, neurology, metabolism, and muscle physiology. This proposal presents a set of studies designed to understand the mechanisms and interactions of circadian effects on cells and systems spanning the body. Circadian rhythms manifest downstream of pacemakers via signaling molecules that act directly on targets to regulate physiology. Understanding how distinct targets are modified to achieve a constellation of physiological and behavioral rhythms is a major goal in chronobiological research. We study how neurons, muscles, and biomechanics interact in larval zebrafish, a tractable diurnal vertebrate, and our preliminary experiments suggest these animals experience a breadth of circadian changes far more diverse than previously known. Although the zebrafish is an imperfect model of sleep behavior, its clear circadian rhythms combined with its tractability for physiological, behavioral, and genetic approaches make it an ideal system for understanding how circadian rhythms organize and interact across cells and organs. We propose to define how diverse circadian effects on nervous system output and muscle physiology amount to complex behavioral output, by tracking and modeling zebrafish behavior and arousal across the diel cycle. We will manipulate light exposure to disentangle circadian and photic effects on target systems, and we will use computational models to understand how circadian effects interact to shape behavioral output. Furthermore, we will evaluate the breadth of circadian regulation of physiology across cellular targets by performing in vivo electrophysiology and functional imaging. Combining this approach with cellular- resolution transcriptional profiling enables us to define how circadian effector molecules signal divergently across targets. Finally, we will test for interactions across circadian targets by examining rhythms following focal lesions throughout the nervous system. Together these experiments will provide detailed information and models regarding the interaction of circadian effects across cells and systems.


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 = $382,090 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	4	5/8/2025	NON-COMPETING CONTINUATION	$382,090
														Subtotal = $382,090

Issue Date FY: 2024 ( Subtotal = $382,090 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	3	5/23/2024	NON-COMPETING CONTINUATION	$382,090
														Subtotal = $382,090

Issue Date FY: 2023 ( Subtotal = $632,090 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	2	6/27/2023	SUPPLEMENT FOR EXPANSION	$250,000
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	2	5/22/2023	NON-COMPETING CONTINUATION	$382,090
														Subtotal = $632,090

Issue Date FY: 2022 ( Subtotal = $382,090 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	1	7/11/2022	NEW	$382,090
														Subtotal = $382,090

Grand Total All Awards = $1,778,360

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Circadian regulation of brain and body in larval zebrafish

Award Number: R35GM146885

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: 07/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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