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Regulation of exercise physiology by mammalian cryptochromes

Award Number: R01DK112927
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/07/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2021

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Regulation of exercise physiology by mammalian cryptochromes - 7. Project Summary/Abstract Our previous studies identified the circadian clock component cryptochromes (CRY1 and CRY2) as nutrient responsive transcriptional regulators by virtue of their susceptibility to phosphorylation by AMP-activated protein kinase (AMPK). We have also described a function of CRY1 and CRY2 as diurnally active repressors of the glucocorticoid receptor, a prototypical member of a large family of transcriptional regulators known as nuclear hormone receptors (NRs). NRs are broadly important in modulating metabolic physiology and one member of this family, the so-called peroxisome proliferator activated receptor delta (PPARδ) has been established as a critical driver of exercise capacity. We describe in our preliminary data here that CRY1 and CRY2 can repress PPARδ and genetic deletion of Cry1 and Cry2 ubiquitously and throughout development results in enhanced sprint exercise capacity. In the course of our studies, we have generated unique tools and expertise that enable us to use biochemical, genetic, molecular and physiological approaches to further elucidate the roles of CRY1 and CRY2 in the regulation of PPARδ and of exercise physiology in the following specific aims: 1) Does skeletal muscle drive enhanced exercise capacity in Cry1/2-deficient mice? 2) How does AMPK-mediated CRY1 phosphorylation impact exercise? and 3) What is the impact of Cry1/2 deletion or mutation on skeletal muscle cellular metabolism? Advancing our functional understanding of these interactions may highlight new therapeutic and regulatory strategies for preventing and/or treating disease.


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: 2022 ( Subtotal = $0 )
2022	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/24/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $416,667 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/13/2020	NON-COMPETING CONTINUATION	$375,000
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	2/8/2021	NON-COMPETING CONTINUATION	$41,667
														Subtotal = $416,667

Issue Date FY: 2020 ( Subtotal = $416,667 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/3/2019	NON-COMPETING CONTINUATION	$375,000
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	2/10/2020	NON-COMPETING CONTINUATION	$41,667
														Subtotal = $416,667

Issue Date FY: 2019 ( Subtotal = $416,667 )
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/29/2018	NON-COMPETING CONTINUATION	$416,667
														Subtotal = $416,667

Issue Date FY: 2018 ( Subtotal = $437,500 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/7/2017	NEW	$437,500
														Subtotal = $437,500

Grand Total All Awards = $1,687,501

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Regulation of exercise physiology by mammalian cryptochromes

Award Number: R01DK112927

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/07/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2021

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