Monday, June 30, 2025 6/30/2025

Diversity Supplement to Mechanisms of Thin Filament Regulation by Myosin Binding Protein-C

Award Number: R01HL140925
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/17/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2023

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Diversity Supplement to Mechanisms of Thin Filament Regulation by Myosin Binding Protein-C - PROJECT SUMMARY The goal of this supplement is to support diversity in NIH missions through training and mentoring a graduate student with a disability. Research proposed under this supplement will be an integral part of the parent m-PI R01 (HL140925) and will be performed in the laboratory of Dr. Samantha Harris, one of the m-PIs, at the University of Arizona. Briefly, goals of the parent R01 are aimed at determining the structure-function relationships of cardiac myosin binding protein-C (cMyBP-C), an essential regulator of heart function, in its interactions with target proteins on the thin filaments of muscle sarcomeres. Specifically, high resolution cryo-EM reconstructions are created that yield information regarding the precise residues and binding interfaces for each of the N’-terminal subdomains of cMyBP-C with proteins on the thin filament (actin, tropomyosin, and troponin). The functional significance of these interactions is then determined using site directed mutagenesis to disrupt or strengthen these interactions followed by assessment of protein function in biochemical assays and force measurements in permeabilized (“skinned”) cardiac muscle cells. The proposed research will contribute to the aims of the parent award by 1) investigating the functional significance of amino acids in the “R-A-S-K” loop of domain C1 on force because these residues were shown by cryo-EM to activate the thin filament; 2) determining the functional effects of phosphorylation at each of the 3 canonical serines, individually and in aggregate, in the regulatory M-domain of cMyBP-C. These experiments are entirely within the scope of the parent proposal, but were chosen as ideal subprojects for mentoring and training a new graduate student to become proficient in technically challenging measurements of force in detergent- permeabilized muscle cells. Results from this funding will therefore increase inclusion and diversity while advancing the aims of the parent proposal by investigating key regulatory effects of cMyBP-C.


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 = -$1 )
2025	2022	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cardiovascular Diseases Research	001	4	4/24/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2022	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cardiovascular Diseases Research	000	4	4/24/2025	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cardiovascular Diseases Research	000	4	12/12/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $584,916 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	003	4	8/15/2022	SUPPLEMENT FOR EXPANSION	-$39,283
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	000	4	12/7/2021	NON-COMPETING CONTINUATION	$503,507
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	001	4	1/29/2022	SUPPLEMENT FOR EXPANSION	$64,747
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	002	4	6/8/2022	NON-COMPETING CONTINUATION	$55,945
														Subtotal = $584,916

Issue Date FY: 2021 ( Subtotal = $559,506 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	001	3	5/19/2021	NON-COMPETING CONTINUATION	$55,950
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	000	3	11/20/2020	NON-COMPETING CONTINUATION	$503,556
														Subtotal = $559,506

Issue Date FY: 2020 ( Subtotal = $559,557 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	000	2	12/20/2019	NON-COMPETING CONTINUATION	$531,579
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	001	2	3/8/2020	NON-COMPETING CONTINUATION	$27,978
														Subtotal = $559,557

Issue Date FY: 2019 ( Subtotal = $607,983 )
2019	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cardiovascular Diseases Research	000	1	12/17/2018	NEW	$607,983
														Subtotal = $607,983

Grand Total All Awards = $2,311,961

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Diversity Supplement to Mechanisms of Thin Filament Regulation by Myosin Binding Protein-C

Award Number: R01HL140925

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/17/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2023

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