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Structure and Mechanism of G-proteins and cell adhesion proteins in regulation of cell growth and motility

Award Number: R35GM134962
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Structure and Mechanism of G-proteins and cell adhesion proteins in regulation of cell growth and motility - Abstract The presented project is a comprehensive investigation encompassing two primary themes. The first theme revolves around the exploration of novel mechanisms governing the activation and signaling of guanine nucleotide-binding (G)-proteins, with a particular focus on the RAS superfamily and heterotrimeric Gα-proteins. Departing from conventional beliefs that G-protein activity is predominantly influenced by nucleotide cycling, recent findings challenge this paradigm. The project aims to delve into the regulation of inactive 'off' and active 'on' states of Gα-proteins by scrutinizing key allosteric networks within the Switch regions. Research objectives include elucidating interactions within the allosteric Switch network, investigating novel mechanisms controlling G-protein activation through pH modulation, and exploring the overlooked role of RAS-related proteins in mediating lipid kinase regulation. Employing a multidisciplinary approach that integrates computational, structural, biochemical, and cell biology methodologies, the project seeks to advance our understanding of G-protein regulation, contributing valuable insights for precision medicine strategies targeting G-protein-mediated pathologies. The second theme of the project centers on cell adhesion proteins, vinculin, and metavinculin. The investigation aims to unravel the individual and coordinated roles of these isoforms in regulating cell morphology, force transmission, and cell motility. Additionally, the project seeks to elucidate how metavinculin mutations, implicated in heart defects, disrupt adhesion site morphology and contractile force. Building on prior research into vinculin catch bonds with filamentous actin, the project expands molecular and functional studies to comprehend the collaborative roles of vinculin, metavinculin, and α-catenin in the directional and force-dependent regulation of adhesion morphology, force transmission, directed migration, and mechanosensitive diseases resulting from dysregulated mechanical cues. This dual-themed project employs a holistic and integrative approach, fostering a deeper understanding of cellular processes and providing a foundation for potential therapeutic interventions in diseases associated with G-protein and cell adhesion protein dysregulation.


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 = $602,153 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	6	1/16/2025	COMPETING CONTINUATION	$602,153
2025	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	5	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $602,153

Issue Date FY: 2024 ( Subtotal = $597,953 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	5	5/16/2024	NON-COMPETING CONTINUATION	$59,795
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	5	1/9/2024	NON-COMPETING CONTINUATION	$538,158
														Subtotal = $597,953

Issue Date FY: 2023 ( Subtotal = $613,585 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	002	4	6/27/2023	SUPPLEMENT FOR EXPANSION	$15,632
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	4	1/9/2023	NON-COMPETING CONTINUATION	$538,158
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	4	4/5/2023	NON-COMPETING CONTINUATION	$59,795
														Subtotal = $613,585

Issue Date FY: 2022 ( Subtotal = $597,953 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	3	1/14/2022	NON-COMPETING CONTINUATION	$538,158
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	3	6/24/2022	NON-COMPETING CONTINUATION	$59,795
														Subtotal = $597,953

Issue Date FY: 2021 ( Subtotal = $628,629 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	002	2	8/16/2021	SUPPLEMENT FOR EXPANSION	$30,676
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	2	1/28/2021	NON-COMPETING CONTINUATION	$538,158
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	2	2/12/2021	NON-COMPETING CONTINUATION	$59,795
														Subtotal = $628,629

Issue Date FY: 2020 ( Subtotal = $577,069 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	1	1/29/2020	NEW	$532,801
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	1	6/30/2020	SUPPLEMENT FOR EXPANSION	$44,268
														Subtotal = $577,069

Grand Total All Awards = $3,617,342

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Structure and Mechanism of G-proteins and cell adhesion proteins in regulation of cell growth and motility

Award Number: R35GM134962

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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