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Molecular mechanisms of bundled actin structure assembly by formins

Award Number: R01GM122787
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: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Molecular mechanisms of bundled actin structure assembly by formins - PROJECT SUMMARY The goal of this research is to understand how formins shape the architecture and dynamics of the actin cytoskeleton. Formins are a uniquely versatile family of actin regulatory proteins that stimulate both filament nucleation and elongation. Actin filaments assembled by formins are incorporated into a diverse set of higher- order structures that support essential cellular functions, including migration, division, and transport. Mammals express 15 formin isoforms, each of which possesses unique actin assembly properties and plays a specific role in cells. Consistent with this specialization, mutations in individual formin genes are linked to a broad range of diseases and pathologies, including neurological disorders, kidney disease, microcephaly, cardiomyopathy, and several cancers. However, despite their foundational roles as regulators of actin assembly, it is unknown how the polymerization activity of each formin isoform is tailored for the assembly of a specific actin structure. To bridge this gap in understanding, our goal is to establish how the broad range of formin activities influences actin network physiology and dynamics. Our central hypothesis is that formins direct the assembly and specialization of higher-order actin structures by generating binding sites for bundling and severing proteins at isoform-specific rates. We will use a combination of biophysical and cell biological approaches to test this hypothesis by pursuing three specific aims: (1) to elucidate the mechanism that underpins the adaptable polymerization activities of formins, (2) to investigate the effects of formin-mediated elongation on actin filament bundling, and (3) to assess the interdependent contributions of filament nucleation, elongation, and turnover to actin structure dynamics. Our work will establish at a molecular level how formins dynamically regulate the construction, specialization, and function of cytoskeletal structures that are essential for cellular viability and human development. In light of the diversity of formin isoforms, our results will generate fundamental insights into the molecular and temporal regulation of a large number of cellular processes. This will inform and guide our understanding of the molecular pathologies underlying a diverse set of human diseases linked to mutations in formin genes.


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: 2026 ( Subtotal = $317,041 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Biomedical Research and Research Training	001	9	3/17/2026	NON-COMPETING CONTINUATION	$31,704
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Biomedical Research and Research Training	000	9	1/14/2026	NON-COMPETING CONTINUATION	$285,337
														Subtotal = $317,041

Issue Date FY: 2025 ( Subtotal = $317,041 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Biomedical Research and Research Training	001	8	8/7/2025	NON-COMPETING CONTINUATION	$31,704
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	8	11/15/2024	NON-COMPETING CONTINUATION	$285,337
														Subtotal = $317,041

Issue Date FY: 2024 ( Subtotal = $317,041 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	003	7	7/23/2024	NON-COMPETING CONTINUATION	$31,704
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	002	7	11/22/2023	NON-COMPETING CONTINUATION	$285,337
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	001	6	11/7/2023	COMPETING CONTINUATION	$91,928
2024	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	5	11/7/2023	NON-COMPETING CONTINUATION	-$91,928
														Subtotal = $317,041

Issue Date FY: 2023 ( Subtotal = $317,041 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	001	6	12/15/2022	COMPETING CONTINUATION	$317,041
2023	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	5	12/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $317,041

Issue Date FY: 2021 ( Subtotal = $286,465 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	5	7/1/2021	NON-COMPETING CONTINUATION	$286,465
														Subtotal = $286,465

Issue Date FY: 2020 ( Subtotal = $286,536 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	4	7/14/2020	NON-COMPETING CONTINUATION	$286,536
														Subtotal = $286,536

Issue Date FY: 2019 ( Subtotal = $286,607 )
2019	2019	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	3	6/24/2019	NON-COMPETING CONTINUATION	$286,607
														Subtotal = $286,607

Issue Date FY: 2018 ( Subtotal = $286,676 )
2018	2018	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	2	6/14/2018	NON-COMPETING CONTINUATION	$286,676
														Subtotal = $286,676

Issue Date FY: 2017 ( Subtotal = $285,068 )
2017	2017	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	1	6/23/2017	NEW	$285,068
														Subtotal = $285,068

Grand Total All Awards = $2,699,516

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Molecular mechanisms of bundled actin structure assembly by formins

Award Number: R01GM122787

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: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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