Tuesday, June 24, 2025 6/24/2025

Cell-cycle-dependent cell polarity control

Award Number: R01GM136847
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: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Cell-cycle-dependent cell polarity control - PROJECT SUMMARY/ABSTRACT Polarized cells in retain their shape in every cell cycle and this is essential to their proper function. Anomalies in polarized cell shape can result in cancer, metabolic disorders, and loss of tissue integrity. Here, we will investigate a long-standing question of how cells consistently regain their polarity after each round of division. This investigation will be conducted using the fission yeast, Schizosaccharomyces pombe model system that provides many well characterized genetic tools to manipulate conserved proteins that influence cell shape following division. Cdc42 is the major regulator of polarized growth. In fission yeast, cells halt polarized Cdc42 activation and consequent growth at the cell ends during mitosis. After completion of division, these cell ends resume Cdc42 activation and cell growth. After division, Cdc42 activation and polarized growth always resumes in a monopolar manner from the old end that pre-exists from the previous generation. The cell transitions to bipolar growth when Cdc42 activation also resumes at the newly formed cell end in the G2 phase of the cell cycle. Our preliminary data indicate that resumption of Cdc42 activation at the old end after division and transition to bipolar activation in G2 are cell cycle dependent. Our central hypothesis is that Cdc42 is differentially regulated at the cell ends by distinct cell-cycle-dependent cues to establish the cell polarization pattern. We will test this hypothesis by pursuing the following specific aims, [1] Determine how Cdc42 activation resumes at the cell ends in the G1/S phase; [2] Elucidate how a memory of growth from the previous cell cycle enables the pre-existing old end to initiate Cdc42 activation first; [3] Explain how the transition from monopolar to bipolar growth occur in G2 phase. With this project we expect to mechanistically understand how Cdc42 activation and associated growth patterns are modulated in different cell cycle stages. We will examine how signals from one cell cycle inform the growth pattern in the next generation. This will provide much needed insights into the principles that preserve polarized cell shape in complex systems. Due to the conserved nature of the proteins involved in this investigation, we expect that our findings will be relevant cell shape control in higher eukaryotes and provide potential therapeutic or diagnostic targets for diseases such as cancer.


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 = $92,179 )
2025	2022	TRUSTEES OF BOSTON COLLEGE	140 COMMONWEALTH AVE	CHESTNUT HILL	MA	02467	MIDDLESEX	USA	Biomedical Research and Research Training	001	4	1/8/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$92,178
2025	2022	TRUSTEES OF BOSTON COLLEGE	140 COMMONWEALTH AVE	CHESTNUT HILL	MA	02467	MIDDLESEX	USA	Biomedical Research and Research Training	000	4	10/22/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
														Subtotal = $92,179

Issue Date FY: 2024 ( Subtotal = $296,672 )
2024	2024	TRUSTEES OF BOSTON COLLEGE	140 COMMONWEALTH AVE	CHESTNUT HILL	MA	02467	MIDDLESEX	USA	Biomedical Research and Research Training	003	6	7/23/2024	NON-COMPETING CONTINUATION	$29,679
2024	2024	TRUSTEES OF BOSTON COLLEGE	140 COMMONWEALTH AVE	CHESTNUT HILL	MA	02467	MIDDLESEX	USA	Biomedical Research and Research Training	002	6	2/29/2024	NON-COMPETING CONTINUATION	$267,107
2024	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	2	11/6/2023	NON-COMPETING CONTINUATION	-$114
2024	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	001	2	11/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $296,672

Issue Date FY: 2023 ( Subtotal = $232,949 )
2023	2023	TRUSTEES OF BOSTON COLLEGE	140 COMMONWEALTH AVE	CHESTNUT HILL	MA	02467	MIDDLESEX	USA	Biomedical Research and Research Training	004	5	3/3/2023	NON-COMPETING CONTINUATION	$311,389
2023	2022	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	002	3	3/1/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	006	3	5/15/2023	NON-COMPETING CONTINUATION	-$1
2023	2022	TRUSTEES OF BOSTON COLLEGE	140 COMMONWEALTH AVE	CHESTNUT HILL	MA	02467	MIDDLESEX	USA	Biomedical Research and Research Training	003	4	3/2/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2022	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	3	2/10/2023	NON-COMPETING CONTINUATION	-$299,373
2023	2022	TRUSTEES OF BOSTON COLLEGE	140 COMMONWEALTH AVE	CHESTNUT HILL	MA	02467	MIDDLESEX	USA	Biomedical Research and Research Training	001	4	2/13/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$312,998
2023	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	005	2	5/15/2023	NON-COMPETING CONTINUATION	-$92,064
														Subtotal = $232,949

Issue Date FY: 2022 ( Subtotal = $299,374 )
2022	2022	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	000	3	2/11/2022	NON-COMPETING CONTINUATION	$269,436
2022	2022	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	001	3	7/28/2022	NON-COMPETING CONTINUATION	$29,938
														Subtotal = $299,374

Issue Date FY: 2021 ( Subtotal = $297,857 )
2021	2021	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	000	2	2/16/2021	NON-COMPETING CONTINUATION	$297,857
														Subtotal = $297,857

Issue Date FY: 2020 ( Subtotal = $327,557 )
2020	2020	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	000	1	2/21/2020	NEW	$327,557
														Subtotal = $327,557

Grand Total All Awards = $1,546,588

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Cell-cycle-dependent cell polarity control

Award Number: R01GM136847

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: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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