Friday, September 19, 2025 9/19/2025

Mechanisms controlling cell size and shape

Award Number: R35GM149248
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: 09/25/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Mechanisms controlling cell size and shape - PROJECT SUMMARY The overall goal of NIGMS-funded research in my lab is to define the molecular and cellular mechanisms that control cell size and shape. Defects in cell size and shape are associated with human diseases including cancer, so defining the underlying mechanisms can identify future therapeutic targets. We use the fission yeast S. pombe as a model system to study these fundamental processes. These rod-shaped eukaryotic cells grow by linear extension due to polarized secretion at growing cell tips, and enter mitosis at a highly reproducible size due to regulated activation of the ubiquitous cyclin-dependent kinase Cdk1. Decades of genetic screens have identified an extensive “parts list” for regulation of cell size and shape. Our current challenge is to assemble these parts into defined signaling networks that spatially control cell growth and activate Cdk1 in a size-dependent manner. For this work, we take a multidisciplinary approach that combines genetics, quantitative live-cell microscopy, phosphoproteomics, and biochemical reconstitution. In this proposal, we will address four key unanswered questions. First, how do cortical multiprotein clusters called “nodes” control fission yeast cell size at division? We discovered that nodes contain conserved cell cycle regulators including the protein kinases Cdr2, Cdr1, and Wee1, but we do not know the mechanisms of assembly or signal transduction within nodes. Second, what is the role of multiple cell cycle pathways in monitoring aspects of cell size such as volume and surface area? We will focus on the mitotic inducers Cdc25 and Cdc13/cyclin, with the goal of generating systems-level knowledge supported by mathematical modeling. Third, how do cell polarity mechanisms that function far away from the growing cell tips contribute to cell shape? We will exploit our recent discoveries that implicate RNA granules and SNARE protein clusters as novel “at-a-distance” regulators of cell polarity and shape. Fourth, how do cell size and shape influence spatial patterning of nodes in cells? We have identified cell tips, cortical anchors, and the nucleus as critical regulators of node positioning. We will combine genetic mutants with quantitative fluorescence microscopy and particle-based simulations to define the underlying design principles of this system. Based on extensive conservation of these pathways and processes between yeast and mammals, we fully expect that discoveries from our work will impact and guide future work in other organisms and biological systems.


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 = $585,939 )
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	3	8/7/2025	NON-COMPETING CONTINUATION	$585,939
2025	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	2	11/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $585,939

Issue Date FY: 2024 ( Subtotal = $657,776 )
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	2	8/27/2024	NON-COMPETING CONTINUATION	$585,939
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	1	8/23/2024	SUPPLEMENT FOR EXPANSION	$41,868
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	003	2	9/5/2024	NON-COMPETING CONTINUATION	$0
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	002	2	8/28/2024	SUPPLEMENT FOR EXPANSION	$29,969
														Subtotal = $657,776

Issue Date FY: 2023 ( Subtotal = $444,042 )
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	1	9/25/2023	NEW	$444,042
														Subtotal = $444,042

Grand Total All Awards = $1,687,757

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Mechanisms controlling cell size and shape

Award Number: R35GM149248

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: 09/25/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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