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Mechanisms of cell size determination by the mitotic cyclin Cdc13

Award Number: F31GM156081
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Mechanisms of cell size determination by the mitotic cyclin Cdc13 - PROJECT SUMMARY Eukaryotic cells tightly control their size to maintain proper cell physiology. Defects in cell size control can lead to developmental infidelity and disease. One mechanism for accurate cell size control is the coupling of cell growth and division. We use the fission yeast, Schizosaccharomyces pombe, which has a reproducible rod shape and strong genetic tools to study cell size control. In fission yeast, a cell size checkpoint delays entry into mitosis (the G2/M transition) until cells have grown to a critical size threshold. This checkpoint acts through activation of the cyclin-dependent kinase Cdk1 in complex with its cyclin subunit Cdc13. Recent work has shown that the nuclear concentration of Cdc13/cyclin increases over time, providing a mechanism to promote increased Cdk1 activity as cells grow. Nutrient limitation is known to reduce cell growth rate and cell size at division, meaning that the size control system monitors and responds to nutrient levels. It is not known how the Cdc13 time-dependent nuclear accumulation for cell size control is regulated under normal and modified growth conditions. The central hypothesis is that two factors are regulated by nutrient availability which connects size and the environment: time-dependent accumulation of Cdc13 in the nucleus and the threshold concentration of Cdc13 that promotes mitotic entry. To test this hypothesis, I will first determine the regulatory mechanisms of Cdc13 nuclear accumulation by measuring rates of nuclear import, nuclear export, and degradation. I will utilize a combination of live-cell microscopy techniques including photobleaching and photoconversion methods. Second, I will define how altered nutrient limitation modulates Cdc13 nuclear accumulation and its regulation. I will quantify the nuclear accumulation of Cdc13 under different nutrient conditions, as well as explore the role of the nutrient sensing pathways, such as AMPK and Greatwall-Endosulfine, in setting a PP2A threshold for the control of Cdc13 nuclear accumulation. The proposed work will establish a systems-level understanding of cell size control and how it can be tuned by environmental conditions. In addition to the significant scientific contributions this work will make in the field of cell size control, I will also gain invaluable technical skills, knowledge, and communication experience.


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 = $50,102 )
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	2	1/9/2026	NON-COMPETING CONTINUATION	$49,538
2026	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	1	1/8/2026	NEW	$564
														Subtotal = $50,102

Issue Date FY: 2025 ( Subtotal = $48,974 )
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	1	11/25/2024	NEW	$0
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	1	11/25/2024	NEW	$48,974
														Subtotal = $48,974

Grand Total All Awards = $99,076

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Mechanisms of cell size determination by the mitotic cyclin Cdc13

Award Number: F31GM156081

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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