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Cell Competition in Development and Homeostasis

Award Number: R01CA284362
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Cell Competition in Development and Homeostasis - A process of cell competition can remove cells that differ genetically from neighboring cells in the same tissues. Cell competition helps to eliminate sporadic aneuploid cells that have abnormal chromosome numbers. Aneuploidy contributes to almost all carcinogenesis and is a hallmark of aging, contributing to cellular senescence. The current project investigates the mechanisms by which genes that encode ribosomal proteins, by virtue of their wide distribution in the genome and stoichiometric requirement for ribosome biogenesis, are used as sensors for altered cellular chromosome content, using fruitflies as a genetic model system. Importantly, cells with single mutations in ribosomal protein genes can also be recognized and removed from developing tissues by the process of cell competition with nearby normal cells, related to the elimination of aneuploid cells. This project will further define the molecular mechanisms of cell competition pathways by gain and loss of function genetics targeted specifically to aneuploid cells within otherwise normal tissues, and characterize the alterations in gene expression that result from cell competition on a single cell level. The relationship of specific chromosome gains and losses to tumor formation will be defined. The mechanisms whereby the p53 protein protects the genome from progressive genome damage, and the route by which genomic changes accumulate in the progression towards cancer, will be elucidated. These studies aim to define the molecular basis for the cellular recognition and elimination of aneuploid cells in developing tissues, its role in maintaining genome integrity at the tissue level by selection against abnormal cells, and its role in tumor surveillance and the development of cancers.


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 = $408,913 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Cancer Cause and Prevention Research	000	11	7/29/2025	NON-COMPETING CONTINUATION	$408,913
														Subtotal = $408,913

Issue Date FY: 2024 ( Subtotal = $408,913 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Cancer Cause and Prevention Research	000	10	8/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$408,913
														Subtotal = $408,913

Grand Total All Awards = $817,826

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Cell Competition in Development and Homeostasis

Award Number: R01CA284362

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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