Tuesday, November 4, 2025 11/4/2025

In Vivo Genetic Analysis of Compartmentalized Cell Elimination

Award Number: R35GM142489
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: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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In Vivo Genetic Analysis of Compartmentalized Cell Elimination - Project Summary/Abstract Programmed cell death (PCD) and has vital roles in organismal health and is essential to normal development. Apoptosis is genetically programmed and mutations in regulatory genes contribute greatly to cancer therapy resistance. Timely clearance of cellular debris following cell death is also critical as defects lead to inflammation and are linked to autoimmune disease. Most cells in the body are highly differentiated and have intricate morphologies. This presents challenges in the execution of cell death and clearance, as the subcellular architecture and microenvironment of different compartments of the same cell may differ vastly. Complex cells can die as a whole or in part. In the case of region-specific degeneration, cellular extensions are exclusively dismantled leaving the rest of the cell intact. For neurons, such pruning is important in establishing appropriate connectivity and thus for proper brain function. The central question addressed here is how morphologically complex cells are eliminated. The C. elegans tail-spike cell is a valuable model to study complex cell degeneration, dying through an elaborate, likely universal, compartment-specific program of cell death during embryonic development. We have termed this remarkable program Compartmentalized Cell Elimination (CCE), which also occurs in a set of sex-specific neurons, suggesting this may be a universal program of death. The tail-spike cell also shows differential genetic regulation at the levels of both compartmental killing and clearance. As such, a study of this single cell can provide insights on many facets of cell elimination. This proposal leverages the fact that the tail-spike cell can be studied in its native context in the living animal as well as the facile genetics of C. elegans to tackle three broadly related overarching questions: How does mitochondrial trafficking influence cell process elimination? What novel genes govern CCE and hence cell death and removal broadly? What novel genes regulate CCE in other complex cells, such as neurons? We will perform advanced cell biological and genetic studies to address these questions. The proposed experiments, by illuminating fundamental principles of basic cell biology, will advance the field of cell death in several ways. They will identify novel regulators of PCD and clearance; they hold the potential to help devise targeted therapies against cell-death-related disease, including cancer, neurodegeneration, immune and developmental disorders.


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 = $404,783 )
2025	2025	UNIVERSITY OF TEXAS AT ARLINGTON	701 S NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	001	5	7/31/2025	NON-COMPETING CONTINUATION	$373,823
2025	2025	UNIVERSITY OF TEXAS AT ARLINGTON	701 S NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	4	1/20/2025	SUPPLEMENT FOR EXPANSION	$30,960
														Subtotal = $404,783

Issue Date FY: 2024 ( Subtotal = $380,887 )
2024	2024	UNIVERSITY OF TEXAS AT ARLINGTON	701 S NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	001	4	7/15/2024	NON-COMPETING CONTINUATION	$374,356
2024	2024	UNIVERSITY OF TEXAS AT ARLINGTON	701 S NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	002	4	7/16/2024	SUPPLEMENT FOR EXPANSION	$5,714
2024	2024	UNIVERSITY OF TEXAS AT ARLINGTON	701 S NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	3	5/2/2024	SUPPLEMENT FOR EXPANSION	$817
														Subtotal = $380,887

Issue Date FY: 2023 ( Subtotal = $698,130 )
2023	2023	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	2	5/3/2023	SUPPLEMENT FOR EXPANSION	$8,303
2023	2023	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	003	3	9/7/2023	SUPPLEMENT FOR EXPANSION	$249,619
2023	2023	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	002	3	5/9/2023	SUPPLEMENT FOR EXPANSION	$65,345
2023	2023	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	001	3	5/8/2023	NON-COMPETING CONTINUATION	$374,863
														Subtotal = $698,130

Issue Date FY: 2022 ( Subtotal = $440,690 )
2022	2022	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	001	2	7/21/2022	SUPPLEMENT FOR EXPANSION	$65,345
2022	2022	UNIVERSITY OF TEXAS AT ARLINGTON	400 S CORN ST	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	2	5/17/2022	NON-COMPETING CONTINUATION	$375,345
														Subtotal = $440,690

Issue Date FY: 2021 ( Subtotal = $375,805 )
2021	2021	UNIVERSITY OF TEXAS AT ARLINGTON	400 S CORN ST	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	1	7/23/2021	NEW	$375,805
														Subtotal = $375,805

Grand Total All Awards = $2,300,295

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In Vivo Genetic Analysis of Compartmentalized Cell Elimination

Award Number: R35GM142489

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: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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