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Cell death pathway leading to vacuole permeabilization

Award Number: R21AI183596
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Cell death pathway leading to vacuole permeabilization - PROJECT SUMMARY Programmed cell death (self-induced) is intrinsic to cellular life, including unicellular species. However, cell death research has focused primarily on animal models to understand cancer, degenerative disorders, and developmental processes. In contrast, there is comparably little knowledge of how prokaryotic and eukaryotic microbes die, and cell death mechanisms in human fungal pathogens (multi- or unicellular) are nearly unstudied. Over a million fungal infections are diagnosed annually, many causing significant mortality, and resistance to conventional therapies continues to increase. Building on the principles of cell death discovered in the metazoan cell death field, we propose to characterize novel cell death pathways in unicellular fungal species using the tractable Saccharomyces cerevisiae model system. Targeted genetic approaches, cell biological and biochemical approaches will be used to dissect a vesicle trafficking cell death pathway in yeast that results in lysosome/vacuole membrane permeabilization and cell death, with implications for the human pathogen Cryptococcus neoformans. This new mechanistic understanding is intended to provide fundamental knowledge needed for the future development of new therapeutic strategies analogous to successes in targeted cancer therapy by inducing intrinsic cell death mechanisms.


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 = $198,547 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	2	12/23/2024	NON-COMPETING CONTINUATION	$198,547
														Subtotal = $198,547

Issue Date FY: 2024 ( Subtotal = $245,625 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	002	1	9/11/2024	NEW	$24,562
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	2/1/2024	NEW	$221,063
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	1	2/6/2024	NEW	$0
														Subtotal = $245,625

Grand Total All Awards = $444,172

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Cell death pathway leading to vacuole permeabilization

Award Number: R21AI183596

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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