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Candida albicans Target of Rapamycin in oxidative stress responses

Award Number: R21AI178693
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: 11/22/2024
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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Candida albicans Target of Rapamycin in oxidative stress responses - Abstract The goal of this proposal is to examine the role of Candida albicans Tor1 kinase and specifically, its least- conserved domain, N-terminal HEAT repeats, in enabling this fungal pathogen to withstand oxidative stress imposed by the host immune system. We showed that C. albicans cells lacking Tor1 N-terminal HEAT repeats, which are protein-protein interaction domains, are exquisitely hypersensitive to oxidative stress. They also dysregulate dedicated oxidative stress management systems of the fungus, and their metabolic output of intermediates required in redox homeostasis is defective. Tor1 point mutants that we recently engineered, show that these severe defects are not attributable to simple hypo- or hyperactivity of the kinase. Instead, these cells’ oxidative stress management defects appear to relate to functions residing in the N-terminal HEAT repeats. Notably, we found a core enzyme of C. albicans redox homeostasis, that is structurally and functionally completely different than its human counterpart, to be dysregulated in cells lacking Tor1 N-terminal HEAT repeats. We also found that depletion of this enzyme leads to starkly decreased TORC1 signaling even in conditions of ample nutrients and absent stress. We propose to define the interactions between Tor1 and its N-terminal HEAT repeats with dedicated C. albicans oxidative stress management 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: 2026 ( Subtotal = $222,500 )
2026	2026	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	11/26/2025	NON-COMPETING CONTINUATION	$222,500
														Subtotal = $222,500

Issue Date FY: 2025 ( Subtotal = $258,990 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	11/22/2024	NEW	$258,990
														Subtotal = $258,990

Grand Total All Awards = $481,490

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Candida albicans Target of Rapamycin in oxidative stress responses

Award Number: R21AI178693

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: 11/22/2024

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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