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Roles of C. albicans white-opaque regulators in biofilm and virulence

Award Number: R21AI185250
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: 06/11/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Roles of C. albicans white-opaque regulators in biofilm and virulence - Candida albicans is among the most significant human fungal pathogens. It can undergo two well-studied cell type transitions, yeast-hyphal and white-opaque. The yeast-hyphal transition is required for both virulence and biofilm formation; the white-opaque transition is required for mating. Each transition occurs in distinct growth conditions, and the regulatory network that governs the transitions seems structured to ensure that the transitions are mutually exclusive. Our recent studies indicate that two white-opaque regulators, Wor1 and Wor3, have unexpected positive roles in biofilm and hypha formation and in host cell damage and virulence. Importantly, we find that Wor3-regulated genes are not the typical hypha-associated genes that are already known to promote biofilm, hyphae, and virulence. Our objective is to use this newly discovered role of Wor3 to define new mediators of biofilm and hypha formation and virulence, and to use the analytical strategies that were successful for Wor3 to test the roles of other white-opaque regulators in these central pathogenicity traits. The analysis of Wor3 has exploited two genetic interaction strategies. One is an overexpression- rescue assay, in which we ask if increased expression of one gene can overcome the phenotypic defect of a deletion mutant in another gene. The second is a synthetic defect assay, in which as ask if a deletion mutation in one gene causes a unique or prominent phenotype when combined with a deletion mutation in another gene. Our proposed studies apply these assays systematically to the other Wor regulators in combination with well-known regulators of hypha and biofilm formation to define new gene functions and targets. Our specific aims are to define functional roles of Wor regulators in biofilm and hypha formation, and to define functional roles of Wor regulators in host interaction and virulence. Our longer-term goal is to use novel targets of Wor regulators to define new determinants of pathogenicity and biofilm persistence.


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 = $195,312 )
2025	2025	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	2	5/13/2025	NON-COMPETING CONTINUATION	$195,312
														Subtotal = $195,312

Issue Date FY: 2024 ( Subtotal = $245,812 )
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	6/11/2024	NEW	$221,231
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$24,581
														Subtotal = $245,812

Grand Total All Awards = $441,124

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Roles of C. albicans white-opaque regulators in biofilm and virulence

Award Number: R21AI185250

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: 06/11/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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