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Regulation of Candida albicans Pathogenesis by Protein Kinase and Transcription Factor Networks

Award Number: R01AI177254
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: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Regulation of Candida albicans Pathogenesis by Protein Kinase and Transcription Factor Networks - PROJECT SUMMARY Candida albicans is both a component of the human mycobiome as well as one of the most important human fungal pathogens, capable of causing disease in both immunocompetent and immunocompromised people. The pathogenic cycle that leads to invasive C. albicans disease can be divided into three steps: 1) transition from mucosal colonization to sub-epithelial invasion; 2) filamentous morphogenesis within the sub-epithelium leading to tissue damage; and 3) intravascular dissemination to target organs. Infections that stop after the first two steps lead to mucosal diseases such as oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis while those that progress to the third step cause life-threating candidemia and deep organ disease. Although all three steps are required for the development of invasive disease, the third has been the most extensively studied through the widely used tail-vein inoculation mouse model of disseminated infection. In this application, we propose to use our barcoded collections of transcription factor (TF) and protein kinase (PK) mutants in competitive fitness assays to genetically define the global regulatory networks and key downstream effectors required for OPC mucosal infection (Aim 1). This aim will be facilitated by our recent development of an in vivo RNA-seq approach to characterize the transcriptional profile of C. albicans during OPC. In Aim 2, we will characterize the functions of the TF networks and identify the upstream PK signaling pathways that regulate in vivo filamentation. We will identify PK substrates critical for in vivo filament initiation and elongation. The successful execution of these aims will provide an unprecedentedly detailed in vivo profile of the regulatory mechanisms for the first two steps in C. albicans pathogenesis. Since PKs have emerged as important therapeutic targets across multiple areas of medicine, identification of PK networks with critical roles in C. albicans pathogenesis also holds promise to provide new insights with relevance to antifungal drug development.


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 = $739,862 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	2	1/17/2025	NON-COMPETING CONTINUATION	$739,862
														Subtotal = $739,862

Issue Date FY: 2024 ( Subtotal = $751,293 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	1	2/26/2024	NEW	$677,552
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	001	1	9/3/2024	NEW	$73,741
														Subtotal = $751,293

Grand Total All Awards = $1,491,155

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Regulation of Candida albicans Pathogenesis by Protein Kinase and Transcription Factor Networks

Award Number: R01AI177254

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: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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