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Signal sensing, hyphal development and pathognesis of Candida albicans

Award Number: R01GM117111
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: 02/01/2017
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Signal sensing, hyphal development and pathognesis of Candida albicans - PROJECT SUMMARY Candida albicans is one of the most frequently isolated fungal pathogens of humans. A critical virulence attribute of C. albicans is its morphogenetic plasticity. In response to host environmental cues, this fungus can grow as yeast, pseudohyphal, and hyphal forms. Mutants that are defective in hyphal formation display attenuated virulence in animal models of systemic candidiasis. Our long-term goal is to understand the signaling pathways that govern C. albicans morphogenesis. Studies from our laboratory show that hyphal development consists of two temporally linked phases, initiation and maintenance. Initiation requires the Ras-cAMP-protein kinase A (PKA) pathway that regulates the rapid but temporary disappearance of the Nrg1 transcriptional repressor of hyphal development. Maintenance requires the Brg1 transcription factor-mediated promoter chromatin remodeling of hypha-specific genes in response to nutrient limitation in air or stabilization of the Ume6 transcriptional activator under hypoxia and hypercapnia. We have uncovered conserved sensors for N-actylglucosamine (GlcNAc), CO2, and hypoxia that are linked to hyphal development. In the current proposal, we will extend these studies through the following aims: Aim 1. Investigate Nrg1 down- regulation during hyphal initiation. Aim 2. Examine signaling pathways for hyphal morphogenesis inside macrophage. Aim 3. Identify transcriptional programs under hypoxia and physiological CO2. This proposal will gain molecular insights into how host signals are sensed by C. albicans to control hyphal development during infection, which is critically important in understanding its pathogenicity. The results of these in-depth investigations will provide new insight into the mechanisms that govern hyphal initiation and maintenance in an important fungal pathogen, and will serve as the foundation for novel therapeutic strategies against C. albicans. Furthermore, the signaling pathways to be examined in this application are likely conserved among diverse fungal pathogens. Data from these studies will provide insight into signaling pathways that govern virulence in other fungi.


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: 2024 ( Subtotal = $480,280 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Biomedical Research and Research Training	001	8	7/23/2024	NON-COMPETING CONTINUATION	$48,027
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Biomedical Research and Research Training	000	8	3/14/2024	NON-COMPETING CONTINUATION	$432,253
														Subtotal = $480,280

Issue Date FY: 2023 ( Subtotal = $491,402 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Biomedical Research and Research Training	001	7	5/16/2023	SUPPLEMENT FOR EXPANSION	$11,122
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Biomedical Research and Research Training	000	7	3/9/2023	NON-COMPETING CONTINUATION	$480,280
														Subtotal = $491,402

Issue Date FY: 2022 ( Subtotal = $480,280 )
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	001	6	8/1/2022	NON-COMPETING CONTINUATION	$48,032
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	000	6	3/25/2022	NON-COMPETING CONTINUATION	$432,248
														Subtotal = $480,280

Issue Date FY: 2021 ( Subtotal = $497,477 )
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	002	5	5/3/2021	SUPPLEMENT FOR EXPANSION	$17,197
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	004	5	7/30/2021	COMPETING CONTINUATION	$37,195
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	001	5	3/2/2021	COMPETING CONTINUATION	$480,280
2021	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	000	4	2/22/2021	NON-COMPETING CONTINUATION	$0
2021	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	003	4	7/30/2021	NON-COMPETING CONTINUATION	-$37,195
														Subtotal = $497,477

Issue Date FY: 2020 ( Subtotal = $438,041 )
2020	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	000	4	1/7/2020	NON-COMPETING CONTINUATION	$438,041
														Subtotal = $438,041

Issue Date FY: 2019 ( Subtotal = $482,580 )
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	001	3	7/30/2019	SUPPLEMENT FOR EXPANSION	$44,539
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	000	3	1/11/2019	NON-COMPETING CONTINUATION	$438,041
														Subtotal = $482,580

Issue Date FY: 2018 ( Subtotal = $493,274 )
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	002	2	8/1/2018	SUPPLEMENT FOR EXPANSION	$55,233
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	000	2	1/31/2018	NON-COMPETING CONTINUATION	$394,236
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	001	2	5/10/2018	NON-COMPETING CONTINUATION	$43,805
														Subtotal = $493,274

Issue Date FY: 2017 ( Subtotal = $451,666 )
2017	2017	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Biomedical Research and Research Training	000	1	1/17/2017	NEW	$451,666
														Subtotal = $451,666

Grand Total All Awards = $3,815,000

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Signal sensing, hyphal development and pathognesis of Candida albicans

Award Number: R01GM117111

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: 02/01/2017

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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