Tuesday, March 10, 2026 3/10/2026

Transcriptional Regulation of C. albicans Cell Fate and Host Interactions

Award Number: R01AI081704
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: 08/01/2010
PERIOD OF PERFORMANCE END DATE: 07/31/2027

Group Awards By:

View Award Description

Transcriptional Regulation of C. albicans Cell Fate and Host Interactions - Project Summary Candida albicans is a frequent commensal of the human microbiota and an important opportunistic pathogen. This fungus is chameleon-like in its ability to grow in alternative cellular states and different morphological forms, and this plasticity is critical for infection of diverse niches in the body. Here, we examine the transcriptional regulation of cell fate decisions that drive key developmental programs in C. albicans including filamentation, biofilm formation, and phenotypic switching. Each of these programs contributes to the ability of this fungus to colonize and/or cause disease in the mammalian host. Previous studies have identified multiple transcription factors (TFs) that regulate these developmental programs and showed that they act together in highly coordinated networks to drive gene expression. However, a major knowledge gap exists as to how cell fate-defining TFs act together in a coordinated manner rather than as individual entities. To address this gap, we highlight preliminary data revealing that network TFs can undergo liquid-liquid phase separation (LLPS) and demonstrate that this process enables the formation of complexes containing multiple network TFs. We further show that phase separation is driven by prion-like domains (PrLDs) present in each TF and, critically, that targeted mutation of these domains can abolish both LLPS and TF function. To build on these exciting observations, experiments outlined in Aim 1 will determine how the composition of PrLDs promotes LLPS and the formation of multifactorial complexes in vitro and in cells. We also address how changes in LLPS relate to the function of C. albicans TFs within key networks, including those controlling phenotypic switching and biofilm formation. In Aim 2, we will identify additional regulators of C. albicans cell fate using an overexpression library covering all TFs in the C. albicans genome. Preliminary data indicates that multiple novel regulators can be uncovered by this approach, and newly identified TFs will be integrated into existing transcriptional networks using a variety of approaches including the use of complex haploinsufficiency (CHI) analysis. In Aim 3, we examine how phase separation of C. albicans TFs impacts their function during commensalism and pathogenesis by testing mutant TFs in murine models of infection. These experiments will be facilitated by a barcode sequencing (barcode-SEQ) approach in which multiple strains can be evaluated in parallel for their competitive fitness. Together, these studies will lead to new insights into the fundamental mechanisms by which transcription factors regulate cell fate decisions in C. albicans, with an emphasis on how LLPS enables the formation of functional, multifactorial TF complexes. We will also identify novel TFs in these networks and test these TFs for their role in infectivity. Given the central role of TFs in regulating C. albicans cell fate, these studies will identify new targets for therapeutic intervention against this important human pathobiont.


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 = $478,500 )
2025	2025	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	14	7/18/2025	NON-COMPETING CONTINUATION	$478,500
														Subtotal = $478,500

Issue Date FY: 2024 ( Subtotal = $478,500 )
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	13	7/17/2024	NON-COMPETING CONTINUATION	$478,500
2024	2020	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	10	2/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $478,500

Issue Date FY: 2023 ( Subtotal = $478,500 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	12	7/20/2023	NON-COMPETING CONTINUATION	$478,500
														Subtotal = $478,500

Issue Date FY: 2022 ( Subtotal = $478,500 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	002	11	9/19/2022	COMPETING CONTINUATION	$478,500
2022	2020	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	10	1/18/2022	NON-COMPETING CONTINUATION	$0
2022	2020	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	10	9/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $478,500

Issue Date FY: 2020 ( Subtotal = $406,250 )
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	10	1/27/2020	NON-COMPETING CONTINUATION	$406,250
														Subtotal = $406,250

Issue Date FY: 2019 ( Subtotal = $406,250 )
2019	2019	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	9	1/16/2019	NON-COMPETING CONTINUATION	$406,250
														Subtotal = $406,250

Issue Date FY: 2018 ( Subtotal = $406,250 )
2018	2018	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	8	1/19/2018	NON-COMPETING CONTINUATION	$406,250
														Subtotal = $406,250

Issue Date FY: 2017 ( Subtotal = $406,250 )
2017	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	7	1/20/2017	NON-COMPETING CONTINUATION	$406,250
														Subtotal = $406,250

Issue Date FY: 2016 ( Subtotal = $406,250 )
2016	2016	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	6	1/18/2016	COMPETING CONTINUATION	$406,250
2016	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	5	1/18/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $406,250

Issue Date FY: 2014 ( Subtotal = $472,650 )
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	002	5	8/29/2014	SUPPLEMENT FOR EXPANSION	$32,242
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	5	7/29/2014	NON-COMPETING CONTINUATION	$381,650
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	5	8/20/2014	SUPPLEMENT FOR EXPANSION	$58,758
														Subtotal = $472,650

Issue Date FY: 2013 ( Subtotal = $359,532 )
2013	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	4	7/18/2013	NON-COMPETING CONTINUATION	$359,532
														Subtotal = $359,532

Issue Date FY: 2012 ( Subtotal = $383,277 )
2012	2012	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	3	7/9/2012	NON-COMPETING CONTINUATION	$383,277
														Subtotal = $383,277

Issue Date FY: 2011 ( Subtotal = $384,038 )
2011	2011	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	7/18/2011	NON-COMPETING CONTINUATION	$384,038
														Subtotal = $384,038

Issue Date FY: 2010 ( Subtotal = $388,654 )
2010	2010	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	1	7/20/2010	NEW	$0
2010	2010	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	1	6/10/2010	NEW	$388,654
														Subtotal = $388,654

Grand Total All Awards = $5,933,401

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Transcriptional Regulation of C. albicans Cell Fate and Host Interactions

Award Number: R01AI081704

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: 08/01/2010

PERIOD OF PERFORMANCE END DATE: 07/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer