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Distinguishing features of C. albicans pseudouridylation and their roles in pathogenesis

Award Number: R15AI130950
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: 02/06/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Distinguishing features of C. albicans pseudouridylation and their roles in pathogenesis - Project Summary: The proposed research leverages recent technological breakthroughs to investigate aspects of pseudouridylation and pseudouridine degradation that distinguish C. albicans from humans. Increased resistance to the few treatment options available for C. albicans infection underscores the importance of understanding how fungal pathogens differ from humans at the molecular level. The proposed research addresses fundamental questions about C. albicans biology by investigating essential aspects of RNA metabolism and has the potential to identify novel antifungal targets. The long-term objective of the proposed research is to understand how RNA modification and processing differ between humans and pathogenic fungi. Pseudouridine is an RNA modification found in a wide variety of RNA molecules in all kingdoms of life. Although pseudouridine is widespread, the amount and mechanism by which pseudouridylation occurs varies tremendously between taxa. Preliminary data indicate C. albicans Pus7 is critical for biofilm formation and rRNA processing. The mechanisms by which Pus7 absence leads to these phenotypes has not been investigated. Undergraduate and masters students will identify Pus7 substrates and determine where it localizes in the cell. The data collected will begin to develop a model for Pus7’s role in vivo. When RNA is degraded, the pseudouridine C-C glycosidic bond is degraded by pseudouridine glycosidases and kinases. While highly conserved in bacteria and most fungi these enzymes are not present in mammals or members of the Saccharomyces fungal clade. Little is known about this family of enzymes and the experiments proposed will be the first characterization of these enzymes in fungi. Undergraduate and masters students in the Bernstein lab will knockout these enzymes and determine how this effects C. albicans phenotype. Students will examine how pseudouridine glycosidase and kinase transcription is regulated. C-C glycosidic bond cleavage is an enzymatic activity not found in mammalian cells, and as such could be an important therapeutic target. Answering these questions will demand students perform medically relevant experiments in an important human fungal pathogen. Students in the Bernstein lab will gain experience in a wide variety of fundamental molecular biology techniques including cutting-edge CRISPR genome-editing technology. Students will be directly supervised by Dr. Bernstein and will participate in experimental design, data collection, interpretation, and dissemination of results. Furthermore, portions of the experiments proposed will be incorporated into the laboratory components of two courses taught by Dr. Bernstein, exposing an additional 32 students to significant biomedical research every year. Undergraduate and masters students in the Bernstein laboratory and both classes will be positioned to make discoveries that have a direct impact on our understanding of fungal pathogenesis and human health. These experiences serve them well as they pursue careers and further education after graduation.


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 = $0 )
2024	2021	BALL STATE UNIVERSITY	2000 W UNIVERSITY AVE	MUNCIE	IN	47306	DELAWARE	USA	Allergy and Infectious Diseases Research	000	2	4/11/2024	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	BALL STATE UNIVERSITY	2000 UNIVERSITY AVE	MUNCIE	IN	47306	DELAWARE	USA	Allergy and Infectious Diseases Research	001	2	5/5/2022	COMPETING CONTINUATION	$52,609
2022	2017	BALL STATE UNIVERSITY	2000 UNIVERSITY AVE	MUNCIE	IN	47306	DELAWARE	USA	Allergy and Infectious Diseases Research	000	1	5/5/2022	NEW	-$52,609
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $433,183 )
2021	2021	BALL STATE UNIVERSITY	2000 UNIVERSITY AVE	MUNCIE	IN	47306	DELAWARE	USA	Allergy and Infectious Diseases Research	002	2	5/13/2021	COMPETING CONTINUATION	$433,183
2021	2017	BALL STATE UNIVERSITY	2000 UNIVERSITY AVE	MUNCIE	IN	47306	DELAWARE	USA	Allergy and Infectious Diseases Research	001	1	5/4/2021	NEW	$0
2021	2017	BALL STATE UNIVERSITY	2000 UNIVERSITY AVE	MUNCIE	IN	47306	DELAWARE	USA	Allergy and Infectious Diseases Research	000	1	2/23/2021	NEW	$0
														Subtotal = $433,183

Issue Date FY: 2017 ( Subtotal = $441,234 )
2017	2017	BALL STATE UNIVERSITY	2000 UNIVERSITY AVE	MUNCIE	IN	47306	DELAWARE	USA	Allergy and Infectious Diseases Research	000	1	2/6/2017	NEW	$441,234
														Subtotal = $441,234

Grand Total All Awards = $874,417

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Distinguishing features of C. albicans pseudouridylation and their roles in pathogenesis

Award Number: R15AI130950

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: 02/06/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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