Thursday, July 31, 2025 7/31/2025

Chemical and biochemical tools to study the functions of exopolysaccharides in bacterial biofilms

Award Number: R35GM147110
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: 07/15/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Chemical and biochemical tools to study the functions of exopolysaccharides in bacterial biofilms - PROJECT SUMMARY/ABSTRACT: It is estimated that over 1.7 million hospital acquired infections per year in the U.S. result from microbial biofilms. New approaches to specifically target and disrupt bacterial biofilms will thus have a significant impact on human healthcare. Exopolysaccharides like poly-N-acetylglucosamine (PNAG) are critical biofilm components that facilitate cell-cell interactions and serve as a protective barrier against the host’s immune system and common antibiotic therapeutics used to treat bacterial infections. However, there is little is known about the molecular interactions of PNAG with other biofilm EPS components. Blocking the interactions between bacterial cells and PNAG or using glycosidase enzymes that break down PNAG and disrupt biofilms are attractive approaches to treat biofilm infections. Overall, our goal is to characterize molecular interaction networks of exopolysaccharides like PNAG, determine how they contribute to biofilm formation and dispersal, and develop novel strategies to treat biofilm infections by blocking these interaction networks or by catalyzing the breakdown of critical biofilm EPS components. To accomplish this overarching goal, we have identified two primary research areas for the next 5 years and plans for beyond. The first area seeks to develop tools for rapid identification of PNAG in bacterial biofilms and develop a live cell proximity labeling platform for identification and subsequent characterization of PNAG-binding proteins. These protein-carbohydrate binding interaction have the potential to be targets for new anti-biofilm therapeutics. A second area will develop high-throughput approaches to identify and subsequently engineer PNAG glycosidase enzymes through functional screening of environmental metagenomes and iterative site saturation mutagenesis approaches. To enable these studies, we have developed new colorimetric and fluorometric PNAG analogs that enable the high throughput identification of PNAG glycosidase activity. This research will establish a platform in my laboratory to rapidly identify and develop novel biocatalysts for biofilm dispersal activity. Overall, these research efforts will provide new unique insight into the role of PNAG in biofilm formation and will provide tools that will impact the way that we approach treating biofilm infections.


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 = $382,100 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	4	6/5/2025	NON-COMPETING CONTINUATION	$382,100
														Subtotal = $382,100

Issue Date FY: 2024 ( Subtotal = $619,966 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	3	6/4/2024	NON-COMPETING CONTINUATION	$382,100
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	3	6/11/2024	SUPPLEMENT FOR EXPANSION	$237,866
														Subtotal = $619,966

Issue Date FY: 2023 ( Subtotal = $382,100 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	2	5/30/2023	NON-COMPETING CONTINUATION	$382,100
														Subtotal = $382,100

Issue Date FY: 2022 ( Subtotal = $382,100 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	1	7/6/2022	NEW	$382,100
														Subtotal = $382,100

Grand Total All Awards = $1,766,266

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Chemical and biochemical tools to study the functions of exopolysaccharides in bacterial biofilms

Award Number: R35GM147110

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: 07/15/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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