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Carbohydrate enzyme gene clusters in human gut microbiome

Award Number: R01GM140370
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: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Carbohydrate enzyme gene clusters in human gut microbiome - PROJECT SUMMARY Carbohydrate enzyme gene clusters in human gut microbiome Hippocrates said ~2,400 years ago: “Let food be thy medicine and medicine be thy food”. It is now well known that this is largely due to the “diet-microbiota-host” interactions that happen in the human gut. In particular, microbial degradation of carbohydrates can produce a variety of metabolites, which have a profound impact on human health. As a bioinformatics researcher in the Nebraska Food for Health Center, the long-term interests of the PI include: (i) develop specialized computational tools for better functional annotation of food-digesting microbial genomes and metagenomes, and (ii) characterize enzymes and other genetic elements that connect microbes, diets, and human health. The objective of this R01 project is to develop a suite of bioinformatics tools for functional annotation of carbohydrate active enzyme (CAZyme) and CAZyme gene clusters (CGCs) in human gut microbiome. The PI has over 10 years of experience in CAZyme bioinformatics tool development, and maintains a well-recognized CAZyme annotation database and web server called dbCAN (http://bcb.unl.edu/dbCAN2). This project aims to further dbCAN development to address fundamental personalized nutrition questions: (i) is a gut microbe able to utilize a specific type of glycan? (ii) can a person carrying certain gut microbes respond to an individualized diet (e.g., prebiotics: dietary compounds that are beneficial to human health)? To address these questions, new CAZyme annotation tools must have the ability to predict the carbohydrate substrates of CAZymes. Recent research has found that different CAZyme encoding genes are often co-localized with each other and with other genes (e.g., those encoding sugar transporters, regulators, and signaling proteins) in bacterial genomes to form CGCs (also known as polysaccharide utilization loci or PULs). Thus, the foundation of the new tool development is that the gene membership (or functional domain composition) of a CGC can be used to predict its carbohydrate substrates (e.g., xylans, pectins, glucans, etc.). The innovation is that machine learning approaches will be used to analyze a large number of experimentally characterized PULs curated from literature, and the extracted sequence features will be used to build effective classifiers to predict and classify CGCs in new genomes/metagenomes. The expected outcome will be novel and user-friendly open source computer programs, databases, and web servers that allow automated CGCs identification and substrate predictions. The significance is that the new tools will facilitate the experimental characterization of more PULs and their carbohydrate substrates in human gut microbiome (also in other carbohydrate rich environments). Therefore, this project will contribute computational solutions to the research of personalized nutrition, e.g., analyze a person's gut microbiome to predict if this person can respond to diets containing certain prebiotic glycans.


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 = $0 )
2025	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST # 830861	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	000	4	1/30/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $50,000 )
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	000	4	3/6/2024	NON-COMPETING CONTINUATION	$50,000
														Subtotal = $50,000

Issue Date FY: 2023 ( Subtotal = $521,436 )
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	002	3	9/1/2023	SUPPLEMENT FOR EXPANSION	$219,316
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	001	3	3/28/2023	NON-COMPETING CONTINUATION	$30,212
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	000	3	1/27/2023	NON-COMPETING CONTINUATION	$271,908
														Subtotal = $521,436

Issue Date FY: 2022 ( Subtotal = $584,619 )
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	002	2	8/3/2022	NON-COMPETING CONTINUATION	$30,212
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	000	2	2/8/2022	NON-COMPETING CONTINUATION	$271,908
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Trans-NIH Research Support	001	2	7/29/2022	SUPPLEMENT FOR EXPANSION	$282,499
														Subtotal = $584,619

Issue Date FY: 2021 ( Subtotal = $302,120 )
2021	2021	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Biomedical Research and Research Training	000	1	4/28/2021	NEW	$302,120
														Subtotal = $302,120

Grand Total All Awards = $1,458,175

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Carbohydrate enzyme gene clusters in human gut microbiome

Award Number: R01GM140370

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: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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