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Regulation of carbon utilization in gut-resident bacteria

Award Number: R35GM147512
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: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Regulation of carbon utilization in gut-resident bacteria - PROJECT SUMMARY The microbiota of the mammalian gut is a complex community of individual strains shaped in part by microbial competition over diet components. Despite computational analyses predicting enzymatic capacity of diverse bacteria, this knowledge is not sufficient to determine how diet influences bacterial abundance in the gut. In particular, little is known about regulation of carbon utilization enzymes in gut bacteria. Do they have mechanisms similar to E. coli carbon catabolite repression to consume preferred nutrients sequentially? Or do they consume all available nutrients simultaneously? How do these different strategies contribute to microbial abundance in the gut? We have identified a mechanism resembling carbon catabolite repression in Collinsella aerofaciens that may be a disadvantage when there is an abundance of secondary carbon source in the gut. Our laboratory seeks to characterize regulatory mechanisms governing carbon consumption in Collinsella species, in culture and in the mouse gut. Collinsella species are poorly studied Actinobacteria that are linked to chronic human diseases including type 2 diabetes and atherosclerosis. We have studied a group of closely related species and strains that vary in their regulation of carbon consumption. We will use this existing variability and experimental evolution to identify a common pathway of carbon catabolite repression in these bacteria. We will measure the heterogeneity of this pathway and related metabolic functions using single-cell RNA-seq. Finally, we will characterize the impact of this regulation on bacterial growth and competition in the mouse gut. Together, this research will define regulatory pathways that contribute to advantageous strategies in the complex nutrient environment of the mammalian intestine. Despite the vast number of correlative studies implicating a role for the gut microbiome in human disease, there remains much to explore in identifying bacterial metabolic pathways governing bacterial abundance and function in the gut. This gap limits both our understanding of the basic biology of these community interactions as well as the ability to design effective microbial therapeutics for human diseases characterized by complex microbial dysbiosis.


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 = $388,388 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	4	7/9/2025	NON-COMPETING CONTINUATION	$388,388
														Subtotal = $388,388

Issue Date FY: 2024 ( Subtotal = $875,345 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	002	3	7/2/2024	SUPPLEMENT FOR EXPANSION	$401,250
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	3	5/27/2024	NON-COMPETING CONTINUATION	$388,388
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	3	6/11/2024	SUPPLEMENT FOR EXPANSION	$85,707
														Subtotal = $875,345

Issue Date FY: 2023 ( Subtotal = $520,818 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	002	2	7/27/2023	SUPPLEMENT FOR EXPANSION	$46,723
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	2	6/13/2023	NON-COMPETING CONTINUATION	$388,388
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	2	7/26/2023	SUPPLEMENT FOR EXPANSION	$85,707
														Subtotal = $520,818

Issue Date FY: 2022 ( Subtotal = $376,348 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	1	8/12/2022	NEW	$376,348
														Subtotal = $376,348

Grand Total All Awards = $2,160,899

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Regulation of carbon utilization in gut-resident bacteria

Award Number: R35GM147512

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: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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