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Host mechanisms of gut colonization by commensal bacteria that affect lifespan

Award Number: R01DK128454
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Host mechanisms of gut colonization by commensal bacteria that affect lifespan - Project Summary Gut bacteria associate with host tissues and alter host physiology, impacting lifespan and aging. Some types of bacteria, such as Lactobacilli, benefit health while others degrade it. A key gap in our knowledge is how the host constructs microenvironments that coordinate colonization by specific bacteria. In particular, which host cells (Aim 1), genes, and molecules (Aim 2) promote colonization by specific bacteria? As an important step forward, this proposal aims to investigate host mechanisms of bacterial colonization in Drosophila melanogaster using recently isolated bacterial strains of Lactobacillus plantarum and Acetobacter from a wild D. melanogaster, which are found to colonize a tightly-defined physical space in the fly gut. L. plantarum, is a probiotic in humans, and the fly provides unique and powerful genetic resources to study homologs of human disease genes. This proposal harnesses several unique assays developed to identify host mechanisms that mediate commensal strain specificity, including the host cell types, genes and molecules that recruit and maintain commensal bacteria. The central hypothesis is that specific cell types in the fly foregut produce a commensal niche : a specialized chemical and physical microenvironment that facilitates adhesion and proliferation of specific bacteria that may benefit the host. The proposal aims to (i) use single cell RNA sequencing to identify the specific host cell types and genes that create this specialized microenvironment. This will enable the use of Drosophila genetics to (ii) probe the mechanisms of host tissue maintainance through cell turnover and localized secretion of a defined extracellular matrix. As a critical test of the hypothesis, the proposal will examine the L. plantarum population kinetics that enable its association with the commensal niche. By studying commensal niche construction in the Drosophila gut, this research will establish a new paradigm that enables interrogation of the conserved molecular and cellular interactions between hosts and their commensals that influence host health. The proposal holds translational potential for developing tools to drive these beneficial interactions.


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: 2027 ( Subtotal = $0 )
2027	2024	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	10/14/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2026 ( Subtotal = $26,502 )
2026	2024	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/13/2026	NON-COMPETING CONTINUATION	-$328,403
2026	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	6/16/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$354,905
2026	2024	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	6/9/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $26,502

Issue Date FY: 2024 ( Subtotal = $387,672 )
2024	2024	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/29/2024	NON-COMPETING CONTINUATION	$387,672
														Subtotal = $387,672

Issue Date FY: 2023 ( Subtotal = $403,825 )
2023	2023	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/19/2023	NON-COMPETING CONTINUATION	$403,825
														Subtotal = $403,825

Issue Date FY: 2022 ( Subtotal = $403,825 )
2022	2022	CARNEGIE INSTITUTION OF WASHINGTON	5251 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/15/2022	NEW	$403,825
														Subtotal = $403,825

Grand Total All Awards = $1,221,824

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Host mechanisms of gut colonization by commensal bacteria that affect lifespan

Award Number: R01DK128454

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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