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Interactions underlying resilient bacterial communities and successful colonization of host niches

Award Number: R35GM133775
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: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2030

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Interactions underlying resilient bacterial communities and successful colonization of host niches - Bacteria naturally inhabit different niches in the human host, such as the gut, and can opportunistically colonize sterile niches, such as tumors. Bacterial success in these complex environments depends on multiple factors that include the niche conditions and interactions with neighboring microorganisms. Our research leverages on genetically tractable model systems to study bacterial communities in vitro and bacterial colonization of host niches in vivo. We apply an interdisciplinary approach that combines functional genomics, computational analysis, and mathematical modeling to study these complex and dynamic systems. The first focus area is on investigating the factors that underly the complex spatial and temporal patterns observed in natural bacterial communities. Building on our previous work, we will use genetically engineered bacteria to implement mutualistic and competitive interactions and test how specific community properties emerge and change as a function of interaction parameters. Specifically, we will investigate how parameters of the community members dictate the spatial patterns that emerge when multi-member colonies form. We will also investigate the temporal patterns that form in cross-feeding communities and their capacity to support multi-member communities that are not exclusively co-dependent (often observed in nature). Addressing these questions in genetically tractable bacterial consortia will allow to disentangle some of the hidden rules that sustain complex microbial communities found in natural niches, such as the human gut. Resolving these rules will allow genetically engineering robust consortia for biotechnological and biomedical applications. Our second focus area is on bacterial colonization and adaptation to different host niches. Specifically, we will investigate bacterial colonization in an existing microbiome niche – the intestinal tract, and bacterial takeover of a sterile niche – solid cancer tumors. Work will use collections of thousands of bacterial mutants as well as collections of thousands equally fit wild-type E. coli clones tagged with DNA barcodes. Mutant collections allow inferring the bacterial pathways and processes needed for successful colonization while collections of equally fit clones allow inferring the dynamics of a bacterial population experiencing uniform selection. Measurements of bacterial load and clone (barcode) diversity in different colonization stages will be used to determine population bottlenecks, growth and death rates, and for evaluating alternative mathematical models of niche takeover. Our work will deepen the understanding of selection forces operating in the intestinal niche and will uncover, for the first time, the selection forces and population dynamics that govern bacterial infection of solid cancer tumors, an area in the field of tumor-microbiome research that is highly underexplored.


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: 2026 ( Subtotal = $460,625 )
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	7	2/10/2026	NON-COMPETING CONTINUATION	$460,625
														Subtotal = $460,625

Issue Date FY: 2025 ( Subtotal = $456,045 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	6	5/14/2025	COMPETING CONTINUATION	$460,625
2025	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	5	4/2/2025	NON-COMPETING CONTINUATION	-$4,580
														Subtotal = $456,045

Issue Date FY: 2023 ( Subtotal = $418,750 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	5	8/17/2023	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2022 ( Subtotal = $418,750 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	4	8/15/2022	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2021 ( Subtotal = $418,750 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	3	8/5/2021	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2020 ( Subtotal = $418,750 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	2	8/19/2020	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2019 ( Subtotal = $418,750 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	1	8/9/2019	NEW	$418,750
														Subtotal = $418,750

Grand Total All Awards = $3,010,420

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Interactions underlying resilient bacterial communities and successful colonization of host niches

Award Number: R35GM133775

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: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2030

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