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Investigating the molecules and mechanisms of bacterial cell-cell interactions

Award Number: R35GM145261
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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Investigating the molecules and mechanisms of bacterial cell-cell interactions - PROJECT SUMMARY In nature, bacteria typically exist within multispecies communities. Bacterial communities play vital roles in shaping the environment and their plant and animals. In spite of the prevalence and importance of microbial communities, important gaps still remain in our understanding of how bacteria interact within these microbiomes. Our lab’s NIGMS-relevant research is focused on investigating the chemical, molecular, and genetic mechanisms bacteria use to chemically and physically interact within multispecies communities. We focus on the soil microbiome as our model system: the soil is not one of the most phylogenetically diverse microbial environments on the planet, but soil microbes are also the source of the majority of our antibiotics and many other therapeutics. Therefore, understanding the mechanisms bacteria use to interact within this natural environment will not only provide a systems-level understanding of complex natural microbiome interactions but also provide us with potential chemical tools and therapeutic leads to manipulate bacterial behavior. These bacterially generated compounds are celled specialized or secondary metabolites. These secreted chemical cues can act as cell-cell communication signals that influence the physiology and metabolism of neighboring bacteria. They play key roles in bacterial differentiation, or the development of transcriptionally distinct, heterogeneously expressed subpopulations of cells. We focus on the soil and probiotic bacterium Bacillus subtilis, which can differentiate into cells that are making biofilm matrix, swimming, or sporulating, among others. We are interested in understanding the transcriptional specificity, ancestral lineages, and spatial distributions of this cellular heterogeneity as well as what roles specialized metabolites play in its development. We also aim to discover specialized metabolites involved in interspecies cell-cell communication to expand our understanding of chemical interactions in native microbiomes and obtain chemical tools to modulate bacterial physiology. Finally, we seek to identify the genetic and molecular mechanisms these extracellular signals use to impact bacterial transcription, heterogeneity, and metabolic activity. This research is significant because it will reveal fundamental information about the chemical and genetic mechanisms bacteria use to interact with one another. Our results will deepen our molecular understanding of cell-cell interactions within microbial communities as well as enable the development of targeted interventions to manipulate microbial behavior in environmentally and therapeutically important bacteria.


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 = $431,170 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	002	4	7/24/2025	SUPPLEMENT FOR EXPANSION	$12,420
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	4	6/13/2025	NON-COMPETING CONTINUATION	$418,750
2025	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	3	11/8/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $431,170

Issue Date FY: 2024 ( Subtotal = $709,997 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	3	6/4/2024	NON-COMPETING CONTINUATION	$418,750
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	3	6/6/2024	SUPPLEMENT FOR EXPANSION	$74,516
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	002	3	7/10/2024	SUPPLEMENT FOR EXPANSION	$216,731
														Subtotal = $709,997

Issue Date FY: 2023 ( Subtotal = $535,108 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	1	5/23/2023	SUPPLEMENT FOR EXPANSION	$54,261
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	2	6/21/2023	NON-COMPETING CONTINUATION	$418,750
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	002	2	7/24/2023	SUPPLEMENT FOR EXPANSION	$62,097
														Subtotal = $535,108

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	1	8/18/2022	NEW	$418,750
														Subtotal = $418,750

Grand Total All Awards = $2,095,025

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Investigating the molecules and mechanisms of bacterial cell-cell interactions

Award Number: R35GM145261

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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