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Bacterial quorum sensing

Award Number: R35GM136218
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: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Bacterial quorum sensing - PROJECT SUMMARY Quorum sensing (QS) is a form of cell-cell communication that allows members of a population to coordinate cooperative activities in a cell density-dependent fashion. I am interested in bacterial QS control of cooperative activities at a chemical, cellular and molecular level for three reasons. (I) Bacteria such as our main model, Pseudomonas aeruginosa are ideal for studies of basic biological principles that underlie sociality. (II) It has become clear that if we seek to understand bacterial communities, social interactions must be considered. (III) There is an idea that QS and QS control of social activities in bacteria can serve as anti-bacterial virulence therapeutic targets. I specifically focus on the acyl-homoserine lactone-LuxI-type signal generator/LuxR-type signal responsive transcription factor pairs. My interests revolve around basic QS mechanisms, the selective pressures favoring QS control of gene expression, and the costs and benefits of QS in bacteria. It is clear that cooperativity is an evolved biological phenomenon, but there is considerable controversy about the selective forces allowing stable cooperativity. What are the costs and benefits of cooperativity, and what are the possible advantages to controlling cooperativity by QS? In the past ten years we have made enormous advances in understanding at a molecular level how cooperation is stabilized in P. aeruginosa and how we can destabilize it. These advances are important to the field of population biology and to our understanding of the roles P. aeruginosa QS plays in certain infections. Our continued research will use molecular genetic approaches to investigate QS control of gene expression, and we will continue to introduce new techniques and concepts into what has become a vibrant field of microbiological research. I believe we are now in position to address fundamental questions about evolution of QS signal diversity by continued studies of pure cultures of P. aeruginosa. We also plan to expand our efforts to consider species-specific QS in polymicrobial communities by developing an understanding of acyl-homoserine lactone QS in the context of the human intestinal microbiome. Our research is fundamental to efforts aimed at manipulating QS during infections or in complex microbial communities, and for biotechnological applications. We aim to better understand the role of QS during human infections and as it relates to microbiome activity in human health and disease. My long-term vision is: I. To understand how the diversity of QS systems has evolved, II. To attain a conceptual framework to explain how communication and cooperative activities are wired to provide stability of bacterial group activities and how we might be able to use the knowledge to manipulate bacterial populations. III. To gain insights about intraspecific cooperation in the context of a complex multispecies microbial community.


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 = $427,625 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	7	4/6/2026	NON-COMPETING CONTINUATION	$427,625
														Subtotal = $427,625

Issue Date FY: 2025 ( Subtotal = $427,625 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	6	5/11/2025	COMPETING CONTINUATION	$427,625
2025	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	5	11/11/2024	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	002	5	6/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $427,625

Issue Date FY: 2024 ( Subtotal = $388,750 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	5	6/24/2024	NON-COMPETING CONTINUATION	$38,874
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	5	3/27/2024	NON-COMPETING CONTINUATION	$349,876
														Subtotal = $388,750

Issue Date FY: 2023 ( Subtotal = $445,716 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	4	3/29/2023	NON-COMPETING CONTINUATION	$388,750
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	4	7/28/2023	SUPPLEMENT FOR EXPANSION	$56,966
														Subtotal = $445,716

Issue Date FY: 2022 ( Subtotal = $388,750 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	3	3/10/2022	NON-COMPETING CONTINUATION	$349,871
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	3	6/23/2022	NON-COMPETING CONTINUATION	$38,879
														Subtotal = $388,750

Issue Date FY: 2021 ( Subtotal = $388,750 )
2021	2021	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	2	3/11/2021	NON-COMPETING CONTINUATION	$388,750
														Subtotal = $388,750

Issue Date FY: 2020 ( Subtotal = $388,750 )
2020	2020	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	1	3/26/2020	NEW	$388,750
														Subtotal = $388,750

Grand Total All Awards = $2,855,966

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Bacterial quorum sensing

Award Number: R35GM136218

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: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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