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Mechanisms and regulation of horizontal gene transfer by natural transformation in Vibrio cholerae

Award Number: R35GM128674
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The Dalia lab studies the regulation and mechanisms of horizontal gene transfer by natural transformation (NT) using Vibrio cholerae as a model system. While this bacterium is the causative agent of the diarrheal disease cholera, we do not seek to study bacterial pathogenesis. Instead, we leverage this well- established model system and the genetic tools we have developed to characterize NT in a physiologically relevant context. NT contributes to the rapid spread of antibiotic resistance determinants and virulence factors in bacterial pathogens. Thus, characterizing the regulation and mechanisms of NT may uncover novel approaches to combat diverse clinically relevant infections. The genes required for NT are tightly regulated, and only induced when V. cholerae forms biofilms on the chitinous shells of crustacean zooplankton in the aquatic environment. The formation of chitin biofilms is also important for the survival of this facultative pathogen in its environmental reservoir, and promotes the waterborne transmission of cholera. Vibrio-chitin interactions can be easily studied in a lab setting, which provides a physiologically relevant and highly tractable model system for studying NT. In the next five years, we will focus on three major areas. First, V. cholerae uses dynamic surface appendages called type IV pili to bind to chitinous surfaces and to take up DNA for NT. The mechanisms that regulate the dynamic extension and retraction of these appendages, however, remains poorly characterized. Using tools we helped develop to label type IV pili in live cells, we will address how motor ATPases, minor pilins, and other environmental cues regulate pilus dynamic activity. Second, we will study how two membrane-embedded DNA-binding transcription factors, ChiS and TfoS, coordinate to activate the chitin regulon in V. cholerae. Membrane- embedded regulators are understudied, and this work will help elucidate the dynamics and constraints for the DNA-binding activity of membrane-embedded vs soluble transcription factors. Third, we will use a combination of cell biological and genetic approaches to study horizontal gene transfer by natural transformation. Namely, we will address the spatiotemporal dynamics of natural transformation within chitin biofilms; and the impact of neighbor predation on these dynamics. Also, we will formally test the long-standing, yet untested, hypothesis that DNA uptake during natural transformation plays an important nutritional role. Together, our basic research extends a fundamental understanding of a number of critical and conserved processes (e.g. pili, signal transduction, horizontal gene transfer) that are shared by diverse microbial species, including many pathogens.


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 = $0 )
2025	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	7	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $468,179 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	7	5/27/2024	NON-COMPETING CONTINUATION	$468,179
														Subtotal = $468,179

Issue Date FY: 2023 ( Subtotal = $468,179 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	6	5/19/2023	COMPETING CONTINUATION	$468,179
														Subtotal = $468,179

Issue Date FY: 2022 ( Subtotal = $387,020 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	5	8/19/2022	NON-COMPETING CONTINUATION	$387,020
														Subtotal = $387,020

Issue Date FY: 2021 ( Subtotal = $387,020 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	4	8/12/2021	NON-COMPETING CONTINUATION	$387,020
														Subtotal = $387,020

Issue Date FY: 2020 ( Subtotal = $373,559 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	3	8/12/2020	NON-COMPETING CONTINUATION	$373,559
														Subtotal = $373,559

Issue Date FY: 2019 ( Subtotal = $373,559 )
2019	2019	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	2	8/12/2019	NON-COMPETING CONTINUATION	$373,559
														Subtotal = $373,559

Issue Date FY: 2018 ( Subtotal = $373,559 )
2018	2018	TRUSTEES OF INDIANA UNIVERSITY	BRYAN HALL 107 S INDIANA AVENUE	BLOOMINGTON	IN	47405	MONROE	USA	Biomedical Research and Research Training	000	1	8/24/2018	NEW	$373,559
														Subtotal = $373,559

Grand Total All Awards = $2,831,075

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Mechanisms and regulation of horizontal gene transfer by natural transformation in Vibrio cholerae

Award Number: R35GM128674

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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