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Vibrio fischeri as a Model for Bacterial Colonization

Award Number: R37AI050661
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2001
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Vibrio fischeri as a Model for Bacterial Colonization - The long-term goals of the proposed research program are to provide insight into the complex dialogue that occurs each generation between humans and their microbiota during the critical period following birth. Recent research has indicated a strong correlation between outcomes of these early events and life-long health. However, the inaccessibility of colonized tissues and high diversity of the microbiota renders an in- depth study of early colonization of human tissues extremely challenging. When faced with such complex phenomena, biologists often turn to simpler model systems to provide insights into evolutionarily conserved features and reveal basic principles. To decipher the cellular and molecular mechanisms underlying the initiation of bacterial associations with apical surfaces of mucosal epithelia, the proposed program exploits the binary symbiosis between the bacterium Vibrio fischeri and its squid host, Euprymna scolopes. This relatively simple association has been studied for over two decades as a model for the chronic colonization of mucosa by Gram-negative bacteria. As in humans, the squid-vibrio association begins anew each generation, requiring a ‘winnowing’ of other environmental bacteria that results in persistent association restricted to the coevolved partners. In this system, the process of symbiosis initiation occurs across ~100 microns over minutes to hours. It can be directly imaged in its entirety using confocal microscopy, which offers the rare opportunity to define, with high temporal and spatial resolution, the reciprocal molecular and biochemical dialogue that results in the establishment of a specific, life-long beneficial symbiosis. This project brings together two collaborators, each with expertise in the biology of one of the symbiotic partners, and introduces new technology to the study of host-microbe interactions, including: HCR-FISH, which enables visualization of rare transcripts in host and symbiont cells; NanoString, a new technology for simultaneous analysis of dozens to hundreds of targeted transcripts; and high-efficiency RNAseq, which produces robust transcriptional libraries from as little as 10 ng total RNA (~105 bacteria). An understanding of the human microbiome is in its infancy, and this frontier field is currently at the stage of building paradigms. Within this context, as the squid-vibrio system has in the past, the results of the current study will shed light upon fundamental principles governing the onset of both beneficial and pathogenic associations. RELEVANCE (See instructions): During the colonization of humans and other animals, by either the normal microbiota or microbial pathogens, the first few hours are critical. The resulting interplay determines whether a healthy association will be fostered, a dysfunctional community will develop, or a frank pathogenesis will ensue. We will use innovative imaging, microbial genetics, and genomics/transcriptomics approaches to discover the molecular mechanisms underlying this crucial period, defining the general principles that govern the reciprocal interactions between host cells and their microbes.


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 = $698,745 )
2025	2025	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	000	23	2/13/2025	NON-COMPETING CONTINUATION	$698,745
														Subtotal = $698,745

Issue Date FY: 2024 ( Subtotal = $695,395 )
2024	2024	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	004	22	8/29/2024	NON-COMPETING CONTINUATION	$24,785
2024	2024	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	003	22	5/24/2024	NON-COMPETING CONTINUATION	$67,061
2024	2024	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	002	22	3/5/2024	NON-COMPETING CONTINUATION	$603,549
2024	2023	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	000	21	2/1/2024	EXTENSION WITH OR WITHOUT FUNDS	$244,017
2024	2023	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	005	21	8/30/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2022	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	001	20	2/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$244,017
														Subtotal = $695,395

Issue Date FY: 2023 ( Subtotal = $667,379 )
2023	2023	CARNEGIE INSTITUTION OF WASHINGTON	5241 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	000	21	3/6/2023	EXTENSION WITH OR WITHOUT FUNDS	$667,379
														Subtotal = $667,379

Issue Date FY: 2022 ( Subtotal = $578,010 )
2022	2022	CARNEGIE INSTITUTION OF WASHINGTON	5251 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	005	20	8/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$4
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	001	19	5/25/2022	NON-COMPETING CONTINUATION	-$506,334
2022	2022	CARNEGIE INSTITUTION OF WASHINGTON	5251 BROAD BRANCH RD NW	WASHINGTON	DC	20015	DISTRICT OF COLUMBIA	USA	Allergy and Infectious Diseases Research	002	20	5/25/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$578,009
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	004	19	8/29/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	000	19	1/19/2022	NON-COMPETING CONTINUATION	$506,335
2022	2021	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	003	18	8/29/2022	NON-COMPETING CONTINUATION	-$3
														Subtotal = $578,010

Issue Date FY: 2021 ( Subtotal = $512,703 )
2021	2021	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	000	18	2/2/2021	NON-COMPETING CONTINUATION	$512,703
														Subtotal = $512,703

Issue Date FY: 2020 ( Subtotal = $523,740 )
2020	2020	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	000	17	1/27/2020	NON-COMPETING CONTINUATION	$523,740
														Subtotal = $523,740

Issue Date FY: 2019 ( Subtotal = $518,221 )
2019	2019	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	000	16	1/18/2019	NON-COMPETING CONTINUATION	$518,221
														Subtotal = $518,221

Issue Date FY: 2018 ( Subtotal = $523,743 )
2018	2018	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	001	15	7/10/2018	COMPETING CONTINUATION	$3
2018	2018	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	000	15	2/7/2018	COMPETING CONTINUATION	$523,740
2018	2018	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Allergy and Infectious Diseases Research	002	15	9/5/2018	COMPETING CONTINUATION	$0
														Subtotal = $523,743

Grand Total All Awards = $4,717,936

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Vibrio fischeri as a Model for Bacterial Colonization

Award Number: R37AI050661

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2001

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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