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Spatial Organization of the Oral Microbiome

Award Number: R01DE022586
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/03/2012
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Spatial Organization of the Oral Microbiome - TITLE: Spatial Organization of the Oral Microbiome PI: Jessica Mark Welch Project Summary/Abstract Bacteria colonizing the human mouth play important roles not only in oral health, but in systemic health and disease. This proposal addresses the key unsolved question of how spatial organization of the oral microbiota is connected to its function at the micron scale. Our previous work pioneered the imaging of oral microbiome biogeography by developing a Combinatorial Labeling And Spectral Imaging - Fluorescence in situ Hybridization (CLASI-FISH) strategy to analyze the micron-scale architecture of microbial communities at a systems level. In this project we build on these findings to investigate structure-function relationships, assess complexity of consortia at micrometer scales within single human hosts, and develop multiplexed live cell imaging to study the dynamics of multispecies in vitro biofilms at the single-cell level. In Aim 1 we investigate how a key parameter of host-microbiome interaction, salivary nitrate concentration, affects the structure of the bacterial biofilm on the tongue dorsum. The nitrate-reducing capability of bacteria on the tongue plays a major role in the generation of nitric oxide, which impacts vasodilation and control of blood pressure. In turn, the secretion of nitrate into saliva by salivary glands affects the metabolism and composition of the tongue microbiota. Using dietary nitrate supplementation of volunteers, we will quantify the spatial organization of nitrate-metabolizing taxa in tongue biofilm consortia that developed in high and low salivary nitrate concentrations, and we will use whole-genome shotgun sequence data to determine which species and strains are responsive to nitrate. In Aim 2 we address an almost entirely unexplored question: in micron-scale neighborhoods in the oral microbiome, does each species function as a clone or as a complex mixture of strains? The answer to this question is important for learning to manipulate and modulate the oral microbiome and determining whether, for purposes such as microbiome transplants or building an in vitro biofilm model, a single strain is an adequate representative of the community. We will address this question by microdissection of single tongue dorsum consortia 100-200 micrometers in diameter, followed by whole-genome shotgun sequencing and analysis to assess whether natural oral consortia are made up of clones or complex populations. Live imaging is a powerful method of analysis of taxon-taxon interactions, but multiplexed live imaging of bacteria with single-cell resolution has been almost entirely absent from studies of the oral microbiome. The goal of Aim 3 is to develop a live-imaging system, using vital dyes, to differentiate up to 6 taxa within live simplified communities. We will use this system to investigate the dynamics of taxon-taxon interactions in consortia representing components of dental plaque and the tongue biofilm. Our goal is to learn how members of the oral microbiome respond to one another under controlled conditions, and to evaluate whether these in vitro systems develop spatial organization resembling those of natural communities.


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: 2024 ( Subtotal = $745,959 )
2024	2024	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	002	13	8/2/2024	NON-COMPETING CONTINUATION	$745,959
2024	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	12	11/7/2023	COMPETING CONTINUATION	$0
2024	2023	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	004	12	9/27/2024	COMPETING CONTINUATION	$162,823
2024	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	12	10/10/2023	COMPETING CONTINUATION	$0
2024	2022	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	003	11	9/27/2024	NON-COMPETING CONTINUATION	-$162,823
														Subtotal = $745,959

Issue Date FY: 2023 ( Subtotal = $779,978 )
2023	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	12	8/28/2023	COMPETING CONTINUATION	$779,978
2023	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	11	8/25/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $779,978

Issue Date FY: 2022 ( Subtotal = $615,059 )
2022	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	11	5/24/2022	NON-COMPETING CONTINUATION	$615,059
														Subtotal = $615,059

Issue Date FY: 2021 ( Subtotal = $621,272 )
2021	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	10	4/27/2021	NON-COMPETING CONTINUATION	$621,272
														Subtotal = $621,272

Issue Date FY: 2020 ( Subtotal = $621,272 )
2020	2020	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	9	5/12/2020	NON-COMPETING CONTINUATION	$621,272
														Subtotal = $621,272

Issue Date FY: 2019 ( Subtotal = $621,272 )
2019	2019	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	8	5/20/2019	NON-COMPETING CONTINUATION	$621,272
2019	2017	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	6	12/10/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $621,272

Issue Date FY: 2018 ( Subtotal = $651,316 )
2018	2018	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	7	6/22/2018	COMPETING CONTINUATION	$651,316
														Subtotal = $651,316

Issue Date FY: 2017 ( Subtotal = $490,691 )
2017	2017	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	6	5/23/2017	NON-COMPETING CONTINUATION	$49,070
2017	2017	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	6	11/8/2016	NON-COMPETING CONTINUATION	$441,621
														Subtotal = $490,691

Issue Date FY: 2016 ( Subtotal = $494,729 )
2016	2016	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	000	5	11/24/2015	NON-COMPETING CONTINUATION	$445,256
2016	2016	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	001	5	1/22/2016	NON-COMPETING CONTINUATION	$49,473
														Subtotal = $494,729

Issue Date FY: 2015 ( Subtotal = $504,561 )
2015	2015	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	001	4	12/31/2014	NON-COMPETING CONTINUATION	$50,457
2015	2015	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	000	4	11/17/2014	NON-COMPETING CONTINUATION	$454,104
														Subtotal = $504,561

Issue Date FY: 2014 ( Subtotal = $546,825 )
2014	2014	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	003	3	3/4/2014	NON-COMPETING CONTINUATION	$54,187
2014	2014	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	002	3	1/8/2014	NON-COMPETING CONTINUATION	$487,688
2014	2013	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	001	2	12/9/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$343,140
2014	2013	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Oral Diseases and Disorders Research	000	1	12/6/2013	NEW	-$338,190
														Subtotal = $546,825

Issue Date FY: 2013 ( Subtotal = $534,251 )
2013	2013	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Oral Diseases and Disorders Research	001	1	3/15/2013	NEW	$0
2013	2013	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Oral Diseases and Disorders Research	000	1	12/3/2012	NEW	$529,301
2013	2013	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	003	2	12/9/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$343,140
2013	2013	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Oral Diseases and Disorders Research	002	1	12/6/2013	NEW	-$338,190
														Subtotal = $534,251

Grand Total All Awards = $7,227,185

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Spatial Organization of the Oral Microbiome

Award Number: R01DE022586

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/03/2012

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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