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Molecular and pathogenic study of an oral TM7 strain, the first cultivated ultra-small bacterium

Award Number: R00DE027719
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: 01/13/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2023

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Molecular and pathogenic study of an oral TM7 strain, the first cultivated ultra-small bacterium - Project Summary/Abstract Increasing our knowledge of the human-associated as-yet-uncultivated bacteria is essential in understanding their potential role in human diseases. The TM7 phylum is one such group of bacteria. Despite its ubiquitous presence in the environment and in human body sites as well as its potential implication in periodontitis, no cultivable representatives of the TM7 phylum have been isolated until very recently. Furthermore, TM7 belongs to the newly described Candidate Phyla Radiation (CPR) bacteria, which comprise >15% (>35 phyla) of the entire bacterial domain and lack an isolated representative. Remarkably, CPR organisms share unique biology that does not exist in the rest of the bacterial domain, which include but not limited to ultra-small cell size (200-500nm) and reduced genome (<1Mb) that has highly restricted metabolic capabilities. Our lab isolated the first human oral TM7 species (TM7x) as an obligate epibiotic parasite that lives on the surface of its host bacterium XH001 (an oral Actinomyces odontolyticus strain). Using TM7x/XH001 as a model system, this proposal seeks to fulfill three fundamental knowledge gaps: (1) What are the specific molecular mechanisms that govern the interaction between TM7x and its host bacteria? (2) Do the same rules and mechanisms apply to all TM7 members? (3) What is the role of TM7 in human mucosal inflammatory diseases? The ultimate goal is to unravel the secret lifestyle of TM7 and other CPR bacteria, and truly grasp their impact on human diseases and the environment. Dr. Bor has spent his postdoctoral research studies characterizing the physiological and phenotypic behaviors of TM7x/XH001 interaction and therefore, mechanistic and pathogenic studies of the TM7 bacteria is a logical extension of his research. The proposed K99/R00 research is designed to supplement Dr. Bor's prior research experiences and to train him in required technical and intellectual skills to become an independent investigator. Dr. Bor will be trained at one of the leading research institutes, UCLA. His primary mentor, Dr. Shi, and co-mentors, Dr. He, Dr. McLean and Dr. Dewhirst are well-established, capable individuals who are dedicated to pushing the boundaries of dental research. After the mentored phase of this K99, Dr. Bor's career goal is to become a tenure-track faculty member at a leading academic research institute, where he can further develop his research program on CPR bacteria while mentoring and educating students. Dr. Bor's proposed work will provide key insights into the physiology and pathogenesis of this unique group of host-associated bacteria and may contribute to the development of novel therapeutic tools for treating periodontitis.


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 = $0 )
2024	2022	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	5	12/12/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $30,471 )
2023	2020	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	3	12/1/2022	EXTENSION WITH OR WITHOUT FUNDS	$30,471
														Subtotal = $30,471

Issue Date FY: 2022 ( Subtotal = $249,000 )
2022	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	5	11/23/2021	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2021 ( Subtotal = $249,000 )
2021	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	4	2/25/2021	NON-COMPETING CONTINUATION	$0
2021	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	4	11/25/2020	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2020 ( Subtotal = $249,000 )
2020	2020	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	3	1/13/2020	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $777,471

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Molecular and pathogenic study of an oral TM7 strain, the first cultivated ultra-small bacterium

Award Number: R00DE027719

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: 01/13/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2023

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