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Integrated transcriptomics and metabolomics approach to define pathogenicity of P.gingivalis

Award Number: R03DE028968
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: 07/30/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2023

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Integrated transcriptomics and metabolomics approach to define pathogenicity of P.gingivalis - Project abstract Porphyromonas gingivalis (Pg), a gram-negative asaccharolytic anaerobe, is a major causative pathogen of chronic periodontitis. Pg not only causes tooth loss, but is also associated with increased risk for other systemic diseases such as atherosclerosis. Endothelial cells provide an interface for the systemic dissemination of Pg. Pg evades endothelial cell defenses and persist within endothelial cells, thereby allowing chronic infections like periodontal disease and systemic diseases to develop. Pg persistence can also leads to endothelial dysfunction resulting in impaired inflammatory signals and atherosclerosis. Hence, it is critical to understand the mechanisms of Pg infection of endothelial cells. Our central hypothesis is that Pg invades endothelial cells and evades host defenses by regulating its gene expression and metabolic requirements to survive within endothelial cells. To test this hypothesis, we propose to employ an innovative approach of integrating transcriptomics and metabolomics to better understand the pathogenic nature of Pg and its interaction with the endothelial cells. This comprehensive approach of combining dual RNA-seq and metabolomics data will identify significant gene- metabolite integrated networks that are unique to Pg infection of endothelial cells. Consequently, these studies will define those metabolic changes that occur during intracellular adaptation and survival of Pg and provide much needed fundamental insights into periodontal disease and systemic diseases associated with Pg. In order to achieve this goal, we propose the following specific aims. Aim 1: To determine and compare the RNA expression patterns of P. gingivalis (W83, W83Δ0717 & W83Δ0717::0717) and host cells (HMVEC and HCAEC) during the invasion and persistence states. Aim 2: To define the metabolomic changes that occur during the invasion and persistence states of P. gingivalis (W83, W83Δ0717 & W83Δ0717::0717) in HMVEC and HCAEC cells. These studies will be the first to characterize the mRNA and metabolite patterns of both Pg and host cells during pathogenesis. The expected outcome of this work is a comprehensive understanding of what molecular mechanism(s) specific to gene-metabolite networks Pg utilizes during invasion and persistence states. The successful completion of the proposed studies will lay the groundwork for developing effective treatment strategies to prevent PD and its associated systemic diseases.


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 = -$273 )
2024	2021	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Oral Diseases and Disorders Research	000	3	6/10/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$273
														Subtotal = -$273

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	001	2	12/3/2021	NON-COMPETING CONTINUATION	-$8,851
2022	2021	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Oral Diseases and Disorders Research	002	3	12/3/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$79,196
2022	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	1	12/3/2021	NEW	-$70,345
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $155,041 )
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	2	2/17/2021	NON-COMPETING CONTINUATION	$152,500
2021	2021	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	001	2	8/3/2021	NON-COMPETING CONTINUATION	-$143,649
2021	2021	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Oral Diseases and Disorders Research	002	3	8/4/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$146,190
														Subtotal = $155,041

Issue Date FY: 2020 ( Subtotal = $152,500 )
2020	2020	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Oral Diseases and Disorders Research	000	1	2/21/2020	NEW	$152,500
														Subtotal = $152,500

Grand Total All Awards = $307,268

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Integrated transcriptomics and metabolomics approach to define pathogenicity of P.gingivalis

Award Number: R03DE028968

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: 07/30/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2023

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