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Functional Characterization of Essential Burkholderia pseudomallei Virulence Regulators

Award Number: R21AI123913
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: 03/10/2016
PERIOD OF PERFORMANCE END DATE: 02/28/2021

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Functional Characterization of Essential Burkholderia pseudomallei Virulence Regulators - DESCRIPTION (provided by applicant): Burkholderia pseudomallei (Bp), a facultative intracellular pathogen, is a tier 1 select agent due to its potential use as a bioweapon and the often fatal disease it causes, melioidosis. Melioidosis has a wide variety of symptoms that affects essentially every tissue of the body. The varieties in clinical manifestations is due to th fact that Bp is genetically diverse among species and has a wide array of virulence mechanisms used to establish disease In order to develop effective vaccines and treatment strategies, the molecular pathogenesis of Bp must be elucidated. To date, only a handful of pathogenesis mechanisms have been described, for a bacterium with a very large and diverse genome of >7 mega base pairs. Through our innovative approach of transcriptionally profiling single Bp cells at different stages of infection, we have identified four hypothetical regulators essential for complete Bp pathogenesis in vivo. To study the pathogenic processes and the genes controlled by these regulators we propose Aim 1, which will identify the regulation networks and characterize their roles in pathogenesis. This will shed light on the regulation of either known virulence pathways and/or novel virulence pathways adding to the complete understanding of the Bp intracellular lifecycle. Aim 2 proposes the mechanistic characterization of these novel transcriptional regulators by determining DNA- regulator interactions across the entire genome. This analysis will allow for identification of binding motifs for each regulator and validate their function. Taken together, the proposed aims will greatly enrich the understanding of Bp infection within the host that can lead to the development of novel vaccine and therapeutic strategies. The overall methodology used in this proposal has broad applicability to study other medically significant facultative intracellular 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: 2021 ( Subtotal = $0 )
2021	2017	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Microbiology and Infectious Diseases Research	000	2	9/2/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2017	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Microbiology and Infectious Diseases Research	000	2	3/5/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Microbiology and Infectious Diseases Research	000	2	3/7/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $176,875 )
2017	2017	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Microbiology and Infectious Diseases Research	000	2	2/21/2017	NON-COMPETING CONTINUATION	$176,875
														Subtotal = $176,875

Issue Date FY: 2016 ( Subtotal = $212,250 )
2016	2016	UNIVERSITY OF HAWAII	2530 Dole St., Sakamaki D200	HONOLULU	HI	96822	HONOLULU	USA	Microbiology and Infectious Diseases Research	000	1	3/7/2016	NEW	$212,250
														Subtotal = $212,250

Grand Total All Awards = $389,125

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Functional Characterization of Essential Burkholderia pseudomallei Virulence Regulators

Award Number: R21AI123913

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: 03/10/2016

PERIOD OF PERFORMANCE END DATE: 02/28/2021

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