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Mfd promotes mutagenesis and prevents protein damage in cells experiencing oxidative stress in Bacillus subtilis

Award Number: R15GM131410
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Summary This application explores the functions of a DNA repair factor as a new element affecting evolution and adaptation of bacteria, including those that cause infections. This is of scientific interest because it involves the discovery of molecular pathways that affect bacterial cell physiology and evolution in conditions of stress. Thus, the knowledge generated by this application has the potential to uncover novel targets for the treatment of pernicious bacterial infections. The hypothesis under study is that the Mfd factor, previously studied in the context of high-fidelity DNA repair of transcribed regions, mitigates the toxic effects associated with oxidative stress by mediating error-prone DNA repair of DNA lesions and activating expression of genes that prevent cell death. This hypothesis will be tested using genetic, biochemistry, and systems biology approaches. In Aim 1, we will test the concept that Mfd-dependent mutagenesis operates at genes that are highly transcribed in cells experiencing oxidative stress. This concept will be examined innovatively by measuring mutagenesis at the genomic level and in the absence of selection. Aim 2 will elucidate whether Mfd is important for activating expression of factors that protect against protein damage caused by oxidative stress independently of its previously associated DNA repair functions. In conclusion, the experiments in this application are straight-forward and self- contained and seek to determine new functions of the Mfd factor. Mfd is well-conserved in bacterial pathogens and so the research proposed can potentially uncover a novel therapeutic target.


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 = -$3,290 )
2024	2018	BOARD OF REGENTS OF NEVADA SYSTEM OF HIGHER EDUCATION	4505 S MARYLAND PKWY	LAS VEGAS	NV	89154	CLARK	USA	Biomedical Research and Research Training	000	1	10/1/2023	NEW	-$3,290
														Subtotal = -$3,290

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2018	BOARD OF REGENTS NEVADA SYSTEM OF HIGHER EDUCATION	4505 S MARYLAND PKWY	LAS VEGAS	NV	89154	CLARK	USA	Biomedical Research and Research Training	000	1	11/3/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $428,506 )
2018	2018	BOARD OF REGENTS NEVADA SYSTEM OF HIGHER EDUCATION	4505 S MARYLAND PKWY	LAS VEGAS	NV	89154	CLARK	USA	Biomedical Research and Research Training	000	1	9/19/2018	NEW	$428,506
														Subtotal = $428,506

Grand Total All Awards = $425,216

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Mfd promotes mutagenesis and prevents protein damage in cells experiencing oxidative stress in Bacillus subtilis

Award Number: R15GM131410

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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