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Mechanism and Regulation of Transcription Initiation

Award Number: R37GM051966
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/1995
PERIOD OF PERFORMANCE END DATE: 06/30/2017

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Mechanism and Regulation of Transcription Initiation - The goal of this research project is to understand the fundamental mechanisms by which single-subunit RNA polymerases catalyze transcription. Single-subunit RNA polymerases are widespread in nature transcribing not only the genomes of phages but also the genomes of mitochondria that are vital for energy production and survival of eukaryotes including humans. Understanding the molecular mechanisms of gene expression by single-subunit RNA polymerases has applications in developing therapeutics for numerous mitochondrial related human diseases as well as combating parasitic infections. It is recognized that transcription initiation, elongation, and termination all play essential roles in regulating gene expression. However, we lack quantitative description of these conserved transcriptional processes. By choosing enzymatically tractable systems, such as T7 RNA polymerase and mitochondrial RNA polymerase of the yeast, we are able to obtain in depth knowledge of each stage to ultimately develop a predictive and quantitative model of transcription. There is a need to develop new methods to assay the various steps of transcription initiation and elongation in real time that identify key intermediates and measure the rate constants and energetics of the elementary steps. One of our goals is to develop fluorescence-based transient state kinetic approaches that can be used in ensemble and single molecule experimental set up to measure the dynamics of transcription in real time. These methods will be developed through studies of T7 RNA polymerase and applied to understand the mechanism of mitochondrial RNA polymerases and associated factors. Unlike T7 RNA polymerase, the mitochondrial RNA polymerases require transcription factors, and one of our goals is to understand how these accessory factors aid in transcription and its regulation. The proposed studies will determine 1) the mechanism of polymerase translocation and fidelity of transcription elongation, 2) role ofthe transcription factors and accessory factors in various steps of transcription by the mitochondrial RNA polymerases, and 3) role of transcription in the initiation of replication.


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: 2017 ( Subtotal = $0 )
2017	2015	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	000	21	11/17/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $447,163 )
2015	2015	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	000	21	6/17/2015	NON-COMPETING CONTINUATION	$447,163
														Subtotal = $447,163

Issue Date FY: 2014 ( Subtotal = $446,755 )
2014	2014	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	002	20	6/19/2014	NON-COMPETING CONTINUATION	$447,163
2014	2013	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	001	19	2/10/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$11,055
2014	2012	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	18	2/7/2014	EXTENSION WITH OR WITHOUT FUNDS	$10,647
														Subtotal = $446,755

Issue Date FY: 2013 ( Subtotal = $240,347 )
2013	2013	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Biomedical Research and Research Training	002	19	2/10/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$11,055
2013	2013	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Biomedical Research and Research Training	000	19	8/15/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$431,512
2013	2012	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	001	18	8/20/2013	EXTENSION WITH OR WITHOUT FUNDS	-$180,110
														Subtotal = $240,347

Issue Date FY: 2012 ( Subtotal = $516,377 )
2012	2012	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	18	6/18/2012	EXTENSION WITH OR WITHOUT FUNDS	$516,377
														Subtotal = $516,377

Issue Date FY: 2011 ( Subtotal = $421,632 )
2011	2011	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	17	6/10/2011	NON-COMPETING CONTINUATION	$421,632
														Subtotal = $421,632

Issue Date FY: 2010 ( Subtotal = $425,955 )
2010	2010	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	16	5/28/2010	NON-COMPETING CONTINUATION	$425,955
														Subtotal = $425,955

Issue Date FY: 2009 ( Subtotal = $417,789 )
2009	2009	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	15	6/25/2009	NON-COMPETING CONTINUATION	$417,789
														Subtotal = $417,789

Issue Date FY: 2008 ( Subtotal = $405,685 )
2008	2008	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	14	7/22/2008	NON-COMPETING CONTINUATION	$405,685
														Subtotal = $405,685

Issue Date FY: 2007 ( Subtotal = $417,388 )
2007	2007	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	13	8/27/2007	COMPETING CONTINUATION	$417,388
														Subtotal = $417,388

Grand Total All Awards = $3,739,091

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Mechanism and Regulation of Transcription Initiation

Award Number: R37GM051966

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/1995

PERIOD OF PERFORMANCE END DATE: 06/30/2017

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