The proposed studies are part of our long-range effort to study the fundamental mechanisms of transcription and its regulation using bacterial model systems. Proper control of gene regulation is critical for organismal development, cellular response to environmental signals, and the prevention of disease states. The first step in gene expression, transcription, is carried out by multi-subunit RNA polymerases (RNAPs) that are conserved in sequence, structure and function from bacteria to humans. Thus, a detailed mechanistic understanding of transcription in bacteria facilitates an understanding of transcription in all organisms. The proposed studies will apply a comprehensive approach combining genetics, biochemistry, structural biology, genomic, and high- throughput sequencing based methods to (1) understand the diversity of regulatory mechanisms that link changes to cellular state to changes in the activity of RNAP and (2) obtain a quantitative understanding of transcription that defines the mechanistic basis for each step of transcription and confers the ability to predict transcriptional output from the DNA sequence content of a gene. We tackle these areas by developing new methodologies to understand the interface between DNA sequence and RNAP function, and to reexamine long-held notions of RNAP function for unexpected paradigms or unknown biology.

Public Health Relevance

Proper control of gene expression in all cells is critical for organismal development, cellular response to environmental signals, and the prevention of disease states. The proposed studies seek to obtain a detailed understanding of the mechanism and regulation of gene expression at the level of transcription. Thus, the proposed research may lead to discoveries with important implications for human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
3R35GM118059-02S1
Application #
9490833
Study Section
Program Officer
Sledjeski, Darren D
Project Start
2016-06-10
Project End
2021-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Rutgers University
Department
Type
Organized Research Units
DUNS #
001912864
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
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