Proper control of gene expression is essential for organismal development, cellular response to environmental signals, and the prevention of disease states. Transcription is the first step in gene expression and thus is highly regulated. Transcription in all cells is performed by multi-subunit RNA polymerases (RNAPs) that are conserved in sequence, structure and function from bacteria to humans. Our lab utilizes a range of approaches including molecular biology, genetics, biochemistry and high-throughput sequencing to obtain a detailed understanding of the mechanism and regulation of transcription. To facilitate our studies, we use bacterial RNAP as a model for understanding gene expression paradigms in all organisms.
Transcriptomes are dynamic and responsive to alterations in environmental conditions or growth state. According to the classical model, transcription is regulated primarily through the action of DNA-binding proteins that activate or repress transcription initiation, with a few long-studied exceptions. However, it is now abundantly apparent that cells employ a highly diverse range of mechanisms to control gene expression during all three phases of transcription: initiation, elongation and termination. An overarching goal of our studies is to understand the diversity of regulatory mechanisms that link changes to cellular state to changes in RNAP activity.