Nickels Laboratory

Our lab studies transcription, the first step in gene expression, whereby the genetic information coded in the DNA is utilized for the synthesis of RNA.  Most regulation of gene expression occurs at the level of transcription.  Transcription in all cells is carried out by multisubunit RNA polymerases (RNAPs) that are conserved in sequence, structure and function from bacteria to humans.  Thus, a fundamental understanding of the diverse mechanisms employed by the bacterial cell to regulate RNAP function is important for understanding gene regulation in all organisms.  In addition, principles that emerge from investigations of the transcription apparatus and its regulation in bacterial systems permit development of new strategies to control microbial pathogens.

Transcription can be regulated during initiation, elongation, and termination by an enormous variety of regulatory factors that are either recruited to specific promoters or genes by sequences in the DNA or the RNA, or bound by RNAP in a manner that does not depend on any DNA or RNA sequence determinants.  We utilize state of the art high-throughput sequencing methods coupled with conventional genetic and biochemical approaches to gain a detailed mechanistic understanding of the processes underlying the regulation of gene expression at the level of transcription.  To facilitate our studies of transcription and its regulation we exploit the relative simplicity of the bacterial system.