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 multi-subunit 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. Furthermore, because of its simpler composition and the highly developed genetic tools available in bacteria, the bacterial RNAP provides a powerful model system for detailed mechanistic studies. The principles that emerge from studies of the fundamental mechanisms of transcription and its regulation in the bacterial system shed mechanistic insight into transcription based processes that underlie human development and human disease processes such as cancer.