Our research focuses on RNA polymerase, the central enzyme of gene expression in all free-living organisms. Our goal is to understand how RNA polymerase is regulated during the process of transcription (RNA synthesis). In organisms from bacteria to humans, the cell's ability to make long RNA chains, which include most mRNAs and some structural RNAs (e.g., rRNA), requires that extrinsic elongation regulators interact with RNA polymerase to suppress its innate tendency to fall into inactive off-line states that include long pauses, arrest, or termination. We seek to understand the fundamental properties of RNA polymerase that make it susceptible to pausing, arrest, or termination and how elongation regulators alter these properties. We study RNA polymerases from both bacterial and human cells and use a variety of approaches, from genetics to biophysics to structural biology, to study this fundamental paradigm of gene regulation. Lab members are engaged in experiments ranging from detailed biochemical characterization of protein-nucleic acid interactions, to the study of transcription regulators in cells using microarray methods (so-called ChIP chip), to collaborative projects with other labs to study transcription by single molecules of RNA polymerase and to obtain crystallographic sturctures of RNA polymerase and transcription regulators. Our work has practical applications in drug discovery by identification on novel RNA polymerase inhibitors and in controlling transcriptional programs for synthetic microbiology.
The lab also is initiating collaborative projects using microbial synthetic biology to produce new microbes for bioenergy applications as part of the Great Lakes Bioenergy Research Center. That effort is just getting off the ground in Madison. Stay tuned for more developments.