Affiliations

Lab Director, Gralla Lab

Professor, Chemistry and Biochemistry, Biochemistry, Molecular Biology

Administrator, Chemistry and Biochemistry

Member, Graduate Program in Biochemistry, Molecular and Structural Biology, JCCC Gene Regulation Program Area, Molecular Biology Institute

Researcher, Biochemistry, Development and Gene Regulation

The overall goal is to define and understand critical protein-DNA and protein-protein interactions that occur during regulation of transcription and other processes that require the opening of duplex DNA. Emphasis is placed on merging genetic and biochemical information. Particular attention is paid to integration to identify unifying concepts in different organisms and systems. One current project involves the biochemistry of the multi-protein complex TFIIH. TFIIH is a master regulator of DNA transactions and is needed for control of DNA transcription and repair and for replication timing. Defects in TFIIH lead to several human diseases including cancer and premature aging. Most diseases track to one of the 2 helicases that are needed to open DNA during transcription or repair. Recent data point to a critical role of the XPB helicase in coupling transcription initiation to RNA processing and this is a primary focus of current attention. Another project involves studying the transcription responses induced by stresses encountered during bacterial pathogenesis. The emphasis is on identifying the components required and learning how they interact. This involves both protein and DNA components. The current focus is on learning how bacteria adapt to the weak acid and osmotic shocks encountered in the gut and the crowded population that typically precedes pathogenesis. Cross-comparisons of these 2 seemingly different systems are used to learn unifying principles and well as important differences.