RNA Polymerases and RNA-binding Proteins in Viral Infection and Mitochondrial Disease
Since its inception, the primary goal of this laboratory has been development of strategies to treat or to prevent infections by RNA viruses. We have used poliovirus and hepatitis C virus (HCV) as our primary model systems. Our expertise in virology, biochemistry and mechanistic enzymology brings a unique combination of intellectual and technical resources to the study of RNA viruses. Our initial focus was the viral RNA-dependent RNA polymerase (RdRp). In particular, we were interested in the kinetic, thermodynamic and structural basis for fidelity of nucleotide incorporation, a topic of considerable importance not only for accurate maintenance, transmission and expression of genetically encoded information but also for targeting the RdRp for antiviral therapy. These studies have led to exciting discoveries that have moved the lab into many new areas, including enzyme dynamics, vesicular trafficking, innate immunity, vaccine development and mitochondrial molecular biology. Our work is highly collaborative and includes research teams from academia (local, national and international), government and industry. We currently have projects in the following areas: RNA-dependent RNA polymerase mechanism, Viral attenuation and vaccine development, Picornavirus genome replication, Biochemical mechanisms and biological functions of HCV NS3 and NS5a proteins, Mitochondrial transcription and disease, and Lethal mutagenesis as an antiviral strategy.