Structure and mechanism of nucleic acid-processing machines in viral biogenesis

The research will focus on analysing the structure and mechanism of nucleic acid machines involved in viral biogenesis. Although the main emphasis is on using structural approaches such as X-ray crystallography and Cryo-EM; we will also use complementary biophysical techniques including surface plasmon resonance, fluorescence-based activity/binding assays, analytical ultracentrifugation and SEC-MALLS, to define composition and stoichiometry of protein-nucleic acid complexes, in addition to the affinity of the interaction. Key goals: 1. To continue investigation into the mechanism of dsDNA packaging motors present in tailed bacteriophages and the closely related human herpes viruses. To obtain high-resolution asymmetric cryo-EM reconstructions of an active motor assembled from components derived from a themostable bacteriophage. 2. To understand the structure-function relationship in FtsK-like DNA packaging motors present in another large class of dsDNA viruses comprising bacterial tectiviruses and eukaryotic poxviruses. 3. To investigate the mechanism of RNA unwinding by 2C helicases present in enteroviruses (such as poliovirus) and to define the RNA-binding surface of the Zika Virus NS3 helicase. To perform pilot studies on exploiting this information for identifying lead compounds for the development of antivirals.