Structure/Dynamics/Function Correlations in the Cystoviral Polymerase Complex

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Many viruses contain RNA genomes and utilize a multi-protein polymerase complex (PX) for RNA replication and transcription, processes that are central to viral infectivity, survival and propagation. In bacteriophages of the family cystoviridae (cystoviruses) that contain a double stranded RNA (dsRNA) genome, the PX is a four-protein complex that includes an RNA-directed RNA polymerase (P2) that replicates and transcribes viral RNA (vRNA) in concert with proteins P1, P4 and P7. A complete understanding of the functional interactions of the PX proteins in spatial and temporal terms at atomic or near-atomic resolution is important not only in the context of cystoviruses in particular but for dsRNA viruses in general. The present project will focus on elucidating structure/function/dynamics correlations involving two of these PX proteins, the polymerase P2 that forms the central machinery of the PX, performing the transcription and replication functions, and the essential protein P7 that regulates genome packaging and helps in maintaining transcriptional fidelity.The City College of New York (CCNY), a primarily minority serving institution, has registered a significant drop in the number of African-American students enrolling in undergraduate degree programs over the last decade. The level of enrollment of Hispanic students has also not kept up with a corresponding population increase in the five boroughs of New York City over the same period. The PI intends to raise the level of enrollment, retention and graduation of these minority populations in the science disciplines at CCNY using a three-tier approach: (1) Enrollment: specifically targeting high-schools specializing in the sciences in upper Manhattan and the Bronx with predominantly minority students, through teacher training and by research mentoring of a small number of promising students in the PI's laboratory; (2) Retention: active mentoring of pre-science majors through the City College Academy for Professional Preparation (CCAPP); and (3) Undergraduate research: involving undergraduate students in specific parts of the research project, providing them an experience rather unique in the City University of New York system of incorporating two cutting edge biophysical techniques NMR and X-Ray crystallography in a complementary fashion to elucidate the structural and dynamic determinants of biomolecular function.