Molecular biology of RNA picornaviruses; protein translation, proteolytic
processing; RNA replication; viral pathogenesis; viral vaccines; bioinformatics;
comparative proteomics, sequence analysis; computer-assisted RNA structure determinations.
We are interested in
all aspects of RNA virology and in bioinformatics methods for viral genomics. Among major laboratory goals are
to explore and define the relationship of the cardiovirus genus to
other members of the picornavirus family and to exploit the unique
features of the cardioviruses to examine molecular questions about
picornavirus translation, proteolytic processing, morphogenesis and
pathogenicity. We have developed extraordinarily powerful experimental systems
for examining IRES-dependent viral protein expression, RNA synthesis, virion assembly and virus-host interactions. We use high-tec recombinant engineering, reverse genetics, biochemistry, cell-free protein synthesis techniques, cell imaging and applied immunology to unravel the virus life cycle, step by step. Current projects include:
1) investigating the roles of RNA form and function in the non-coding sequences of viruses; 2) the mechanism of viral RNA replication; 3) investigation of "toxic ribosome" synthesis and host translational shutoff by viruses; 4) the nuclear life cycle of cytoplasmic viruses; 5) role of viral proteins in the disruption of RanGTPase-dependent nucleocytoplasmic protein and RNA cycling; 6) the proteases of rhinoviruses and their role in shutoff of host cell functions; 7) development and implementation of new techniques in bioinformatics, sequence analysis, comparative genome evolution, and advanced computer methods for RNA folding and molecular genomics.
Additionally, many of
our genetically engineered viruses have proven to be superb attenuated
vaccines or vaccine vectors, in that they provide effective, long-lived
anti-picornavirus immunity in many species of mammals, including primates.
We are exploiting these constructions for the prevention of picornavirus diseases, but have also harnessed these agents into novel, recombinant vaccine vectors. Therefore, another major research direction is the characterization of the molecular basis for viral attenuation in these cardioviruses with the nobjective of exploiting this phenomena and the principles
to be learned from it, for the development of new and effective vaccine
Typically: 2 scientists,
2-4 postdocs, 2-4 grad students, 2 undergrads, 2 hourlies, 1 specialist
and 2 hamsters.