Systematic identification and characterisation of poxvirus lateral body constituents using quantitative proteomics and advanced superresolution microscopy. (360G-Wellcome-106080_Z_14_Z)

The aim of this research program is to elucidate the molecular components of poxvirus lateral bodies and determine their role in the viral life cycle. Poxviruses are large, enveloped, double-stranded DNA viruses characterised by their complex structure and cytoplasmic replication site. All poxviruses, deposit two protein rich structures, termed lateral bodies, into the cell cytoplasm during infection. The development of poxviruses as vaccine vectors and oncolytic agents, as well as on-going zoon otic poxvirus outbreaks and the potential threat of smallpox bioterrorism, warrant continued research on these important pathogens. This study will focus on the prototypic poxvirus, vaccinia. Taking a novel interdisciplinary approach, I will use advanced technologies that allow for high-throughput mass spectrometry identification and then superresolution visualisation of lateral body constituents. This will be followed by characterisation of their roles in the viral life cycle and immunomodulati on using a variety of virology, cell biology, biochemistry, and microscopy technologies. This research will provide detailed understanding of how poxviruses use their lateral bodies to package and then deliver cell modulatory factors into the host cytosol during infection. This will elucidate the function of these poorly understood viral structures and may identify cell- or immune-modulating viral components with powerful potential therapeutic applications.