Cryo-electron tomography of respiratory syncytial virus morphogenesis in organotypic cell culture systems
Supervisors:
Prof David Bhella, School of Infection and Immunity (University of Glasgow)
Prof Ultan Power, School of Medicine, Dentistry and Biomedical Sciences and Wellcome-Wolfson Institute for Experimental Medicine (Queen's University Belfast)
Summary:
Respiratory syncytial virus (RSV) is a leading cause of paediatric respiratory disease, causing bronchiolitis in neonates and infants as well as severe respiratory illness in the elderly. This project aims to characterize the structure and assembly of RSV at the molecular level, using cryogenic electron tomography (CryoEM/ET). Three-dimensional image reconstruction will be applied to these data, to yield atomic models of protein-protein interactions driving virion morphogenesis. An important aspect of this project will be developing new approaches to imaging virus assembly in biologically relevant organoid culture systems. This will build an understanding of authentic virus particle assembly and how tissue ultrastructure may drive infectious processes. This project will build on expertise in well-differentiated paediatric airway epithelial cell culture systems at Queens University Belfast and cryoEM/ET for in situ structural biology at University of Glasgow. Furthermore, the project will benefit from access to the state-of-the-art cryo-EM facilities available at the Scottish Centre for Macromolecular Imaging (SCMI) and the vibrant community of structural biologists at University of Glasgow.