The virus structure programme aims to define the architecture of viral macromolecular assemblies and their interactions with host components. This cross-cutting research complements many of the research programmes across the CVR.
State of the art electron cryomicroscopy (cryoEM) combined with single-particle reconstruction (computational averaging of many thousands of particle images) offers the potential to characterise both viral and host components at close to atomic-resolution. Such data may then be interpreted to define protein tertiary structure and thereby identify key targets for intervention.
Lower-resolution analysis of unique entities such as enveloped viruses may be performed by cryotomography. Under certain circumstances, repeating identical features e.g. envelope glycoproteins, can be computationally extracted and averaged to enhance the resolution; a process termed sub-tomogram averaging.
The CVR virus structure group is well equipped to perform cryoEM and tomography of purified virus particles and related macromolecular assemblies. Furthermore we are highly focussed on imaging virus structures as they function in their natural environment through imaging of the virus-infected cell. In-situ structural biology is an exciting emerging field that we are fully engaged with and has the potential to deliver unique insights into virus behaviour.
Current research aims in this theme are:
- Defining the architecture and morphogenesis of influenza A virus (IAV),respiratory syncytial virus (RSV) and parainfluenza viruses (PIV)
- Building a detailed structural understanding of the feline calicivirus entry pathway
- Establishing cryoEM methods for three-dimensional imaging of viruses within the cell