Structural biology and imaging platform

High-resolution imaging technologies are powerful tools to help us understand how viruses cause disease. The structural biology and imaging platform provides access to state-of-the-art tools to allow visualisation of viral processes, supported by expert technologists. The platform supports the investigation of virus behaviour across scales ranging from resolving the atomic structure of the molecules that virus particles (virions) are made up of and how they interact with those of the infected host, through to imaging viruses in infected tissues.
These tools will be used by investigators in the CVR to understand e.g., how viruses can attach to and enter host cells, and how the molecules that perform this vital function evolve to avoid the host immune response; how cells can respond to the presence of a virus by for example making special structures to wrap up the viral genome and stop it expressing, or shutting down host processes that the virus needs to replicate; how populations of viruses can interact with each other as they move through an organ such as the lung; and how viruses assemble and leave an infected cell.

The Structural Biology and Imaging platform provides access to high-performance light and electron imaging capabilities for the study of virus biology spanning length-scales from near-atomic resolution macromolecular structure determination through to three-dimensional (3D) imaging of tissues and organotypic cell-culture systems. The platform also provides access to computational resources for image processing and data analysis. The platform includes access to the Scottish Centre for Macromolecular Imaging (SCMI) – Scotland’s national centre for cryogenic electron microscopy, which is housed within the CVR. SCMI’s frontline instrument is a state-of-the-art automated 300 keV cryo-EM: the JEOL CryoARM 300. To support project development SCMI offers users two further instruments: a JEOL 1400 120 keV cryoTEM and a JEOL F2 200 keV cryoTEM for screening and preliminary data acquisition.
The CryoARM platform is a newly developed instrument and a unique feature of SCMI among UK cryo-EM centres and among the first three installations worldwide. SCMI has therefore taken a global leadership role in supporting the manufacturer to deliver cutting-edge capabilities to the user community. SCMI provides supported access to cryo-EM for single-particle structure analysis at sufficient resolution to support the construction of atomic models of macromolecular assemblies; electron tomography for the analysis of unique assemblies in situ; microcrystal electron diffraction; cryogenic scanning transmission electron microscopy and correlated light and electron microscopy.
Light microscopy capabilities offered by the platform include super-resolution (PALM, dSTORM, AiryScan) for high-resolution localisation of viral and host proteins, and single-molecule Förster resonance energy transfer (smFRET) for measuring protein dynamics. High-content imaging capabilities include automated slide-scanning for high-throughput imaging of thin-sectioned tissue; an imaging cytometer for imaging adherent and suspension cell-cultures in microwell plates, and a highly multiplexed fluorescence imaging system. Tissue and organoid imaging is also available using confocal and lightsheet microscopy, allowing 3D fluorescence microscopy of ex vivo tissues, organotypic cell cultures and small organisms such as mosquitos and ticks.
Together the platform provides access to a powerful array of imaging technologies supporting research programmes investigating virus biology from macromolecular structure, cell and tissue biology through to within host spread of infection.