Cryo-Electron Microscopy Research Infrastructure

The Oxford Centre for Particle Imaging at the Wellcome Trust Centre for Human Genetics is pivotal for pan-departmental access and training in biological electron cryo microscopy (cryoEM) and electron cryo tomography (cryoET) for the 300+ structural biology research community in Oxford. State-of-the-art cryoEM and cryoET can image the molecular mechanisms by which human cells, disease pathogens and vaccines work. Such studies can pinpoint how differences in the genetic makeup of individuals contribute to a wide range of medical conditions through effects at the cellular and molecular level. Likewise, the design of vaccines to combat emergent viruses can be guided by mapping the surface details of the virus that are best recognised by our immune system. This grant application is to upgrade instrumentation for state-of-the-art cryoEM and cryoET in OPIC. OPIC is
unique in Europe in having the capability, when necessary, to run cryoEM and cryoET data collection in containment. OPIC, through its association with the UK national facility, eBIC (electron Bio-Imaging Centre) at Diamond Light Source, provides access for such experiments to the broader national and international user community. On-going analyses on viruses and vaccines important to human health worldwide will benefit from the requested equipment.

The Oxford Centre for Particle Imaging (OPIC) at the Wellcome Trust Centre for Human Genetics (WTCHG) plays the leading role for biological cryo electron microscopy and tomography (cryoEM and cryoET) at Oxford University. OPIC also offers a unique capability of contained microscopy as part of eBIC, the national facility. The high-end cryoEM instrument in OPIC is a 12-year-old FEI F30
‘Polara’, which has become a bottleneck for our science due to its unreliability, low throughput and lack of ability to integrate latest technologies.
The requested Krios cryoEM will:
- Underpin the research of multiple groups within the WTCHG, that of the Structural Genomics Consortium (SGC) and other neighbouring biomedical researchers on the Old Road Campus.
- Serve as a lynch pin in the pan-departmental strategy for biological cryoEM across the University of Oxford.
- Provide access to high-end cryoEM and cryoET for eBIC users with projects requiring ACDP category 3 and DEFRA 4 levels of containment.
Research that will benefit includes:
- ‘structural vaccinology’ combining deep/single cell sequencing of the humoral response to emergent viruses with cryoEM mapping of epitopes.
- analyses of cell-cell signalling systems and virus-cell interactions using sub-tomogram averaging and whole cell cryoET combined with correlative light microscopy.