Bridging the gap between cell and structural biology at the University of Leeds (360G-Wellcome-208395_Z_17_Z)

We request funds to purchase equipment to perform correlative light and electron microscopy (CLEM) and electron microscopy of cells & tissues at the University of Leeds. This will include: a high-pressure freezer to allow rapid freezing of large and/or labile specimens whilst minimizing structural deformation; a freeze-substitution unit for low-temperature substitution of water by dehydrating agents and fixatives, avoiding the damaging effects of room-temperature dehydration; a modern cryo-ultramicrotome, for room-temperature and cryo-sectioning of samples for (cryo-)EM imaging; and a cryo-CLEM system, to image cryo-fixed samples by fluorescent microscopy, identifying interesting biological events for further analysis at high-resolution by cryo-EM. This equipment will build upon the outstanding infrastructure for super-resolution light microscopy and cryo-EM in Leeds. The combination of new and existing equipment will give us an unprecedented ability to integrate high-resolution structural information into its cellular/tissue context. This will help us to tackle the most challenging projects in biomedical discovery, and understand the molecular basis of diseases such as infections, cardiovascular disease, neurodegeneration and cancer. We request £429k of Wellcome Trust funds, complementing the University’s contribution of ~£192k in capital and support salary costs, towards a total project cost of ~£621k.