Accelerating throughput at Scotland's national Cryo-EM centre - a next generation direct electron detector for SCMI.

Structural biologists strive to understand the shape of biological molecules, the 'machinery of life', at the atomic level. In 1953, Watson and Crick published the most famous structure of a biological molecule - that of DNA. In each of our cells, our entire genome, the information that tells our bodies how to make and maintain us, is written in to this elegant double-helix structure, using an alphabet of only four letters. The interpretation of our genome, by our cells, leads to the production of a vast array of protein molecules. These are much more complex structures, and are the machines for which our DNA is the blue-print. To understand biological processes, such as how a virus can enter our bodies and cause disease, requires us to work to understand the shapes of protein molecules. In the case of a virus, such as the coronavirus that caused a pandemic and changed our lives so dramatically these past few years, we wish to understand the structures of the proteins that the virus is made of, and how they interact with our own proteins to cause disease. To do this, we purify the proteins, freeze them, and image them in a very powerful microscope. This process is called cryogenic electron microscopy, or more commonly 'cryo-EM'. Images from cryo-EM can be processed in computers, to calculate the shapes of the protein molecule of interest at high resolution. This allow us to build a model of the protein in which we can confidently define the position of individual atoms. In the MRC - University of Glasgow Centre for Virus Research (CVR), we perform cryo-EM experiments using the facilities available at the Scottish Centre for Macromolecular Imaging (SCMI), which is located in our building. This centre was established in 2018 and is one of only a handful of high-performance cryo-EM centres in the United Kingdom, and the only one in Scotland. We wish to build the capacity of the SCMI to solve protein structures faster, and to higher resolution, by the addition of a state-of-the-art camera system. This will dramatically speed up our experiments, allowing researchers to collect enough cryo-EM images to solve their protein structures in four to five hours, rather than the two to three days currently required. Cryo-EM equipment is very expensive to run - one day of microscope time costs more than £1,000. This investment will greatly improve the efficiency of our science and the quality of structures we are able to solve.