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MICROSCOPY & IMAGING


included mapping the Foot and Mouth Virus disease structure, discovering the first structure of an enveloped virus, and advancing our understanding of viral assembly, replication, and infection. Known for pushing technological developments that drive innovative science forward, Stuart was a key player in the case for funding Diamond and eBIC. Te technical developments made at


synchrotrons have enabled the process of getting structural information on the therapeutic targets and on the complex of a drug with its target to be speeded


take it through an analysis pipeline, often to a result, without any intervention. Stuart says: “It takes a long time to set that up – years of work – but once you achieve it then you can open up methods to a much broader community. And the same is starting to be true for electron microscopy. It’s at an earlier stage, the methods are still changing quite rapidly, but one of the challenges that people in Diamond and elsewhere are trying to address is: can we make pipelines so that people can come with a sample, and very quickly get some sort of feedback on the


EBIC AND CRYO-EM AT DIAMOND C


ryo-electron microscopy, or cryo-EM, is one of science’s most advanced techniques and


has become an essential tool for the biological sciences. Operated under very cold conditions (at -200°C using liquid nitrogen), it is helping to uncover even more about the minute, hidden elements in matter, leading to advancements in medicine, bio-engineering, and our fundamental understanding of the world around us. Its ability to quickly and simply illuminate large and complex components makes it a profoundly useful addition to the arsenal of techniques that scientists use to explore the molecular and atomic world and generate advances. Using cryo- EM, researchers can now capture freeze-frame images of dynamic biomolecules at high resolution. This technology has taken biochemistry into a new era. Better microscopes, electron detectors and computer programmes are pushing the technique further. This rapid progress is having a direct impact on drug discovery and medical treatments At Diamond, scientists can


access state-of-the-art cryo-EM facilities through the Electron Bio- Imaging Centre (eBIC), for both single particle analysis and cryo-


60 www.scientistlive.com


tomography and onsite cryo-electron microscopes are currently being used by scientists to study everything, from complex virus structures, to never before seen proteins. eBIC was


Diamond Light Source, the UK’s national synchrotron


established at Diamond Light Source following the award of a £15.6 million grant from the Wellcome Trust, the Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC). It was the first high-end cryo-electron microscopy (cryo-EM) facility worldwide to be embedded in a synchrotron and user operations have been set up to mirror the well-established synchrotron beamline model. eBIC is a collaboration between Diamond, Birkbeck College and Oxford University. With its advanced microscopes, detectors and software, eBIC allows scientists to investigate and visualise the structure of individual cells and bio- molecules. eBIC has rapidly developed since


it welcomed the first user group in July 2015. A key aim of the centre, enabled by the synchrotron access model, was to provide a state-of-


the-art-facility for single particle cryo-EM and cryo-ET through cost- effective, peer-reviewed access based on scientific excellence. The swift provision of high-end microscopes and the embedding within Diamond allowed this vision to be realised at breakneck speed and the success of the eBIC model has inspired other synchrotron sites worldwide to follow suit. The Diamond facility


allows scientists to explore complex biological systems in unprecedented detail via the use of powerful cryo-electron microscopes (cryo-EM), exploiting the latest technology and software. The location of eBIC enables scientists to combine their techniques with many of the other cutting-edge approaches that Diamond offers, ranging from fragment-based drug screening through to in-vacuum high-resolution tools for protein structure discovery. l


quality of the data and help with analysis of the data? “It’s clear that there’s still a lot of potential development in the area of electron microscopy, and for me, I think the really interesting possibility – or one of the really interesting possibilities is – to do a different sort of science. It should be feasible, and there’s a lot of technical issues standing in the way still - to join up structural biology with cell biology, so that you can understand what molecules are doing in the very crowded environment of a living cell.”


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