Diamond Concise Annual Review 2020/21

30 31 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 0 / 2 1 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 0 / 2 1 Integrated Facilities and Collaborations D iamond Light Source collaborates closely with neighbouring research institutes and companies on the Harwell Science and Innovation Campus and beyond. The integrated facilities at Diamond present academic and industrial users with a one-stop-shop for research opportunities. These facilities and partnerships bring together expertise from UK universities, research institutes and industry to help tackle 21 st century challenges. Integrated Facilities The Membrane Protein Laboratory (MPL) The MPL is a state-of-the-art facility for membrane protein research and is open to user applications from anywhere in the world. Since its inception, the MPL has supported visiting researchers in investigating proteins that are embedded in cell membranes. Membrane proteins are important targets for biomedicine with over half of all medicines altering membrane protein function. Understanding the structure and function of these proteins will help develop future disease therapies. The MPL has a dedicated laboratory close to the experimental end stations and electron microscopes, which greatly enhances scientists’ability to characterise these targets. A recent study 1 used MPL facilities to investigate a series of Archarhosdopsin-3 (AR3) structures which opens the way for the development of new tools in the fields of neuroscience, cell biology and beyond. Another study used in vitro and in cellulo approaches to characterise disulphide bonding in the major outer membrane protein (MOMP), an important Chlamydia vaccine target 2 . References: 1. Bada Juarez J. F. et al. DOI: 10.1038/s41467-020-20596-0 2. Danson A. E. et al. DOI: 10.3390/biology9100344 Fragment screening (XChem) The XChem facility stayed open throughout lockdown for experiments aimed at accelerating development of new treatments for COVID-19. Early in the pandemic, XChem joined a collaboration to identify fragment compounds bound to the Main protease, a key enzyme in the life cycle of the SARS-CoV-2 virus, to provide templates for designing bespoke molecules to block the enzyme. The data stimulated much interest, and XChem became a founding partner of the COVID Moonshot, a global non-profit initiative aiming to develop a novel antiviral drug by crowdsourcing designs of new inhibitors from chemists worldwide who could mine the Diamond data. The project continues to release its data in real-time, which has driven rapid progress. Alongwith collaborators, the XChem teamperformed screens against a further seven COVID-19 proteins, to trigger further productive drug discovery efforts. By April 2021, combined international efforts had discovered 234 fragment compounds that directly bind to sites of interest on the surface of this cohort of seven proteins. Many of these data are already public, providing large numbers of starting points for designing compounds as antivirals. Highlighted publications • Douangamath A. et al. DOI: 10.1038/s41467-020-18709-w • Chodera J. et al. DOI: 10.1038/s41557-020-0496-2 • Schuller M. et al. DOI: 10.1126/sciadv.abf8711 • Newman J. A. et al. DOI: 10.1101/2021.03.15.435326 XFEL (X-ray Free-Electron Laser) Hub The XFEL Hub continues to provide expertise and support to the UK community engaged in serial crystallography and XFEL-related life science research. The Hub also organises the Block Allocation Group ‘Dynamic Structural Biology at Diamond and XFELs’for serial crystallography and time-resolved studies. Nearly all XFEL beamtime awards over the past year have been impacted by the COVID-19 pandemic. Since February 2020, our XFEL activities included more than a dozen beamtime awards fielded at XFELs SACLA (Japan), PAL-XFEL (South Korea), LCLS (USA), and the European XFEL (Germany). From August 2020 the Hub participated in all XFEL beamtime through remote connections, including the Hub-led COVID-19 experiments at LCLS and the European XFEL. The Hub also initiated major projects to establish strategies for time-resolved Macromolecular Crystallography studies with on-demand sample delivery and reaction initiation methods that can be correlated with X-ray Emission Spectroscopy. Dr Allen Orville and team created an updated science case for a UK-based X-ray Free Electron Laser (UK-XFEL). More information can be found at: www.clf.stfc . ac.uk/Pages/UK-XFEL-science-case Highlighted publications • Orville A. M. DOI: 10.1016/j.sbi.2020.08.011 • Srinivas V. et al. DOI: 10.1021/jacs.0c05613 • IbrahimM. et al. DOI: 10.1073/pnas.2000529117 • Sethe Burgie E. et al. DOI: 10.1073/pnas.1912041116 The University of Manchester Diamond has joined a new partnership of UK universities to help researchers carry out experiments using X-ray Computed Tomography (XCT). Funded by the Engineering and Physical Sciences Research Council (EPSRC), the National Research Facility for X-ray Computed Tomography (NXCT) provides world class 3D imaging facilities and data analysis, research knowledge and technical experience. NXCT’s mission is to provide access and expert support for both academia and industry. Diamond will work with NXCT to help guide potential users toward the right facilities for their studies. NXCT users will access Diamond via the standard routes and will benefit from the support of a joint appointee between Diamond andManchester, a post funded 50%by the EPSRC grant to specifically support NXCT activities. The University of Manchester at Harwell (UoMaH) is hosted by Diamond and provides the interface with the Harwell national facilities. The core technical team specialises in developing sample environments and equipment in support of experiments, involving high risk materials and extreme sample environments, fielded at the national facilities. UoMaH also has a growing contingent of research fellows based at Harwell. They strengthen the University’s link with Harwell by bringing their research, networks and new users from Industry and Faculty academics to Diamond. The Faraday Institution Diamond is involved in several Faraday Institution projects including: • The displacement and strain with battery electrodes and developments in super-resolution techniques and machine learning to enhance correlative imaging. • The Faraday CATMAT project to increase understanding of cathode materials, in particular using oxygen-redux materials to increase cathode energy density using the I21 beamline. The project is also developing 3D spectroscopic and structural imaging on beamline I14 to aid characterisation of these materials. • The Degradation project uses high-resolution X-ray Powder Diffraction on beamline I11 to obtain valuable information on the structural evolution of novel, high energy-density electrode materials, in situ . The Long Duration Experiment (LDE) facility has been used to perform long-term, in operando cycling experiments, providing a better understanding of the degradation mechanisms leading to battery capacity loss and poor cycle life. • I15-1, the X-ray Pair Distribution Function (XPDF) beamline, is a collaborator in the Recycling, Degradation and SOLBAT projects. Recent developments in cell design at I15-1 will facilitate fast operando XPDF studies for Faraday researchers investigating next generation cathodes, solid-state batteries and recycled battery materials. Collaborations The Rosalind Franklin Institute Diamond is a founding member of the Rosalind Franklin Institute (The Franklin) with ten universities and UKRI-STFC. The Institute is dedicated to bringing about transformative changes in life science through interdisciplinary research and technology development. Last year the Wellcome Trust awarded The Franklin, along with partners MRC Laboratory of Molecular Biology (MRC LMB) and Diamond, a £25m grant to support the development of three new electron imaging technologies that will have the capacity to revolutionise how we see life, pushing the boundaries of imaging in life science. Diamond’s share of the grant is to fund the development of a Hybrid electron X-ray Instrument (HeXI), which is set to play a major role in drug discovery efforts. HeXI will make electron diffraction accessible to Diamond’s existing life science users as well as attract new users to study pharmaceutical compounds and their binding. Other collaborations include: • The Amplus project with Thermofisher Scientific to develop instruments to deliver a revolution in cryo-electron tomography – using electron microscopy to build up three-dimensional models inside the cell. • SPT Labtech and Diamond are developing methods for sample preparation using SPT Labtech’s chameleon, an automated system for next generation cryo-EM sample preparation. Research Complex at Harwell (RCaH) RCaH is a joint venture between Diamond and UK Research and Innovation (UKRI) and provides a research hub on the Harwell campus for the physical and life sciences. It currently has over 180 researchers fromUK universities working in a mix of wet and dry laboratory space supported by research grants. In addition, there is a mix of research facilities or consortia based at RCaH including Diamond’s Membrane Protein Laboratory (MPL), the Central Laser Facility (CLF), CCP4 and CCP-EM. RCaH provides the majority of the wet laboratory space for Diamond group leaders and also hosts the UK XFEL Hub, XChem and the Harwell crystallisation facility. The last year has been extremely busy for RCaH to allow COVID-19 research to continue, including the first fragment screening data from Diamond. Active Materials Building Construction of a new dedicated Active Materials Building (AMB) started in 2020. The new facility, which should open later this year, will provide space for radioactive materials research, enabling experiments that were previously impossible in the UK. This new laboratory is part of phase 2 of the Government’s National Nuclear User Facility (NNUF) project to provide state-of-the-art experimental facilities for research and development in nuclear science and technology. Representation of the chemicals binding to the main protease of the SARS-CoV-2 virus.