Diamond Concise Annual Review 2021/22

32 33 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 1 / 2 2 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 1 / 2 2 Integrated Facilities and Collaborations A s a world-leading centre for synchrotron science and a cornerstone of a world-class site for scientific discovery and innovation at Harwell, Diamond Light Source has powerful synergies with its neighbouring research institutes and beyond the campus, through collaborations and shared visions. The integrated facilities at Diamond present academic and industrial users with a one-stop- shop for research opportunities, enabling them to combine cutting-edge techniques and capabilities to advance their studies. Several partnerships are highlighted in this section. Integrated Facilities The Membrane Protein Laboratory The Membrane Protein Laboratory (MPL) is a state-of-the-art facility for membrane protein research and is open to user applications from anywhere in the world. Scientists visiting the MPL are supported by state-of -the art equipment and our experienced scientists. 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 in isolation will help us to develop new therapeutics to tackle disease. The MPL has been awarded £1.5m of Wellcome funding to support its research for a further five years. The new funding will enable wider sample support for Diamond beamlines and microscopes and form a foundation for integrative membrane protein structural biology. Two recently published works detail the molecular basis of regulation of bacterial capsule assembly by Wzc 1 and a systematic study of small-scale transient expression of eukaryotic membrane proteins in Expi293F cells 2 . 1. Yang Y. et al. DOI: 10.1038/s41467-021-24652-1 2. Krasnoselska GO et al . DOI: 10.1007/978-1-0716-1406-8_5. Fragment screening (XChem) Alongside the full return of the XChem user programme the XChem team has continued to support the COVIDMoonshot, a global open science, structure enabled drug discovery campaign targeting the SARS-CoV2 main protease. Researchers were able to discover a novel chemical scaffold and developed it into orally bioavailable inhibitors with clinical potential within two years. These inhibitors are currently being evaluated in pre-clinical studies funded by an £8 million award fromWellcome on behalf of the COVID-19 Therapeutics Accelerator 1 . It has been proposed as part of the Diamond-II project to build a new beamline capable of underpinning the next revolution in rational drug discovery over the coming decade. This will allow increased throughput of XChem to both meet user demand for ultra-high-throughput fragment screening and to exploit new experimental modalities. This new beamline K04 will be a flagship project of Diamond-II with building taking place in the run up to the Diamond dark period, minimising the downtime of a key UK infrastructure. Reference 1. https://www.diamond.ac.uk/Home/News/LatestNews/2021/27-09-21. html Highlighted publications: • The COVID Moonshot Consortium. DOI: 10.1101/2020.10.29.339317 • Singh AK et al. DOI: 10.1038/s41467-021-27409-y • Piticchio SG et al . DOI: 10.1021/acs.jmedchem.1c01108 • Bajusz D et al. DOI: 10.1038/s41467-021-23443-y • MahyW et al. DOI: 10.1021/acs.jmedchem.0c01391 XFEL (X-ray Free-Electron Laser) Hub The XFEL Hub at Diamond continues to provide 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. During the year, members of the Hub participated in 13 XFEL experiments at the LCLS in the USA, PAL-XFEL in Korea, or the European XFEL in Germany, mostly by remote access. In March 2022, several members of the XFEL Hub travelled to the LCLS to participate on-site in experiments. The XFEL Hub continued two major projects at Diamond that will establish methods for time-resolved serial crystallography studies using on-demand sample delivery and reaction initiation strategies that can be correlated with tr-XES. The plans also include a deeper collaboration with one or more XFEL facilities which may also host the sample delivery capabilities developed at Diamond. The Hub has also been testing prototypes for sample delivery and XES data collection at Diamond beamline VMXi. Highlighted publications: • Rabe P et al . DOI: 10.1126/sciadv.abh0250 • Butryn A et al. DOI: 10.1038/s41467-021-24757-7 Collaborations The Rosalind Franklin Institute The Diamond-Franklin collaboration in electron imaging and diffraction methods is moving from strength to strength. This past year has seen the delivery of the Franklin's first Titan Krios microscope, Dorothy, and the second- generation plasma focused ion beam (pFIB), called Franklin to enable large volume cellular tomography using novel sample geometries as part of a close collaboration with Thermo Fisher Scientific. The developments are funded by Wellcome through the Electrifying Life Science grant that also funds the development of the HeXI dedicated electron diffraction beamline. The Dorothy microscope was delivered in July 2021, commissioned by Diamond and Franklin staff throughout the summer and is now fully operational in the Rosalind Franklin Institute Hub building offering state of the art capability to Franklin and Diamond scientists. Research Complex at Harwell (RCaH) The Research Complex at Harwell (RCaH) is a joint venture between Diamond and the UK research councils, now UKRI, and provides a research hub for the physical and life sciences. Research facilities or consortia based at RCaH include the Membrane Protein laboratory, the Central Laser Facility (CLF), CCP4 and CCP-EM. This welcomes around 500 scientific visitors and users yearly. RCaH provides most of the wet laboratory space for Diamond, hosts the MPL, the UK XFEL Hub, XChem and the Harwell crystallisation facility. The latter is run as a partnership between Diamond, RCaH and the Rosalind Franklin Institute and provides state-of-the-art facilities which have recently undergone a major upgrade. A new ThermoFisher scientific Glacios™ 200 kV cryo-transmission electron microscope equipped with a falcon IV detector installed at eBIC provides Harwell groups with a state-of-the-art cryo-TEM. This is complemented by dedicated facilities for cryoEM sample preparation. The massive push to SARS-CoV-2 research has led to further work on the SARS-CoV-2 proteases and the use of nanobodies directed against the SARS- CoV-2 spike protein. Catalysis Hub Since 2013 the UK Catalysis Hub has had a Block Allocation Group (BAG) for X-ray Absorption Spectroscopy (XAS) at beamline B18. The BAG is open to every academic working in catalysis in the UK and is designed to support new users to develop proposals and to train them in data analysis. XAS has become one of themost important analytical tools available at Diamond for catalysis research. Over 80 publications have directly resulted from the B18 BAG with recent highlights including the study of aqueous phase reforming (APR) of glycerol which is an important reaction utilising renewable feedstocks such as biomass for the renewable production of hydrogen. The Hub has recently been awarded a further BAG for X-ray Pair Distribution function analysis (XPDF) at beamline I15-1. The new XPDF BAG will introduce new users to XPDF and to develop a broad user base from within the UK catalysis community. Active Materials Laboratory The new Active Materials Laboratory (AML) provides space for radioactive materials research, enabling experiments that were previously impossible in the UK. This 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. The AML has a wet and dry lab for experimental use. Portable beamline equipment can be brought into the AML if required. There is also a characterisation room with a gamma spectrometer and a liquid scintillation counter and a storage room, with safes, fridges, and a freezer for samples to be storedwhen not in use in the labs or beamline. Access is designed principally for those with beamtime at Diamond but can also be obtained without beamtime through the offline facilities scheme. Access is free for non-proprietary research via either route, and currently extra support funding is available through the NNUF II scheme. The University of Manchester at Harwell The University of Manchester at Harwell (UoMaH) is hosted by Diamond. This provides the interface with the Harwell national facilities, enabling UoM researchers to access world-class research at Diamond and all the Science and Technology Facilities Council facilities at Harwell. UoMaH has a growing contingent of Research Fellows based at Harwell: twoworking on resilience and catalysis are sponsored by Diamond, oneworking on fusion is sponsored by ISIS, one working on Data science is sponsored by STFC/SCD and one ‘extreme science’ Fellow is currently being recruited. These strengthen the University’s link with Harwell by bringing their research, networks and new users from industry and Faculty academics to Diamond. In May 2021, UoMaH partnered with Diamond, CLF, UCL, the Health and Safety Executive (HSE) and the UK Health Security Agency (UKHSA) to support the National Core COVID-19 PROTECT Transmission and Environment Study. UoMaH is being funded to manage the study during its final year. InFUSE Prosperity Partnership Technological mobilisation is now required on an unprecedented scale to meet the ambitious national targets for net-zero CO 2 in line with the Paris Climate Agreement. A paradigm shift in the UK’s research and development capabilities is needed to reduce time to market for novel and sustainable solutions. This will require close partnership between academia and industry. One of the key strategies for CO 2 reduction is optimising solid-fluid interfaces. Improving understanding of interfaces will allow researchers to design new materials, devices, and optimised processes that have reduced energy demand or longer life times. InFUSE is a five-year EPSRC (Engineering and Physical Sciences Research Council) funded Prosperity Partnership between Imperial College London, Diamond, and Shell, that will examine how technologies like batteries, lubricants, chemical production, and carbon capture and storage can be improved by understanding interfaces in these systems. The partnership will fund more than 20 new PhD studentships to increase our fundamental understanding of interface behaviours by studying morphology, structure, and chemistry from the atomic to the macroscale, and their dynamic evolution under a range of extreme operational parameters. MPL Laboratory in RCaH.