Diamond Annual Review 2021/22

120 121 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 Industrial Liaison Industrial Liaison Office A nother extraordinary year has passed and life at Diamond Light Source is gradually returning to normal. It has been a great pleasure to see our valued clients returning in person for experiments and although there have been fewer in personmeetings and events this year, the Industrial Liaison team are looking forward to getting out and about andmeeting in person over the coming year. The industrial programme at Diamond is thriving and we have had our busiest year to date. Diamond is now working with 200+ clients in 22 countries. The many years of preparation and work in establishing efficient and reliable workflows for remote and mail-in experiments have shown their worth over the last couple of years, enabling the team to respond quickly and provide seamless support for our clients as the world around us pivoted to remote working. Our data collection services across the techniques available at Diamond continue to be extremely popular and have gained widespread adoption with our clients who value the flexible approach and trust us to collect precious data with the same professionalism and care that they would apply themselves. The physical science industrial programme is now fully operational and as restrictions on the complexity of experiments and numbers of people participating in experiments are eased, we are excited to take part in complex in situ team experiments once again and continue to build our successful programme for diffraction, spectroscopy, scattering and imaging experiments. The life sciences industrial programme was only very briefly paused in early 2020 and since then has continued to develop and grow at a great pace. Demand remains high for our macromolecular crystallography, cryo-Electron Microscopy (cryo-EM), fragment screening and small angle scattering services and a new crystallisation service has been launched to help support clients at the early stages of drug discovery giving access to Diamond’s facilities and expertise. This year we have welcomed two new members of the ILO team, both providing technical expertise, professional efficiency and a welcoming smile to our cryo-EM clients. Dr Hazel Aitkenhead joins us from the University of Oxford and is experienced in protein production and high throughput discovery science. Dr Manikandan (Mani) Karuppasamy joins us from the Tata Institute for Genetics and Society in Bangalore, India and brings a wealth of experience of cryo-EM studies on a range of industrially relevant systems. Although our primary focus remains our client projects, the ILO team continues with our own research and this year ILO PhD student Paul Edwards, Elizabeth Shotton, Anna Kroner and the University of Leeds team, led by Prof. Sven Schroeder, were the first users of the Versatile Soft X-ray (VerSoX) beamline (B07-B). The team used B07-B to measure the C, N and O K-edge spectra of a range of solid, organic crystal systems using Near Edge X-Ray Absorption Fine Structure (NEXAFS). The results were used to test the hypothesis that NEXAFS can be used as a quick diagnostic tool to characterise pharmaceutical materials where crystallographic methods may not give a definitive answer and provide an alternative route for characterisation of to complex bespoke solutions. Please do not hesitate to contact us on [email protected] to discuss your analytical needs, we are happy to help. References: 1. Basford, P. A. et al. Does the age of pharmaceuticals matter? Undetectable hydrate seeds impact hydration behavior. Crystal Growth & Design , 21 1912–1916 (2021). DOI: 10.1021/acs.cgd.1c00100 2. Okolo, C. A. et al. Correlative imaging using super-resolution fluorescence microscopy and soft X-ray tomography at cryogenic temperatures provides a new way to assess virosome solutions for vaccine development. Journal of Microscopy , 284 214–232 (2021). DOI: 10.1111/ jmi.13054 these complex materials. Undertaking complex experiments on a brand-new facility while working under tight COVID restrictions is a significant challenge and we thank all the teams at Diamond and Leeds whose hard work ensured a successful outcome. A study of the hydration behaviour of fluconazole, an antifungal drug, known to crystallise in at least five polymorphs was undertaken by Leigh Connor in collaboration with scientists from Pfizer and the University of Manchester 1 . The team used high resolution powder diffraction studies on the High Resolution Powder Diffraction beamline (I11) to show that both age and polymorphic form impact the drug’s kinetic stability to hydration. In particular, an initially undetectable monohydrate form of the drug was shown to have a seeding effect which impacted the hydration kinetics. Collaborating with Activirosomes Ltd, Claire Pizzey and the B24 beamline team published the results of a large project aimed at characterising a novel vaccine platform using a 3D correlative microscopy approach. Active virosomes (AVs) are essentially novel vaccine formulations that present on their surface selected viral proteins as antigens, acting to provoke an “anti-viral” immune response. AVs are internalised by host cells and deliver a viral payload of genes used to express viral antigens intracellularly. These can then be transported to the host cell surface resulting in a second wave of antigen exposure and a more potent immuno-stimulation. The target virus antigens selected for this work were category B priority pathogens, Chikungunya and Zika viruses. To date, there is no drug treatment nor vaccine available for immunisation against these pathogens; therefore, the development and optimisation of appropriate vaccines remains an urgent requirement for world health. A 3D correlative microscopy approach, combining cryo Structured Illumination Microscopy (cryoSIM) and cryo-soft X-ray tomography, allowed visualisation of the 3D ultrastructure and antigen loading of AV populations (with and without viral payload) and assessment of morphological variations across batches 2 . Preliminary results also verified antigen expression on the surface of host cells, demonstrating the effectiveness and robustness of the technique for characterising novel vaccine formulations such as AVs. Financial support for the Activirosomes Ltd project was provided by the Bridging for Innovators (B4I) scheme through STFC. An ongoing collaboration with Activirosomes Ltd will continue to increase productivity by optimising protocols for commercial vaccine analysis. Diamond continues to support our industrial clients across a wide range of techniques and facilities with experiments ranging from routine analysis The eBIC for Industry team (L-R): Jason van Rooyen, Hazel Aitkenhead and Mani Karuppasamy. Jitka Waterman loading pucks for MX experiments. Alex Dias and Ailsa Powell preparing pucks for XChem experiments. Anna Kroner conducting X-ray spectroscopy experiments. Elizabeth Shotton, Anna Kroner and Paul Edwards, along with the B07-B team and the Leeds team led by Sven Schroeder, were first users on B07-B.