Diamond Concise Annual Review 2020/21

28 29 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 Soft CondensedMatter Group T he Soft Condensed Matter Group at Diamond Light Source is comprised of the High Throughput Small Angle X-ray Scattering (SAXS) (B21), the MultimodeInfrared Imaging and Microspectroscopy (MIRIAM) (B22), SAXS and Diffraction (I22) and the Circular Dichroism (CD) Microspectroscopy (B23) beamlines at Diamond Light Source. This unique portfolio of instruments enables studies of non- crystalline materials at micro to meso-scale resolutions that include two-dimensional thin-films (photovoltaics), living mammalian cells, three-dimensional matrices (e.g. metal-organic frameworks, gels and waxes) and nano-particles in non-crystalline states. The group now offers mail-in services for SAXS and CD measurements through UAS (User Administration System) announcements. In addition, I22, B22 and B23 offer off-line access to IRmicroscopy and imaging, CD spectroscopy and SAXS measurements. Studies this year have included observing the cellular impact of drug treatments, developing vaccines that do not require refrigeration for storage and transport, and identifying a new cost-effective approach to Alzheimer’s Disease therapy. Viewing the effect of drug treatment in a single cell A fundamental part of pharmaceutical development is to be able to detect the metabolic changes taking place inside a cell following drug treatment. Currently, most techniques require staining to reveal chemical changes, but this may alter the natural process and producemisleading results. Infrared (IR) microspectroscopy can probe chemical changes in biological matter without the use of dye but the images produced to date are too coarse to see clearly inside a single cell. A teamof researchers investigated a new Synchrotron IR spectroscopic imaging method, developed on the Multimode InfraRed Imaging And Microspectroscopy (MIRIAM) beamline (B22) at Diamond Light Source to probe the molecular changes inside macrophages. These white blood cells produce many tiny fatty droplets when exposed to drugs, but the exact reason for this response is not clear. The study results showed that IR nanospectroscopy can measure a drug’s effect inside a mammalian cell by clearly identifying the chemistry changes within the fatty droplets before and after the application of the drug. This powerful new molecular imaging tool can now be used to understand the responses of macrophages exposed to different drugs. This will help identify new drug candidates and improve the chance of success in delivering better medicines in the near future. Chan K. L. et al. DOI: 10.1021/acs.analchem.9b05759 Developing vaccines that do not need refrigeration Almost all vaccines require refrigeration for storage and transport and a vaccine cold chain has been developed to distribute vaccines worldwide. However, this poses problems in developing nations due to the availability of refrigerators, electricity, infrastructure and staff training. An international team of researchers has developed a novel method of making existing vaccines thermally stable so that they will not depend on cold chain distribution. The process, called ensilication, uses silicon dioxide to create layers of inorganic materials around individual vaccine components which protects the vaccine from temperature degradation. The research team aimed to gain further understanding of the ensilication mechanism by use of in situ Small Angle X-ray Scattering (SAXS) on the time-resolved SAXS & Diffraction beamline (I22) at Diamond Light Source. They studied tetanus toxin C fragment, an inactive component of the tetanus toxin present in the diphtheria, tetanus and pertussis vaccine and were able to show that ensilication maintained the vaccine effect through a three-stage process – nucleation, rapid growth and aggregation. This study explains the mechanism of ensilication of vaccines and how to control the process effectively. This research provides a potential solution for biopharmaceutical stabilisation and could help to increase vaccine transport and administration in all countries around the world. Doekhie A. et al. DOI: 10.1038/s41598-020-65876-3 Assessing a potential new treatment for dementia  There is currently no cure for Alzheimer’s disease, which is associated with the formation of large protein plaques (amyloid-β and tau proteins) in the brain that kill neurons. One therapeutic approach is to block or impair the formation of these plaques and a research group from Lancaster University and the team on the Circular Dichroism beamline (B23) at Diamond Light Source used high- throughput screening techniques to analyse the impact of 88 potential compounds on stabilising protein deposition. The results showed that epinephrine (adrenalin) was superior to the other compounds. Further investigations of chemically similar compounds showed that salbutamol, the well-established asthma drug, interacts with the tau protein substantially, preventing the formation of abnormal tangled clumps that at the early stages are thought to damage brain neurons and progressively induce dementia. Salbutamol could, therefore, be a potential treatment for Alzheimer’s disease and now requires in vitro and eventually a full in vivo evaluation as a potential therapeutic for Alzheimer’s disease. Developing new drugs is slow and very expensive. It is far quicker and cheaper to repurpose clinically approved drugs for other diseases. There is now potential for this approach to be applied to other neurological disorders (such as Parkinson’s and Huntington’s diseases) and any other disorder associated with protein deposits including type 2 diabetes and cancer. Townsend D. J. et al. DOI: 10.1021/acschemneuro.0c00154