A High-throughput discovery facility for the Rosalind Franklin Institute

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The Life Sciences sector forms a key part of the UK economy: it employs over 220,000 people, contributes significantly to GDP and UK balance of trade, and is crucial for developing leading-edge treatments for patients. It is underpinned by the UK's world-leading research base in the health and life sciences. Many key research breakthroughs are, in turn, enabled by advances in engineering and physical sciences (EPS) research - which provide ever more sophisticated instrumentation and methods to support the study of living organisms (from microbes to plants, animals and the human body) and biological processes (including both disease pathology and drug action). R&D across all parts of this ecosystem - from fundamental understanding to applied research to product development - is crucial for the delivery of long-term economic growth and continued advances in agriculture, food security, healthcare and public health. Historic models of innovation have often been linear, involving a degree of serendipity. Disruptive technologies and scientific breakthroughs will be accelerated if physical scientists, engineers, life scientists and industry work together, and at scale. This is the domain of the Rosalind Franklin Institute (RFI): with a focal point (Hub) at Harwell Science and Innovation Campus, linked to formal Spokes in leading HEIs across the UK, it will integrate complementary expertise from academia and industry to create a national centre of excellence for methods development at the convergence of the physical and life sciences.A key component of the RFI will be to develop disruptive capabilities to make the discovery of bioactive small molecules more efficient and effective. Bioactive small molecules are important since they dominate (>90%) prescribed drugs and they may be used as tools to provide a better understanding of biology. Current approaches to bioactive molecular discovery tend to focus on the investigation of one design idea at a time via the design, synthesis, purification and evaluation of sets of molecules. Although automation is often used, the stages of the discovery process are poorly integrated. Furthermore, a limited toolkit of chemistry is used to prepare candidate molecules, which means that undue focus is placed on specific classes of molecules: molecules which often do not have ideal properties for drug discovery programmes. The new facility will enable more effective and efficient discovery of high-quality bioactive molecules via rapid design-make-test-analyse cycles in which all stages will ultimately be fully integrated underpinned by an expanded reaction toolkit. The discovery of chemical tools that will be used to investigate disease biology mechanisms is of particular relevance to this project. The project will benefit from other key scientific capabilities at Harwell, including the XChem high-throughput crystallography facility at Diamond Light Source.