It is now clear that biological functions or diseases arise from complex interactive networks operating on many different scales. The translational work needed to transform promising new drugs and therapies into commercial products will increasingly require predictive mathematical and computational modelling at the systems level. The Systems Approaches to Biomedical Science (SABS) Centre aims to meet this demand by training a new generation of responsive research leaders with the ability to generate and apply novel physical and mathematical techniques to solve research problems of relevance to the pharmaceutical, biomedical, biotechnology and related sectors. SABS will address these industry-relevant scientific questions from the real world, and explore them through genuine academic-industrial collaborations. SABS will provide training and research across a wide range of areas, including the design and testing of new chemical and biological entities, modelling biological systems, and robust analysis of complex datasets. Such cross-disciplinary work will introduce students to cutting edge organic chemistry, chemoinformatics, chemical and synthetic biology, biophysics, advanced computational simulation, bioinformatics, data mining, statistical analysis, physical and structural study of biomolecules, and mathematical modelling. Over the last 4 years the SABS team have created a wide network of contacts within Oxford and across industry. SABS will continue to work closely with its partner companies (AstraZeneca, Diamond Light Source, e-Therapeutics, Evotec, GE Healthcare, GlaxoSmithKline, Hoffmann LaRoche, InhibOx, Lilly UK, Microsoft, Novartis, Pfizer, Structural Genomics Consortium and UCB), and with 14+ departments across the University. Every SABS student will be co-supervised and co-funded by industry and will be fully exposed to the industrial context of their research in both the taught programme, and in their industry-based research projects. They will develop skills in project management, strategic planning, leadership, team working, commercial awareness, and problem solving all of which will be required to translate innovations in basic and medical science into commercial product development. SABS will continue to use its ground-breaking and, currently, unique Open Innovation IP agreement, which allows all participants in the SABS consortium to see the results of all research projects. Participating companies regard it as a trail-blazing model for the future of industry-academia collaboration, because it simplifies inter-company research collaboration within the consortium and improves the existing business process for innovation and academic collaborations. From an academic perspective, it allows the students to participate in impactful industrial research whilst still gaining the benefits of research discussion with their peer cohort. Oxford University has made substantial investments both in infrastructure for graduate training and all research areas associated with SABS. It actively promotes interdisciplinary research with external collaborators, and is currently investing heavily in the new Target Discovery and Big Data institutes. SABS has demonstrated very strong user pull, and an ability to recruit new companies; three organisations are currently in the process of joining. In this new bid the companies have doubled their cash contribution per student to £30k, and will also cover all associated research and travel costs (currently averaging £8k per student); a clear commitment to the continuation of the SABS centre. Our minimum cohort size of 14 means industry will make a minimum cash contribution to student funding of £2.1m and a further £560k to research costs.

The EUbOPEN partnership of excellence will aim to generate the largest freely available set of high-quality chemical inhibitors for human proteins. These compounds will include chemical probes for solute carriers (SLCs), E3-ubiquitin ligases (E3s) and other proteins, and a chemogenomic library (CGL) of 3000-5000 compounds covering one third of the druggable genome. All compounds in the sets will be comprehensively characterised defining their selectivity, potency and cellular activity. The compounds will be annotated with a series of established and novel biochemical and cell-based assays, including many derived from primary patient cells. Diseases of particular focus will be inflammatory bowel disease, cancer and neurodegeneration. EUbOPEN partners have proven track records leading large international open science projects, developing unencumbered key reagents, and exploring new target areas. A strong commitment to open data and open science will accelerate the dissemination of knowledge and reagents as well as mitigate ethical issues that might arise by working with patient-derived cells. EUbOPEN will partner extensively with other large projects (e.g. ReSOLUTE, Illuminating the Druggable Genome) to minimize duplication of effort and to maximize global coordination. EUbOPEN will provide via the EFPIA partners the public access to industry’s deep medicinal chemistry skills. Sustainability of the project’s resources will be ensured through already established partnerships with chemical vendors and cheminformatics/database providers, which will ensure the long-term availability of the new chemical tool sets, all associated profiling data and established protocols. The EUbOPEN project will form the foundation for future efforts to generate chemical modulators for the entire druggable genome and will develop new technologies significantly shortening hit and lead identification processes.

SMASHfestUK seek Nucleus award funding for the purposes of developing a physical science specific, immersive theatrical experience for the purposes of ultra-deep engagement with STFC scientists, research and facilities. "Space Plague" is aimed at engaging, young people and their families, and will be specifically focussed on working with culturally diverse socially-economically disadvantaged communities in London and Bradford initially. SMASHfestUK has previously developed disaster-based and narrative-lead STEM festivals over 4 years, which have been very successful in reaching disadvantaged and under-represented audiences and attracting audiences who are 60-70% BME and up to 80% fifth quintile POLAR postcodes (most deprived). Some of this work has been funded and supported by previous STFC Spark awards, providing learnings which we are basing this application on. Evaluation evidence suggest strongly that the disaster-themed narrative angle of the festival is a very successful way of engaging young people, particularly those who do not normally engage with science. The festival format however, makes it very resource-heavy, limiting the ability of the festival to travel and reach wider audiences effectively and the level of engagement with specific research can be variable, depending on factors such as volunteers knowledge. "Space Plague" will be an interactive experience which will use methodologies developed from immersive theatre, escape rooms and existing SMASHfestUK interactive installations to create a fully immersive production in which audiences will take part in a performance, carrying out experiments, solving clues and finding solutions to problems that threaten the future of humankind. Although fictional, the storyline will be based on real, (possible) events and the solutions will come through engagement (within the narrative) with STFC researchers and facilities. We will partner with researchers and facilities to develop the story and script. A single "performance" lasting around 60 minutes will process 60 visitors who will experience 3 linked storylines, (each with its own interactive scientific elements) in which visitors help prevent a coming disaster. It is envisaged that the performance will form a central experience at Science festivals (repeated multiple times daily), and that real scientists will feature as live characters in the stories (semi-fictionalised). We will also create filmed assets with the researchers and the research facilities so that it can be toured around more rural areas and also into schools on smaller budgets, if individuals are unable to participate live. In this way we will create an activity which can be enjoyed with a full "cast" featuring live scientists and actors at large events such as festivals, but can also be customised for touring to schools or rural areas in a more resource friendly manner, extending the life-span and audience reach of the piece. We seek funding to develop and deliver the specific storyline for the first iteration of Space Plague - the core of the story - which will form a standalone performance/experience. We envisage that other storylines could be attached to it in the future to create sequels and new "episodes". In this sense we intend to create a production which is customisable, scaleable and can be distributed and experienced in different ways depending on the available resources. Although the title of the piece is Plague, these modules specifically revolve around real STFC funded research and facilities in the UK. The performances will be piloted, developed and performed across 3 festivals, Bradford Science Festival (2019 and 20) and SMASHfestUK (Deptford) in 2020.