Solid-state nuclear magnetic resonance (NMR) spectroscopy is arguably the most powerful technology for providing atomic-level structure and dynamics understanding of molecules and materials. The physical and life sciences communities exploit this analytical science technique extensively to address challenging issues in a wide range of systems relevant to, for example, pharmaceuticals, battery materials, catalysis and protein complexes. Importantly, the advances enabled by solid-state NMR as an analytical technique are continually increasing in line with technological progress in the development of new NMR hardware. In particular, the recent development of commercial 1.2 GHz NMR systems stands to open up exciting new directions in NMR methodological development and deliver unprecedented levels of structural, dynamic and mechanistic information. Seven 1.2 GHz NMR systems are already in operation across Europe with further systems soon to be installed in Germany and the USA. UKRI has recently invested in two such systems at the High-Field Solid-State NMR National Research Facility (NRF) at the University of Warwick, and at the Henry Wellcome Building for Biomolecular NMR Spectroscopy at the University of Birmingham. These systems are expected to be operational in the UK in 2025. The proposed project aims to optimise UKRI's substantial investment in high-field solid-state NMR spectroscopy (notably £23M in 1.2 GHz NMR) by working in partnership with fifteen internationally leading laboratories and seven industry partners. The work will focus on sharing technical and application know-how and expertise to deliver new experimental NMR methodologies and protocols, as well as new scientific insight into complex chemical systems. The project will be divided across three main classes of systems: inorganic materials, biosolids and pharmaceuticals, with researchers working in each of these fields. New experimental methodologies will be designed and investigated within the NRF itself, and also exploiting the wide range of NMR hardware and expertise available in the co-investigator team and partner institutions. As well as the main focus of ultra-high field NMR, the NRF and partner institutions will provide access to specialist NMR hardware such as very high- and low-temperature apparatus (100 - 1000 K) to enable complex structural and dynamic phenomena to be probed in greater detail. The techniques developed within the project will enable the capabilities of ultra-high field NMR to be fully realised and will lead to new atomic-level insights into systems of relevance to the wider scientific community and industrial partners. The dissemination of the research and the interaction with international academic and industry partners will help to maintain the UK's position as a world leader in solid-state NMR research.

Harnessing the immune system to treat cancer has revolutionised survival outcomes for many patients. Immune checkpoint inhibitor therapies which unleash the brakes from immune cells to kill cancer cells, have become standard of care for many cancer subtypes. The success of existing, emerging and future immunotherapies and their routine use in the NHS is dependent on the appropriate tools, data and technology to rationalise their use and manage their side effects. Nevertheless, almost no biomarkers today can effectively distinguish responders from non-responders, predict toxicity, or guide treatment choices. Moreover, existing datasets lack standardization, suffer from sampling biases, and fail to integrate 'multi-omics' data with clinical information. Our platform, MANIFEST, leverages existing and also novel scalable methodologies to provide deep profiling of each patient receiving immunotherapy and will deliver on multimodal data integration and modelling. We represent a diverse group of UK-wide experts in cancer research and clinical care comprising 6 major NHS trusts, 14 academic institutes and universities, and with strong upfront top-up investment (>£ 12 million) from industry partners (namely IMU Biosciences, Guardant Health, Natera, Roche-imCORE, Roche-Sequencing, M:M Bio and Microbiotica; among others). To demonstrate the utility of the MANIFEST platform, we will deliver exemplar projects encompassing multiple tumour types (melanoma, renal cell carcinoma, bladder cancer and triple negative breast cancer), where prediction of treatment outcomes and toxicities to both standard of care and emerging immunotherapies remains a significant unmet need. Specifically, we have access to pre-existing longitudinal samples of >3,000 patients across 10 reported studies (RAMPART, MITRE, PRISM, EXACT, CAPTURE, PaVeMenT, ALEXANDRA, neoTRIP, ABACUS and ABACUS-2). In parallel, we will utilise existing governance at partner NHS sites for prospective sample collection (blood, stool and tumour) and processing. With a tiered approach, we aim to profile patient and tumour samples at scale (~3,000 patients over 3 years). We will implement standard of care diagnostic workflows for high-volume biomarker discovery (Tier 1). We reserve in-depth profiling, through Tiers 2 and 3 participation, to further characterise tumours including discovery-focused techniques, such as high-dimensional peripheral immune profiling, liquid biopsy (cfDNA, immune methylation profiling), and spatial image-profiling approaches coupled with molecular profiling (WES, bulk&long-read RNAseq, TCR&BCRseq). Finally, for selected patients, we will apply our expertise in Representative Sequencing (RepSeq), a novel tumour sampling methodology which overcomes pervasive sampling bias in solid tumours; and pre-clinical modelling through patient-derived tumour fragments (PDTFs) for drug sensitivity screening. Finally, we will deploy a team of 12 experts in artificial intelligence and machine learning to deliver on multimodal data acquisition and integration in our in-house Trusted Research Environment (TRE). We are also excited to be teaming up with the National Pathology Imaging Co-operative (NPIC) and Genomics England (GEL) to synergise efforts in translating discoveries for patient benefit.

This user-need CDT will equip graduates with the skills needed by the UK formulation industry to manufacture the next generation of formulated products at net zero, addressing the decarbonisation needs for the sector and aligning with this EPSRC priority. Formulated products, including foods, battery electrodes, pharmaceuticals, paints, catalysts, structured ceramics, thin films and coatings, cosmetics, detergents and agrochemicals, are central to UK prosperity (sector size > £95bn GVA in 2021) and Formulation Engineering is concerned with the design and manufacture of these products whose effectiveness is determined by the microstructure of the material. Containing complex soft materials: structured solids, soft solids or structured liquids, whose nano- to micro-scale physical and chemical structures are highly process dependent and critical to product function, their manufacture poses common challenges across different industry sectors. Moving towards Net Zero manufacture thus needs systems thinking underpinned by interdisciplinary understanding of chemistry, processing and materials science pioneered by the CDT for Formulation Engineering at the University of Birmingham over the past twenty years, with a proven delivery of industrial impact evidenced by our partner's letters of support and three Impact Case Studies ranked at 4* in the recent Research Excellence Framework in 2021. A new CDT strategy has been co-created with our industry partners, where we address new user-led research challenges through our theme of Formulation for Net Zero ('FFN0), articulated in two research areas: 'Manufacturing Net Zero (MN0)', and 'Towards 4.0rmulation'. Formulation engineering is not taught in first degree courses, so training is needed to develop the future leaders in this area. This was the industry need that led to the creation of the CDT in Formulation Engineering, based within the School of Chemical Engineering at Birmingham. The CDT leads the field: we won for the University one of the 2011 Diamond Jubilee Queen's Anniversary Prizes, demonstrating the highest national excellence. The UK is a world-leader in Formulation; many multinational formulation companies base research and manufacture in the UK, and the supply of trained graduates, and open innovation research partnerships facilitated by the CDT are critical to their success. The CDT receives significant industry funding (>£650k pa), supported by 31 industry partners including multinationals: P&G, Colgate, Unilever, Diageo, Devro, Fonterra, Samworth Bros., Jacobs Douwe Egberts, Nestle, Pepsico, Mondelez, GSK, AZ, Lonza, Novartis, BMS, BASF, Celanese, Croda, Innospec, Linde/BOC, Origen, Imerys, Johnson Matthey, Rolls-Royce/HTRC, JLR Lucideon and SMEs: Aquapak, CALGAVIN and ITS/StreamSensing. Intra and cross cohort training is central to our strategy, through our taught programme and twice-yearly internal conferences, industry partner-led regional research meetings, student-led technical and soft skills workshops and social events and inter CDT meetings. We have embedded diversity and inclusion into all of our projects and processes, including blind CV recruitment. Since 2018 our cohorts have been > 50% female and >35% BAME. We will co-create training and research partnerships with other CDTs, Catapult Centres, and industry, and train at least 50 EngD and PhD graduates with the skills needed to enhance the UK's leading international position in this critical area. The taught programme delivers a common foundation in formulation engineering, specialist technical training, modules on business, entrepreneurship and soft skills including a course in Responsible Research in Formulation. We have obtained promises of significant industry and University funding, with 67 offers of projects already. EPSRC costs will be 44% of the cash total for the CDT, and ca. £27% of the whole cost when industry in-kind funding is included.

We will train a cohort of students at the interface between the physical and computer sciences to drive the critically needed implementation of digital and automated methods in chemistry and materials. Through such training, each student will develop a common language across the areas of automation, AI, synthesis, characterization and modelling, preparing them to become both leader and team player in this evolving and multifaceted research landscape. The lack of skilled individuals is one of the main obstacles to unlocking the potential of digital materials research. This is demonstrated by the enthusiastic response toward this proposal from our industrial partners, who span sectors and sizes: already 35 are involved and we have already received cash support corresponding to over 27 full studentships. This proposal will deliver the EPRSC strategic priority "Physical and Mathematical Sciences Powerhouse" by training in "discovery research in areas of potential high reward, connecting with industry and other partners to accelerate translation in areas such as catalysis, digital chemistry and materials discovery." The CDT training programme is based on a unique physical and intellectual infrastructure at the University of Liverpool. The Materials Innovation Factory (MIF) was established to deliver the vision of digital materials research in partnership with industry: it now co-locates over 100 industrial scientists from more than 15 companies with over 200 academic researchers. Since 2017, academics and industrial researchers from physical sciences, engineering and computer sciences have co-developed the intellectual environment, infrastructure and expertise to train scientists across these areas. To date, more than 40 PhD projects have been co-designed with and sponsored by our core industrial partners in the areas of organic, inorganic, hybrid, composite and formulated materials. Through this process, we have developed bespoke training in data science, AI, robotics, leadership, and computational methods. Now, this activity must be grown scalably and sustainably to match the rapidly increasing demand from our core partners and beyond. This CDT proposal, developed from our previous experience, allows us to significantly extend into new sectors and to a much larger number of partners, including late adopters of digital technologies. In particular, we can now reach SMEs, which currently have limited options to explore digitalization pathways without substantial initial investment. A distinctive and exciting training environment will be built exploiting the diverse background of the students. Peer learning and group activities within a cross-disciplinary team will accelerate the development of a common language. The ability to use a combination of skills from different individuals with distinct domain expertise to solve complex problems will build the teams capable of driving the necessary change in industry and academia. The professional training will reflect the diversity of career opportunities available to this cohort in industry, academia and non-commercial research organizations. Each component will be bespoke for scientists in the domain of materials research (Entrepreneurship, Chemical Supply Chain, Science Policy, Regulatory Framework). External partners of training will bring different and novel perspectives (corporate, SMEs, start-ups, international academics but also charities, local authorities, consultancy firms). Cohort activities span the entire duration of the training, without formal division between "training" and "research" periods, exploiting the physical infrastructure of MIF and its open access area to foster a strong and vital sense of community. We will embed EDI principles in all aspects of the CDT (e.g. recruitment, student well-being, composition of management, supervisory and advisory teams) to make it a pervasive component of the student experience and professional training.

Maintaining sustainable productivity of pharmaceutical research and development is one of the most significant challenges faced by this major UK industry. Pre-clinical models for testing drug safety and efficacy are poorly predictive of human response, making our ability to translate new scientific discovery to impactful therapy extremely costly and time consuming. Organ-chips are small, bioengineered devices which replicate important aspects of human health and disease, and thus provide the predictivity of human response required to transform therapeutic delivery. The organ-chip industry is one of the fastest growing worldwide, as the transformative potential of organ-chip technology is realised. For the UK to ensure ongoing growth and productivity of the pharmaceutical industry, it is imperative we deliver a workforce able to advance this technology and bring it into use, to drive successful healthcare innovation. COaCT sets a transformative vision to bring together the full stakeholder community in organ-chip technology, to collectively develop and deliver a training programme designed to equip graduates with the skills and knowledge required to be the next generation of leaders in organ-chip technology and advance the technology into regulatory use. We focus on three core areas: 1. delivering the technical skills required to design, manufacture and advance organ-chip models: Organ-chip models are microfluidic devices, in which the physics of managing organ growth and drug delivery are different to those in standard cell cultures. We provide training to ensure students understand how to work with a wide range of commercial organ-chip systems and build their own devices, appreciating the specific biosensing, nano-patterning, mechanobiology, microfluidics and microfabrication requirement of organ-chip systems, and the rationale and decision making associated with selecting different approaches, so they are fully prepared to work across the sector in future roles. 2. ensuring students are equipped with the broader understanding of the societal implications of the technology, and the regulatory and policy changes which will be necessary to ensure impactful delivery. There is clear potential for organ-chip approaches to revolutionise therapeutic discovery, but for the technology to achieve its potential, it is imperative that the field fully considers and responds to the societal and regulatory environment as it evolves and develops, thus our future leaders must be fully trained in this area. 3. providing a focus on transferable skills training, to help students develop into effective future leaders in this field: The rapid growth of organ-chip technology offers exciting future opportunities for researchers shaping the field. To be effective in driving the field, it is important graduates possess the transferable skills to lead teams and companies designing or implementing organ-chip technology, and are able to communicate effectively with the broad range of stakeholders involved. Our stakeholder community brings together the pharmaceutical and organ-chip industries, varied medicine-related regulatory bodies, policy groups, and charities, all with a strong commitment to deliver organ-chip technology. The COaCT investigator team have been leading the efforts of this stakeholder community to coordinate and drive organ-chip research for the last 5 years, though leadership of the UK organ-on-a-chip technologies network. Indeed, the ideas for the CDT scope and training remit have been developed collectively through those discussion panels and workshops.