Large-Area Electronics is a branch of electronics in which functionality is distributed over large-areas, much bigger than the dimensions of a typical circuit board. Recently, it has become possible to manufacture electronic devices and circuits using a solution-based approach in which a "palette" of functional "inks" is printed on flexible webs to create the multi-layered patterns required to build up devices. This approach is very different from the fabrication and assembly of conventional silicon-based electronics and offers the benefits of lower-cost manufacturing plants that can operate with reduced waste and power consumption, producing electronic systems in high volume with new form factors and features. Examples of "printed devices" include new kinds of photovoltaics, lighting, displays, sensing systems and intelligent objects. We use the term "large-area electronics" (LAE) rather than "printable electronics" because many electronic systems require both conventional and printed electronics, benefitting from the high performance of the conventional and the ability of the printable to create functionality over large-areas cost-effectively. Great progress has been made over the last 20 years in producing new printable functional materials with suitable performance and stability in operation but despite this promise, the emerging industry has been slow to take-off, due in part to (i) manufacturing scale-up being significantly more challenging than expected and (ii) the current inability to produce complete multifunctional electronic systems as required in several early markets, such as brand enhancement and intelligent packaging. Our proposed Centre for Innovative Manufacturing in Large-Area Electronics will tackle these challenges to support the emergence of a vibrant UK manufacturing industry in the sector. Our vision has four key elements: - to address the technical challenges of low-cost manufacturing of multi-functional LAE systems - to develop a long-term research programme in advanced manufacturing processes aimed at ongoing reduction in manufacturing cost and improvement in system performance. - to support the scale-up of technologies and processes developed in and with the Centre by UK manufacturing industry - to promote the adoption of LAE technologies by the wider UK electronics manufacturing industry Our Centre for Innovative Manufacturing brings together 4 UK academic Centres of Excellence in LAE at the University of Cambridge (Cambridge Integrated Knowledge Centre, CIKC), Imperial College London (Centre for Plastic Electronics, CPE), Swansea University (Welsh Centre for Printing and Coating, WCPC) and the University of Manchester (Organic Materials Innovation Centre, OMIC) to create a truly representative national centre with world-class expertise in design, development, fabrication and characterisation of a wide range of devices, materials and processes.

By 2025 targeted biological medicines, personalised and stratified, will transform the precision of healthcare prescription, improve patient care and quality of life. Novel manufacturing solutions have to be created if this is to happen. This is the unique challenge we shall tackle. The current "one-size-fits-all" approach to drug development is being challenged by the growing ability to target therapies to only those patients most likely to respond well (stratified medicines), and to even create therapies for each individual (personalised medicines). Over the last ten years our understanding of the nature of disease has been transformed by revolutionary advances in genetics and molecular biology. Increasingly, treatment with drugs that are targeted to specific biomarkers, will be given only to patient populations identified as having those biomarkers, using companion diagnostic or genetic screening tests; thus enabling stratified medicine. For some indications, engineered cell and gene therapies are offering the promise of truly personalised medicine, where the therapy itself is derived at least partly from the individual patient. In the future the need will be to supply many more drug products, each targeted to relatively small patient populations. Presently there is a lack of existing technology and infrastructure to do this, and current methods will be unsustainable. These and other emerging advanced therapies will have a critical role in a new era of precision targeted-medicines. All will have to be made economically for healthcare systems under extreme financial pressure. The implications for health and UK society well-being are profound There are already a small number of targeted therapies on the market including Herceptin for breast cancer patients with the HER2 receptor and engineered T-cell therapies for acute lymphoblastic leukaemia. A much greater number of targeted therapies will be developed in the next decade, with some addressing diseases for which there is not currently a cure. To cope, the industry will need to create smarter systems for production and supply to increasingly fragmented markets, and to learn from other sectors. Concepts will need to address specific challenges presented by complex products, of processes and facilities capable of manufacture at smaller scales, and supply chains with the agility to cope with fluctuating demands and high levels of uncertainty. Innovative bioprocessing modes, not currently feasible for large-scale manufacturing, could potentially replace traditional manufacturing routes for stratified medicines, while simultaneously reducing process development time. Pressure to reduce development costs and time, to improve manufacturing efficiency, and to control the costs of supply, will be significant and will likely become the differentiating factor for commercialisation. We will create the technologies, skill-sets and trained personnel needed to enable UK manufacturers to deliver the promise of advanced medical precision and patient screening. The Future Targeted Healthcare Manufacturing Hub and its research and translational spokes will network with industrial users to create and apply the necessary novel methods of process development and manufacture. Hub tools will transform supply chain economics for targeted healthcare, and novel manufacturing, formulation and control technologies for stratified and personalised medicines. The Hub will herald a shift in manufacturing practice, provide the engineering infrastructure needed for sustainable healthcare. The UK economy and Society Wellbeing will gain from enhanced international competitiveness.

Some radioactive molecules emit gamma radiation that can be detected outside the body and so when injected into humans and animals, in safe low levels, can be used to generate images, using sophisticated scanners, of the brain for biomedical research and clinical diagnosis. However, the molecules have to be designed to target the sites of the brain to be investigated, which is done by attaching a biological compound to the radioactive molecule to create products called radiopharmaceuticals. Due to the severe lack of scientists in the UK who have the specialised skills to design and prepare these radiopharmaceuticals we plan to recruit and train a scientist to join our multidisplicinary team. To achieve this we have created a bespoke training programme which will involve learning from researchers in academia and industry, who are either developing and/or using this imaging technology. As part of this training the scientist will help design new radiopharmaceuticals that would then be used in our on-going research programmes to understand the biological mechanisms of some major diseases and disorders of the brain, and thereby identify some possible treatments. For this specific programme we would be undertaking research projects on traumatic brain injury, depression, schizophrenia, obsessive compulsive disorder and drug addiction.

Chiral amines are prevalent in natural products, which often display potent biological activity. Such chiral amine motifs are also frequently found in pharmaceutical drug compounds and chemical building blocks meaning that the development of environmentally benign and sustainable routes to produce these important motifs is extremely desirable. Nature synthesizes these complex and valuable molecules through the action of highly specialized enzymes. These natural catalysts enable an extremely efficient biosynthesis from simple starting materials, installing functional groups with exceptional levels of selectivity. Chemical catalysts are frequently designed to mimic the action of enzymes and are often capable of achieving impressive selectivity. However, unlike enzymes, processes involving these catalysts usually involve high temperatures, sub-optimal pH, organic solvent and complex purification methods. Enzymes called omega-transaminases (TAs) catalyze the conversion of commercially available or easily accessible starting materials to high-value amines. These biocatalysts require an additional donor molecule to provide the amine functional group. This donor is ultimately converted to a by-product and the desired amine product is formed. However, the reaction is freely reversible and unless this by-product is removed from the reaction, low yields of the desired amine will be isolated, as the enzyme will more readily catalyse the reverse reaction to regenerate starting materials. A number of elegant approaches have been reported which remove this ketone by-product and allow access to appreciable quantities of the chiral amine. These strategies include the addition of expensive enzymes or the use of extremely large quantities of the amine donor in combination with the technically challenging removal of ketone by-products. One such approach, which relies on an extensively modified TA, is currently used for the industrial synthesis of the antidiabetic drug compound, sitagliptin. However, the approach is far from efficient and the development of this heavily modified TA biocatalyst was enormously challenging, highlighting an immediate need for more sustainable strategies for performing these biotransformations and for developing suitable enzyme catalysts. This research will build upon recent work reported in our laboratory that describes arguably the most efficient approach to date for performing biotransformations involving TAs. The success of the approach is due to spontaneous precipitation of the by-product, which cannot regenerate starting materials. This polymer is also highly colored and has allowed the development of an effective high-throughput screening strategy that enables the rapid identification of active enzymes. Our focus now is to optimize the process further and make it more suitable for industrial application. Specifically, low cost amine donor molecules will be used that are spontaneously removed from the reaction in a similar way to our previously reported method. We will also apply a simple high-throughput screening strategy to assist in the genetic engineering of natural enzymes in order to increase the scope of the reactions that they can catalyze and make them suitable for industrial scale synthesis. The enzymes developed in this study will enable cost-effective, sustainable and environmentally neutral methods for the small/medium and industrial scale production of one of the most important compound classes.

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.