Analysis of molecular and cellular events is crucial in modern life sciences research, for a better understanding of (i) fundamental biological processes, (ii) the changes that characterise associated disease states, and (iii) the development of therapeutics. This research proposal brings together seven research areas, spanning the regulation of the immune and nervous systems, haemopoiesis, tissue development and regeneration and cell metabolism that share a common theme of wanting to utilise sensitive, quantitative and high throughput state-of-the-art instrumentation to analyse a range of cellular mechanisms. This instrument is the Mesoscale Discovery (MSD) SECTOR Imager (SI) 6000 which offers a sensitive, adaptable platform with which to measure several analytes in cell or cell-derived samples. The technology relies on the use of chemically tagged antibodies that recognize the analytes of choice. When bound to their target, the Abs emit light upon electrochemical stimulation which is measured and quantified. The main features provided by the instrument are: - the ability to accurately quantify activation of specific signals; - it facilitates detection of multiple signals simultaneously. - in situations where cell samples may be limiting, information on several different signalling molecules can be generated simultaneously. - the system allows for more rapid analysis, - provides platform for developing our own custom made assays for future applications.

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.

The WHO has recently announced its commitment to end cervical cancer as a public health problem globally. Cervical cancer is the commonest cancer among women aged between 15 and 44 years in East Africa and is the leading cause of cancer-related mortality. It is caused by infection with human papillomavirus (HPV), a sexually transmitted virus. Infection with HPV can also cause other diseases such as genital warts, which affect both men and women. In high income countries, cervical cancer is prevented by vaccinating girls against HPV infection before they start having sex and screening sexually active women for HPV infection and/or cervical abnormalities. However, in many countries in Africa and other parts of the world, many women still die of the disease because screening programmes are absent or limited, and vaccination is only just starting to be rolled out. In Tanzania, which has one of the highest rates of cervical cancer in the world, HPV vaccines were introduced to 14-year-old girls in 2018. Evidence suggests that setting up and sustaining an HPV vaccination programme for young girls requires considerable investment in human and financial resources. These new programmes are finding it challenging to deliver the vaccines to most girls who should be receiving them. This will make it difficult to eliminate cervical cancer as HPV will still be able to spread in young people. Scientists therefore need to explore novel ways to deliver the vaccine to prevent infection to those who are not vaccinated. If enough people receive the HPV vaccine, then their unvaccinated sexual partners can also be protected. This has been shown in countries like Australia and Scotland, where vaccination of girls resulted in a decline in rates of HPV-related diseases in boys as well as girls. Given the challenges in getting enough girls vaccinated in many countries, one approach to controlling cervical cancer by preventing infection in unvaccinated girls is to offer the vaccine to their potential male sexual partners (known as gender-neutral vaccination). We propose to conduct a trial to test this strategy in Tanzania. We will see if we can reduce the amount of HPV infection present in communities by vaccinating of boys alongside vaccination of girls. We will do this using a single dose of HPV vaccine in boys, which may be sufficiently protective to prevent infection in boys and also prevent spread of HPV to unvaccinated girls. We will conduct a study called a cluster-randomised trial among communities in Tanzania (where each community is a cluster). In 2020, we will start by doing a baseline survey in 26 communities to determine how many boys and girls aged 16-22 years have HPV infection. We will then randomly select 13 communities where boys aged 14-18 years will be given HPV vaccine alongside the routine female HPV vaccination that is being given by the Tanzanian government. Three years after offering boys the vaccination, we will go back into the communities and do another survey to determine how many boys and girls aged 16-22 years-old have HPV infection. We will then be able to show whether the proportion of people infected with HPV differs between the communities that did and did not have male vaccination. At the same time, we will also be able to measure the impact of the girls-only vaccination on HPV infection by comparing the proportion of 16-22-year-old girls infected with HPV in the female-only vaccination communities at baseline and 3 years later. In our study, we will also follow up 200 vaccinated boys in order to check their immune responses to the vaccine, and we will do interviews in the communities to explore people's views about offering boys vaccination. We will also look at the cost of adding in vaccination of boys to the programme. This work will be extremely important in informing future HPV vaccination strategies and will be the first randomised trial of gender-neutral vaccination in Africa.

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.