The lifETIME CDT will focus on the development of non-animal technologies (NATs) for use in drug development, toxicology and regenerative medicine. The industrial life sciences sector accounts for 22% of all business R&D spend and generates £64B turnover within the UK with growth expected at 10% pa over the next decade. Analysis from multiple sources [1,2] have highlighted the limitations imposed on the sector by skills shortages, particularly in the engineering and physical sciences area. Our success in attracting pay-in partners to invest in training of the skills to deliver next-generation drug development, toxicology and regenerative medicine (advanced therapeutic medicine product, ATMP) solutions in the form of NATs demonstrates UK need in this growth area. The CDT is timely as it is not just the science that needs to be developed, but the whole NAT ecosystem - science, manufacture, regulation, policy and communication. Thus, the CDT model of producing a connected community of skilled field leaders is required to facilitate UK economic growth in the sector. Our stakeholder partners and industry club have agreed to help us deliver the training needed to achieve our goals. Their willingness, again, demonstrates the need for our graduates in the sector. This CDT's training will address all aspects of priority area 7 - 'Engineering for the Bioeconomy'. Specifically, we will: (1) Deliver training that is developed in collaboration with and is relevant to industry. - We align to the needs of the sector by working with our industrial partners from the biomaterials, cell manufacture, contract research organisation and Pharma sectors. (2) Facilitate multidisciplinary engineering and physical sciences training to enable students to exploit the emerging opportunities. - We build in multidisciplinarity through our supervisor pool who have backgrounds ranging from bioengineering, cell engineering, on-chip technology, physics, electronic engineering, -omic technologies, life sciences, clinical sciences, regenerative medicine and manufacturing; the cohort community will share this multidisciplinarity. Each student will have a physical science, a biomedical science and a stakeholder supervisor, again reinforcing multidisciplinarity. (3) Address key challenges associated with medicines manufacturing. - We will address medicines manufacturing challenges through stakeholder involvement from Pharma and CROs active in drug screening including Astra Zeneca, Charles River Laboratories, Cyprotex, LGC, Nissan Chemical, Reprocell, Sygnature Discovery and Tianjin. (4) Embed creative approaches to product scale-up and process development. - We will embed these approaches through close working with partners including the Centre for Process Innovation, the Cell and Gene Therapy Catapult and industrial partners delivering NATs to the marketplace e.g. Cytochroma, InSphero and OxSyBio. (5) Ensure students develop an understanding of responsible research and innovation (RRI), data issues, health economics, regulatory issues, and user-engagement strategies. - To ensure students develop an understanding of RRI, data issues, economics, regulatory issues and user-engagement strategies we have developed our professional skills training with the Entrepreneur Business School to deliver economics and entrepreneurship, use of TERRAIN for RRI, links to NC3Rs, SNBTS and MHRA to help with regulation training and involvement of the stakeholder partners as a whole to help with user-engagement. The statistics produced by Pharma, UKRI and industry, along with our stakeholder willingness to engage with the CDT provides ample proof of need in the sector for highly skilled graduates. Our training has been tailored to deliver these graduates and build an inclusive, cohesive community with well-developed science, professional and RRI skills. [1] https://goo.gl/qNMTTD [2] https://goo.gl/J9u9eQ

The bone marrow is a site of health and disease. In health, it produces all of the blood cells that we rely on to carry oxygen and protect us from infection. However, the stem cells that produce the blood and that reside in the marrow, the haematopoietic stem cells (HSCs), age and can tip over into disease states, such as developing leukaemia. Factors such as smoking and treatment of cancers elsewhere in the body (toxic effects of chemotherapy/radiotherapy) can accelerate ageing, and therefore, drive the transition to disease. Further, it forms a home to other cancer cells, that leave their original tumour and move, or metastasise, to the bone marrow. Once in the marrow, they can become dormant, hiding from chemotherapies and activating sometime later to form devastating bone cancers. The cues that wake cancer cells from dormancy are largely unknown. If models of the bone marrow that contain human cells and that can mimic key facets of the niche in the lab, such as blood regeneration, cancer evolution and dormancy, can be developed it would be a big help in the search for better cancer therapies. We are developing the materials and technologies required to meet this challenge. In this programme of research, we will tackle three biomedical challenges: 1) HSC regeneration. Bone marrow transplantation (more correctly HSC transplantation) is a one-donor, one-recipient therapy that can be curative for blood diseases such as leukaemia. It is limited as HSCs cannot be looked after well out of the body. Approaches to properly look after these precious cells in the lab could allow this key therapy to become a one-donor, multiple recipient treatment. Further, the ability to look after the cells in the lab would open up the potential for genetically modifying the cells to allow us to cure the cells and put them back into the patient, losing the need for patient immunosuppression. 2) Cancer evolution. As we get older, our cells collect mutations in their DNA and these mutations can be drivers of cancer. Lifestyle choices such as smoking, and side effects of treatments of other diseases can also add mutations to the cells. As blood cancers develop, the bone marrow changes its architecture to protect these diseased HSCs. Our 3D environments will allow us to better understand this marrow remodelling process and how drugs can target cancers in this more protective environment. The models will also allow us to study the potential toxicity of gene-edited HSCs to make sure they don't produce unwanted side effects or are not cancerous in themselves. 3) Dormancy. What triggers dormancy and activation from dormancy are poorly understood. By placing our 3D environments in a miniaturised format where we can connect other models that include infection and immune response, we can start to understand the factors involved in the activation of cancer cells from dormancy. Our vision is driven by materials and engineering, as the bone marrow niche is rich in structural and signalling biological materials (proteins). Therefore, we will establish three engineering challenges: (1) Cells can be controlled by the stiffness and viscous nature of materials (viscoelasticity). We will therefore develop synthetic-biological hybrid materials that can be manufactured to have reproducible physical properties and that have biological functionality. (2) We will develop these materials to interact with growth factors and bioactive metabolites, both of which are powerful controllers of cell behaviours. These materials will be used to assemble the HSC microenvironments in lab-on-chip (miniaturised) format to allow high-content drug and toxicity screening. (3) We will develop real-time systems to detect changes in cell behaviour, such as the transition from health to cancer using Raman and Brillouin microscopies. The use of animals in research provides poor predictivity. We will offer better than animal model alternatives.

Advanced economies are now confronted with a serious challenge that requires us to approach problem solving in a completely different way. As our global population continues to rise we must all consider several quite taxing philosophical questions, most pressingly we must address our addiction to economic growth, our expectation for longer, healthier lives and our insatiable need to collect more stuff! Societies demand for performance molecules, ranging from pharmaceuticals to fragrances or adhesives to lubricants, is growing year-on-year and the advent of competition in a globalised market place is generally forcing the market price downward, cutting margins and reducing the ability for some industry sectors to innovate. Atoms to Products (A2P) is an exciting opportunity to forge a new philosophy that could underpin the next phase of sustainable growth for the chemicals manufacturing industry in the UK and further afield. An overarching driving force in the development of A2P was the desire to apply the knowledge and learning of Green and Sustainable Chemistry to the creative phases embedded in the discovery and development of performance molecules that deliver function in applications as diverse as pharmaceuticals, agrochemicals and food. We propose a multi-disciplinary CDT in sustainable chemistry which aims to achieve a sustainable pipeline of performance molecules from design-to-delivery. A2P will create an Integrated Approach to Sustainable Chemistry, promoting a culture of waste minimisation, emphasising the development of a circular economy in terms of materials and matter replacing current modes of consumption and resource use. A2P represents a multidisciplinary group of 40 academic advisors spanning 7 academic disciplines, working together with a growing family of industrial partners spanning well-known multinationals including Unilever, GSK, AstraZeneca and Croda, and niche SMEs, including Promethean Particles, Sygnature and European Thermodynamics. Interestingly all partners have expressed a common desire to develop Smarter products using Better chemistry to enable Faster processing and Shorter manufacturing routes. A2P will drive innovation by: 1 fostering a multidisciplinary, cohort based approach to problem solving; 2 focussing on challenge areas identified by our A2P partners such that sub-groups of our cohort can become immersed in research at the "coal-face"; 3 embedding aspects of data-driven decision making in the day-to-day design and execution of high quality research either on paper or indeed in the lab; 4 nurturing a vibrant and supportive community that allows PhD candidates to think 'outside of the box' in a relatively risk- free way; 5 empowering the development of 'next generation' synthetic methods to drive efficiency, selectivity and productivity, underpinned my molecular modelling and the use of machine learning to extract additional value from experimental data; 6 developing sustainable processes that deliver efficiency and transition to scale-up from g to Kg, under-utilised approaches, including electrochemistry, will be investigated increase atom efficiency and reduce reliance on precious metals; 7 enabling efficient scale-up of new processes using flow-chemistry and 3-D printing technology to "print" the most efficient reactor system, thereby maximising throughput whilst efficiently managing mass transport and thermal factors; 8 applying robust reaction/process evaluation metrics such that comparative advantages can be quantified, providing evidence for real process decision making. Integration of outcomes from all A2P PhD projects, in combination with the expertise of all A2P partners, will deliver a major contribution to the health of the UK chemicals manufacturing industry. A2P will provide mentorship and training to the next generation of leaders securing innovation and future growth for this critical manufacturing sector.

Sustainability is the crucial factor in the future of the UK's chemistry-using industries with all companies sharing the vision of lower carbon footprints and reduced use of precious resources. However this sustainability can only be achieved if industry can recruit the right people. This CDT addresses the shortage of PhD graduates who have the skills needed to implement sustainable technologies. We will provide co-ordinated interdisciplinary training to produce a new generation of innovative PhD scientists and engineers with the skills needed by industry. Using the strong collaboration between Chemistry and Engineering at Nottingham as a springboard, we will launch a much wider integrated partnership involving chemistry, engineering, food science, and business to create more sustainable processes and compounds for the chemistry-using industries. This approach is strongly endorsed by our industrial partnerships, developed over many years, including companies from the major chemistry-using sectors. The demand for chemistry knowledge, skills, technologies and training will grow dramatically in the period 2015-2030 to meet the global challenges of healthcare and better medicines for an ageing population, safer agrochemicals to aid food production for an increasing population, and the need for ever smarter advanced materials for new and energy efficient technologies. However, chemical manufacturing is demanding in terms of use of energy and natural resources, as well as its impact on the environment, and consumes far more resource than is sustainable. Hence there is a need to develop new chemical and manufacturing solutions that are safe, efficient and, above all, sustainable. Sustainability is the issue facing the entire global chemicals industry, and our vision is to train a new generation of scientists to find innovative "green" resource and energy efficient solutions that have the lowest possible environmental impact, demonstrate social responsibility, and make a positive contribution to economic growth. Our proposed EPSRC Centre for Doctoral Training (CDT) in Sustainable Chemistry at Nottingham, will be highly interdisciplinary. It will not only capitalise on the strong links between Chemistry and Engineering, but will also reach into the Biosciences, Food Science and the Business School. The CDT builds upon our international track record in green chemistry, and will develop Nottingham's unique combination of skills and technologies in synthetic methodology, green chemistry, materials science, biotransformations, microwave technologies, food science, supply chains and business development, combined with high level commercial input through our very significant industrial involvement. Our CDT will provide world class training and our PhD graduates will have a full understanding of the sustainability impact of their work, with consideration for its wider environmental, societal and economic benefits. Our training framework, will produce "industry ready" PhDs who will have an excellent understanding of sustainability for the chemicals sector. These industries are well aware of the major issues, and they need new solutions and a new generation of trained researcher to deliver those solutions. By engaging with industry from an early stage, the CDT will deliver PhD training that addresses these concerns. The CDT will be based in an iconic new building, the UK's first Carbon Neutral Laboratory. This unique facility will provide a sustainable and energy efficient working environment that we hope will help inspire, motivate and ultimately deliver PhD graduates with a much better set of skills to minimise environmental impact and build sustainability into their work. The CDT will also serve as a global hub to visiting researchers wishing to develop expertise in sustainable chemistry, and to engage the public through Nottingham's unrivalled outreach activities such as the The Periodic Table of Videos.