The vision for Edinburgh's Centre for Mammalian Synthetic Biology (SynthSys-Mammalian) is to pioneer the development of the underpinning tools and technologies needed to implement engineering principles and realise the full potential of synthetic biology in mammalian systems. We have an ambitious plan to build in-house expertise in cell engineering tool generation, whole-cell modelling, computer-assisted design and construction of DNA and high-throughput phenotyping to enable synthetic biology in mammalian systems for multiple applications. In this way we will not only advance basic understanding of mammalian biology but also generate tools and technologies for near-term commercial exploitation in areas such as the pharmaceutical and drug testing industries, biosensing cell lines sensing disease biomarkers for diagnositics, novel therapeutics, production of protein based drugs e.g. antibodies and also programming stem cell development and differentiation for regenerative medicine applications. In parallel we will develop and implement new understanding of the social and economic impact of this far-reaching technology to ensure its benefits to society.

This proposal will deliver novel, integrated methodologies for the design and scalable manufacture of next generation resorbable polymer nanocomposites, linking the science and engineering principles which underpin successful processing of such materials. This will enable new smart health-care materials in applications from bone fracture fixation to drug delivery. The methodologies will be optimised on a system comprising novel nanoparticles, selected blends of medical-grade degradable polymer and specifically designed molecular dispersants. Optimised methodologies will be applied at scale on industrial equipment to produce demonstrator resorbable implants with specific structural attributes and degradation timescales. Wider applications include degradable food packaging and products requiring end-of-life disposal.

We live in a world surrounded by man-made materials that have been engineered to fulfill a specific purpose, from the many components of everyday articles such as razors and mobile phones to the high performance armour used to protect military personnel and the coatings applied to aircraft to mitigate the effects of lightning strikes. These achievements have been made possible through a profound understanding of the linkages between how a material is made, what structure it has (over a range of length scales), what properties result and how all of these factors ultimately determine the performance of the material in a specific application, be it for a few minutes or many tens of years. Often selecting the most suitable material, then designing its microstructure and processing it in a cost-effective and sustainable manner such that it is optimised for performance, is crucial to the 'enablement' of a new technology; conversely, failure to understand the vital role of materials can lead to missed business opportunities. Currently, there is a shortage of people with the required level of expertise in materials to meet the needs of UK industry. The Industrial Doctorate Centre in Micro- and NanoMaterials and Technologies (IDC in MiNMaT) aims to meet those needs by providing the UK with materials science and engineering doctoral graduates, with the combination of knowledge, translatable research expertise, interpersonal skills and confidence to enable them to tackle the most challenging materials problems and make a real impact on the performance and international presence of UK industry. This will be achieved by building on a foundation of international excellence in materials science and engineering, world-leading expertise in characterisation and a proven track record in delivering a highly regarded Engineering Doctorate (EngD) programme. This is a four-year research degree comprising a taught element and a research element, although within the MiNMaT IDC they are interwoven to form a coherent programme rather than being distinct parts. The research engineer (as the student is known) is based with their industrial sponsor, working on their research problems at their premises for the whole programme. Their focus is the solution of academically challenging and industrially relevant processing-microstructure-property-performance relationship problems. Taking place over all four years, carefully integrated intensive short courses (normally one week duration, at the University) form the taught component. These courses build on each other and augment the research. By using a core set of courses, graduates from a number of physical science/engineering disciplines can acquire the necessary background in materials. This capacity is essential as demand for materials scientists and engineers cannot be met without adding to the numbers of students who have studied materials at undergraduate level. Thus, the IDC in MiNMaT offers a solution to the UK's need for 'employment-ready', well-rounded graduates with excellent materials science and engineering research credentials.

The EPSRC Centre for Doctoral training in Materials for Demanding Environments will primarily address the Structural Integrity and Materials Behaviour priority area, and span into the Materials Technologies area. The CDT will target the oil & gas, aerospace and nuclear power industrial sectors, as well as the Defence sector. Research and training will be undertaken on metals and alloys, composites, coatings and ceramics and the focus will be on understanding the mechanisms of material degradation. The Centre will instil graduates with an understanding of structural integrity assessment methodologies with the aim to designing and manufacturing materials that last longer within a framework that enables safe lifetimes to be accurately predicted. A CDT is needed as the capability of current materials to withstand demanding environments is major constraint across a number of sectors; failure by corrosion alone is estimated to cost over $2.2 Trillion globally each year. Further understanding of the mechanisms of failure, and how these mechanisms interact with one another, would enable the safe and timely withdrawal of materials later in their life. New advanced materials and coatings, with quantifiable lifetimes, are integral to the UK's energy and manufacturing companies. Such technology will be vital in harvesting oil & gas safely from increasingly inaccessible reservoirs under high pressures, temperatures and sour environments. Novel, more cost-effective aero-engine materials are required to withstand extremely oxidative high temperature environments, leading to aircraft with increased fuel efficiency, reduced emissions, and longer maintenance cycles. New lightweight alloys, ceramics and composites could deliver fuel efficiency in the aerospace and automotive sectors, and benefit personal and vehicle armour for blast protection. In the nuclear sector, new light water power plants demand tolerance to neutron radiation for extended durations, and Generation IV plants will need to withstand high operating temperatures. It is vital to think beyond traditional disciplines, linking aspects of metallurgy, materials chemistry, non-destructive evaluation, computational modelling and environmental sciences. Research must involve not just the design and manufacturing of new materials, but the understanding of how to test and observe materials behaviour in demanding service environments, and to develop sophisticated models for materials performance and component lifetime assessment. The training must also include aspects of validation, risk assessment and sustainability.

Regenerative medicine aims to develop biomaterial and cell-based therapies that restore function to damaged tissues and organs. It is a cornerstone of contemporary and future medicine that needs a multidisciplinary approach. There is a world-wide shortage in scientists with such skillsets, which was highlighted in 2012 by the Research Councils UK in their 'A Strategy for UK Regenerative Medicine" which promotes 'training programmes to build capacity and provide the skills-base needed for the field to flourish'. The major clinical need for regenerative medicine was highlighted by the Science and Technology Committee (House of Lords; July 2013), who identified that 'The UK has the chance to be a leader in [regenerative medicine] and this opportunity must not be missed', and that 'there is likely to be a £44-54bn NHS funding gap by 2022 and that management of chronic disease accounts for around 75% of all UK health costs'. Vascular diseases are the leading cause of death and disability worldwide, musculoskeletal diseases have a huge burden in pain and disability, diabetes may be the 7th leading cause of death by 2030, and peripheral nerve injuries impair mobility after traumatic injuries. There is a pressing need for commercial input into regenerative medicine. Whilst the next generation of therapies, such as stem cells and biomaterials, will be underpinned by cutting-edge biology and bioengineering, strong industrial-academic partnerships are essential for developing and commercialising these advances for clinical benefit. We have established strong industrial partnerships which will both enhance the CDT training experience and provide major added value to our industrial partners. Regenerative medicine is a top priority for the University of Manchester (UoM) which has excellence in interdisciplinary graduate training and a critical mass of internationally renowned researchers, including newly appointed world-leaders. Our regenerative medicine encompasses physical, chemical, biological and medical sciences; we focus on tissue regeneration and inflammation, engineering and fabrication of biomaterials, and in vivo imaging and clinical translation, all on our integrated biomedical campus. We propose a timely Centre for Doctoral Training in Regenerative Medicine in Manchester that draws on our exceptional multidisciplinary depth and breadth, and directly addresses the skills shortage in non-clinical and clinical RM scientists. Our expertise integrates tissue regeneration & repair, the design & engineering of biomaterials, and the clinical translation of both biological and synthetic constructs. Our centres of excellence and internationally-leading supervisors across this multidisciplinary spectrum (details in Case for Support and UoM Letter of Support) highlight the strength of our scientific training environment. Defining CDT features will be: integrated cohort-based multidisciplinary training; skills training in engineering, biomedical sciences and pre-clinical translation; imaging in national Large Facilities; medical problem-solving nature of clinically co-supervised PhD projects, including in vivo training; comprehensive instruction in transferable skills and commercialisation; outward-facing ethos with placements with UK Regenerative Medicine Platform hub partners (UoM is partner on all three funded hubs), industrial partners, and international exchanges with world-class similarly-orientated doctoral schools; presentations in seminars and conferences. In this way, we will deliver a cadre of multidisciplinary scientists to meet the needs of academia and industry, and ensure the UK's continuing international leadership in RM. Ultimately, through training this cadre of doctoral scientists in regenerative medicine, we will be able to improve wound healing, repair injured nerves, blood vessels, tendon and ligaments, treat joint disease and restore function to organs damaged by disease.