Infectious diseases come at a huge societal and economical cost. This has recently been shown by the COVID-19 pandemic. Looking forward, arguably the largest threat is antimicrobial resistance (AMR). As pathogens develop resistance against currently available antimicrobials (e.g., antibiotics) and as the development of new antimicrobials has stalled, we are risking an estimated 10M deaths per year globally and a US$100 trillion costs to the world economy by 2050. We here propose a Centre for Doctoral Training on Engineering Solutions for Antimicrobial Resistance, with the overall aim of training physical scientists and engineers with the specialist research skills as well as broad contextual skills to create rapid impact targeting the AMR challenge. This includes different disciplines and wider aspects such as commercialisation/translation, public-health context, regulation and standardisation, implementation and adoption, public awareness and perception, and communication. Identifying key research areas that depend on cutting-edge research advances in engineering and physical sciences, our Centre for Doctoral Training focuses on preventing the spread of infection, on surveillance and diagnostics, and on antimicrobial and vaccine development. By designing and delivering our training programme with public health institutions, multinational businesses, SMEs and charities, we maximise the impact of such research on addressing the public health threat of AMR and on exploiting business opportunities that are also associated with solutions to it.

Biotechnology firms in the UK increasingly access funds from financial markets, such as the Alternative Investment Market (AIM), rather than traditional venture capital (VC) firms because they are dissatisfied with the poor advice and lack of funding support from traditional VCs. In addition, many of these firms have adopted innovative business models that speed up product development processes by using highly experienced boards of directors and advisors to access external knowledge. Because previous research has focused on funding from venture capitalists, at present little is known about what sorts of business models are most appropriate for this new form of funding and how these boards and advisors are motivated by new forms of financing. This research seeks to (a) understand how these changes impact firm performance and (b) develop innovative management tools to help firms set up a powerful board, and show how that board should operate and how it should access AIM, other non-VC sources of money, and specialist advisors.Previous research on biotechnology start-ups typically draws on a model extrapolated from US experience in the 1980s, where the stages of firm development are linked to types of funding: seed funding (including university technology funds); business angels; V-C (venture capital) followed by IPO (initial public offering on financial markets) or trade sales. While the model may have once been useful, it is increasingly inappropriate for the UK as some firms are short-circuiting stages of the cycle, while others are developing alternative routes. The fact that AIM is now larger than VC as a total supply of finance to UK technology in general and to biotechnology in particular emphasises how the UK has moved towards a distinctive market-based biotechnology funding model.Under this new model, university spin-outs and other start-up firms exploit strong intellectual property over their technology to go straight from founding to forming a highly-skilled board of directors. These boards develop credentials impressive enough for a medium sized public-listed-company very early and are used to access levels of external, specialist professional knowledge normally associated with well established firms. Firms adopting this model rely much more heavily on high powered boards and specialists for managerial advice (rather than VCs and university technology transfer offices). It has been assumed that this knowledge outsourcing strategy could not work as start-up firms lack the resources to attract such high-level advisors. However, preparatory research and first hand experience (one of the proposers is on several biotechnology boards) suggests that the practice is increasingly important. The two strands of research within the project - funding innovations and new managerial knowledge arrangements - are closely connected. It seems clear that using high-powered boards and high levels of external advisors makes a young firm more attractive for floatation on public markets, enabling them to draw on much larger sources of funding. While the opportunity to be involved in public visible, fast growth firms attracts the high-powered boards in the first place. By better understanding these changes, and developing management tools to assit firms this project will asssit the development of high-tech biotech firms within the UK economy and extend the application of innovative forms of financing.

Synthetic Biology is a growing field of science that combines Biosciences, Chemistry, Physics, Information Technology and Engineering, and involves the redesigning end engineering of organisms for functional purposes, for example to produce valuable substances (e.g. medicines) or gain new functions (e.g. sensing and responding to something in the environment). Synthetic Biology aspires to tackle grand challenges surpassing what is possible through traditional technologies: it has wide-ranging applications in healthcare, environmental protection, energy, agriculture, computing, advanced chemicals and materials. Synthetic Biology has grown significantly in the UK over the past decade, thanks to a >£400M investment via the Synthetic Biology for Growth Programme. One of the key investments has been the SynBioCDT: the first UK CDT in Synthetic Biology funded in 2014 by the EPSRC and BBSRC and run by the Universities of Oxford, Bristol and Warwick. The SynBioCDT trained 79 excellent PhD students selected from >650 applicants, and attracted support from industrial, academic and public-facing partners. Our graduate students have gone on to work within the bioeconomy and have established disruptive start-ups. The term "Engineering Biology" has been recently adopted to highlight the essential transition of Synthetic Biology into a mature Engineering discipline. The recent UKRI National Engineering Biology Programme (NEBP) sets the UK ambition for the field and encompasses the capabilities that can support the exploitation of Engineering Biology for economic and public benefit. The Universities of Bristol and Oxford aim to establish a new CDT in Engineering Biology, the EngBioCDT, to train the academic and industrial Engineering Biology leaders of tomorrow, and to equip them with skills needed to contribute toward scalable, robust, and transformative engineering of biomimetic and biological systems. The EngBioCDT builds on our experience with the SynBioCDT and will address the NEBP requirement for a new generation of biological engineers able to translate cutting-edge science into real-world impact; it will support the EPSRC focus area 'Frontiers in Engineering and Technology'. The EngBioCDT will enable cohesive cohorts of students to gain expertise in the design, modelling and engineering of biological components and systems; to understand broad concepts ranging from biomolecular interactions to cell function; and to augment the Engineering Biology approach with robotics, automation and AI. Students will obtain advanced skills in programming and engineering; implement biological design across scales; place research in the context of both basic and applied science; and become cognisant of challenges such as process development and scale-up in biotechnology. Students will undertake both group and individual projects before starting their doctoral project. The EngBioCDT will take advantage of the expertise provided by the two Universities and our industrial partners, which will all be catalysts for inter-University and inter-sector training and research. Students will also have superb opportunities to engage with leading international academics, for example through an annual Summer School, and by participating in international conferences and workshops. The environment is exceptional. Bristol hosted BrisSynBio, one of six UKRI-funded Synthetic Biology Research Centres, and now hosts the Bristol BioDesign Institute and the Bristol Centre for Engineering Biology; the CDT Director is a EPSRC Fellow. Oxford, which led the SynBioCDT, received three fellowships and a programme grant in Engineering Biology, and offers vibrant translational opportunities. The applicants provide expertise in graduate training and many of them have previously worked together effectively. Our pool of >70 supervisors reflects the truly multidisciplinary nature of Engineering Biology, and includes internationally renowned researchers.

The Covid-19 pandemic continues to take a huge toll - an estimated 6.3m people have died including 178,000 in the UK. Globally 1.6bn students have missed school, 250m people will be pushed into extreme poverty and economic losses are estimated at £12tr. History shows that epidemic and pandemic threats constantly emerge, whilst SARS-CoV-2 continues to mutate as it becomes endemic. It is clear that major losses could be prevented by sustained domestic investment in public health. Work undertaken within Vax-Hub1 on responsive technologies and accelerated quality control methods enabled rapid development and manufacture of the ChAdOx1 vectored vaccine against SARS-CoV-2 (licensed for emergency use in December 2020 via a non-profit partnership with AstraZeneca). Over 2.9bn doses have now been released in 180 countries. The UK had a leading role during the pandemic and the proposed Hub builds on this success to advance novel research on a broader range of technologies. Working closely with stakeholders, Vax-Hub will enable the UK to be better prepared for the next pandemic. This investment into The Future Vaccine Manufacturing Hub will enable our vision to make the UK the global centre for vaccine discovery, development and manufacture. The Vaccine Manufacturing Hub brings together a world-class multidisciplinary team with decades of cumulative experience in all aspects of vaccine design and manufacturing research. This Hub will bring academia, industry, not-for-profit organizations and policy makers together to propose radical change in vaccine development and manufacturing technologies, building on a technological innovation culture. The Hub will enhance future vaccine manufacturing through (i) de-risked manufacture of new vaccines by strategically innovating for a selected range of the most promising platform technologies (established and novel/disruptive); (ii) developing manufacturing options that improve the product quality and so immunogenicity; (iii) streamlined manufacturing process development with novel responsive solutions and advanced digitalisation strategies; (iii) a focus on enhancing stability and needle-free administration routes so they become a reality within the lifetime of the Hub. The proposed Hub would be the natural location for early-stage research before projects are transferred to a GMP manufacturing facility. The work focuses on development of improved vaccine platforms which can be flexible enough to be used for multiple product manufacture. These improved vaccine technologies are used as case studies to test rapid and responsive development tools to create a whole process mimicking vaccine manufacture, which could be easily and quickly deployed in case of epidemic/pandemic scenario. Finally the research focuses on standard and novel adjuvants to make mucosal delivery a reality, thus allowing alternative route to injection for mass administration. The Hub will establish the UK as the global centre for end-to-end vaccine research and manufacture. Additionally, vaccines should be considered a national security priority, as it is evident that diseases do not respect international boundaries, thus this work into capacity building and rapid response is a significant advantage. The impact of this Hub will be felt internationally, as the UK reaffirms its leadership in Global Health and works to ensure that the outputs of this Hub reach the global community and the most vulnerable, especially children.

Vaccines are the most successful public health initiative of the 20th century. They save millions of lives annually, add billions to the global economy and extended life expectancy by an average of 30 years. Even so, the UN estimates that globally 6 million children each year die before their 5th birthday. While vaccines do exist to prevent these deaths, it is limitations in manufacturing capacity, technology, costs and logistics that prevent us for reaching the most vulnerable. The UK is a world leader in vaccine research and has played a significant leadership role in several public health emergencies, most notably the Swine Flu pandemic in 2009 and the recent Ebola outbreak in West Africa. While major investment has been made into early vaccine discovery - this has not been matched in the manufacturing sciences or capacity. Consequently, leading UK scientists are forced to turn overseas to commercialise their products. Therefore, this investment into The Future Vaccine Manufacturing Hub will enable our vision to make the UK the global centre for vaccine discovery, development and manufacture. We will create a vaccine manufacturing hub that brings together a world-class multidisciplinary team with decades of cumulative experience in all aspects of vaccine design and manufacturing research. This Hub will bring academia, industry and policy makers together to propose radical change in vaccine development and manufacturing technologies, such that the outputs are suitable for Low and Middle Income Countries. The vaccine manufacturing challenges faced by the industry are to (i) decrease time to market, (ii) guarantee long lasting supply - especially of older, legacy vaccine, (iii) reduce the risk of failure in moving between different vaccine types, scales of manufacture and locations, (iv) mitigating costs and (v) responding to threats and future epidemics or pandemics. This work is further complicated as there is no generic vaccine type or manufacturing approach suitable for all diseases and scenarios. Therefore this manufacturing Hub will research generic tools and technologies that are widely applicable to a range of existing and future vaccines. The work will focus on two main research themes (A) Tools and Technologies to de-risk scale-up and enable rapid response, and (B) Economic and Operational Tools for uninterrupted, low cost supply of vaccines. The first research theme seeks to create devices that can predict if a vaccine can be scaled-up for commercial manufacture before committing resources for development. It will include funds to study highly efficient purification systems, to drive costs down and use genetic tools to increase vaccine titres. Work in novel thermo-stable formulations will minimise vaccine wastage and ensure that vaccines survive the distribution chain. The second research theme will aim to demystify the economics of vaccine development and distribution and allow the identification of critical cost bottlenecks to drive research priorities. It will also assess the impact of the advances made in the first research theme to ensure that the final cost of the vaccine is suitable for the developing world. The Hub will be a boon for the UK, as this research into generic tools and technologies will be applicable for medical products intended for the UK and ensure that prices remain accessible for the NHS. It will establish the UK as the international centre for end-to-end vaccine research and manufacture. Additionally, vaccines should be considered a national security priority, as diseases do not respect international boundaries, thus this work into capacity building and rapid response is a significant advantage. The impact of this Hub will be felt internationally, as the UK reaffirms its leadership in Global Health and works to ensure that the outputs of this Hub reach the most vulnerable, especially children.