This Centre for Doctoral training in Industrially Focused Mathematical Modelling will train the next generation of applied mathematicians to fill critical roles in industry and academia. Complex industrial problems can often be addressed, understood, and mitigated by applying modern quantitative methods. To effectively and efficiently apply these techniques requires talented mathematicians with well-practised problem-solving skills. They need to have a very strong grasp of the mathematical approaches that might need to be brought to bear, have a breadth of understanding of how to convert complex practical problems into relevant abstract mathematical forms, have knowledge and skills to solve the resulting mathematical problems efficiently and accurately, and have a wide experience of how to communicate and interact in a multidisciplinary environment. This CDT has been designed by academics in close collaboration with industrialists from many different sectors. Our 35 current CDT industrial partners cover the sectors of: consumer products (Sharp), defence (Selex, Thales), communications (BT, Vodafone), energy (Amec, BP, Camlin, Culham, DuPont, GE Energy, Infineum, Schlumberger x2, VerdErg), filtration (Pall Corp), finance (HSBC, Lloyds TSB), food and beverage (Nestle, Mondelez), healthcare (e-therapeutics, Lein Applied Diagnostics, Oxford Instruments, Siemens, Solitonik), manufacturing (Elkem, Saint Gobain), retail (dunnhumby), and software (Amazon, cd-adapco, IBM, NAG, NVIDIA), along with two consultancy companies (PA Consulting, Tessella) and we are in active discussion with other companies to grow our partner base. Our partners have five key roles: (i) they help guide and steer the centre by participating in an Industrial Engagement Committee, (ii) they deliver a substantial elements of the training and provide a broad exposure for the cohorts, (iii) they provide current challenges for our students to tackle for their doctoral research, iv) they give a very wide experience and perspective of possible applications and sectors thereby making the students highly flexible and extremely attractive to employers, and v) they provide significant funding for the CDT activities. Each cohort will learn how to apply appropriate mathematical techniques to a wide range of industrial problems in a highly interactive environment. In year one, the students will be trained in mathematical skills spanning continuum and discrete modelling, and scientific computing, closely integrated with practical applications and problem solving. The experience of addressing industrial problems and understanding their context will be further enhanced by periods where our partners will deliver a broad range of relevant material. Students will undertake two industrially focused mini-projects, one from an academic perspective and the other immersed in a partner organisation. Each student will then embark on their doctoral research project which will allow them to hone their skills and techniques while tackling a practical industrial challenge. The resulting doctoral students will be highly sought after; by industry for their flexible and quantitative abilities that will help them gain a competitive edge, and by universities to allow cutting-edge mathematical research to be motivated by practical problems and be readily exploitable.

Live viral vaccines and therapeutics are growing in popularity due to their high specific potency yet their manufacture remains hampered by poor recoveries of viral infectivity following concentration and purification. In particular, practitioners highlight two such difficulties; the poor recovery of infectious virus following sterile filtration and the search for high yielding purification techniques. These related problems derive primarily from viral inactivation by fluid shear and interfacial phenomenon in the membrane modules and chromatography equipment commonly used by industry. We seek to understand the mechanisms of viral inactivation in order to design new processing systems that provide higher recoveries and are simple to use. Experiments will be conducted to characterise the key morphological and functional characteristics of representative enveloped and non-enveloped viruses (using Ad5 and MoMULV) following exposure to well characterised fluid shear typical of of that encountered during sterile filtration and chromatography. Measurement of viral infectivity will be made (TCID50) and electron microscopy, immunogold labelling and real time PCR will be used to assess the influence of shear on the external viral proteins that mediate infectivity. All these analytical techniques are available in the academic partner's laboratory where the general approach has been previously shown valuable for the study of viral inactivation during lyophilisation. The effect of stabilising excipients and rheology modifying agents will be examined . CFD data on shear distributions in commercial filter housings will be obtained to guide these studies. Sterile filtration yields will be assessed for prototype membranes with a range of porosities, morphologies and surface properties in order to assess the influenec of membrane characteristics upon viral inactivation. The distribution of representative nanoparticles on membranes will be studied using fluorescent labelled HSA particles and confocal imaging. As a result, housing designs will be modified to reduce any maldistribution of viruses. Prototype filter assemblies will be similarly probed with fluorescent immuno-labelled viruses and confocal microscopy. From these studies improved sterile filtration equipment and procedures will result. Complete prototype disposable virus manufacturing systems will be fabricated using collections of commercially available units. Typically, cell culture in disposable bioreactors, including Wave, will be linked by adsorptive and size based membrane processing cartridges and the manufacturing performances of these systems will be characterised for the test viruses. The academic partner is familiar with such approaches, having previously adopted similar approaches for the manufacture of antibody based snake antivenoms in a BBSRC sponsored project. The industrial partner is a market leader in filtration and separations and has relevant process separation technologies for exploitation in this area. Limitations in processing capability will be identified using existing systems and new systems designed to provide improved performance. We anticipate that radical improvements will emerge from the re-designed cartridge housings that result from data obtained on the influence of fluid shear on infectivity. We expect too that the understanding of interfacial phenomena together with new materials that are emerging from the laboratories of the industrial partner will enable significantly higher viral recoveries to be achieved.

This proposal bids for £4.5M to both evolve and renew the Loughborough, Nottingham and Keele EPSRC CDT in Regenerative Medicine. The proposal falls within the 'Healthcare Technologies' theme and 'Regenerative Medicine' priority of the EPSRC call. This unique CDT is fully integrated across three leading UK Universities with complementary research profiles and a long track record of successful collaboration delivering fundamental and translational research. Cohorts of students will be trained in the core scientific, transferable, and translational skills needed to work in this emerging healthcare industry. Students will be engaged in strategic and high quality research programmes designed to address the major clinical and industrial challenges in the field. The CDT will deliver the necessary people and enabling technologies for the UK to continue to lead in this emerging worldwide industry.The multidisciplinary nature of Regenerative Medicine is fully captured in our proposal combining engineering, biology and healthcare thereby spanning the remits of the BBSRC and MRC, in addition to meeting EPSRC's priority area.

Aerosol science, the study of airborne particles from the nanometre to the millimetre scale, has been increasingly in the public consciousness in recent years, particularly due to the role played by aerosols in the transmission of COVID-19. Vaccines and medications for treating lung and systemic diseases can be delivered by aerosol inhalation, and aerosols are widely used in agricultural and consumer products. Aerosols are a key mediator of poor air quality and respiratory and cardiac health outcomes. Improving human health depends on insights from aerosol science on emission sources and transport, supported by standardised metrology. Similar challenges exist for understanding climate, with aerosol radiative forcing remaining uncertain. Furthermore, aerosol routes to the engineering and manufacture of new materials can provide greener, more sustainable alternatives to conventional approaches and offer routes to new high-performance materials that can sequester carbon dioxide. The physical science underpinning the diverse areas in which aerosols play a role is rarely taught at undergraduate level and the training of postgraduate research students (PGRs) has been fragmentary. This is a consequence of the challenges of fostering the intellectual agility demanded of a multidisciplinary subject in the context of any single academic discipline. To begin to address these challenges, we established the EPSRC Centre for Doctoral Training in Aerosol Science in 2019 (CDT2019). CDT2019 has trained 92 PGRs with 40% undertaking industry co-funded research projects, leveraged £7.9M from partners and universities based on an EPSRC investment of £6.9M, and broadened access to our unique training environment to over 400 partner employees and aligned students. CDT2019 revealed strong industrial and governmental demand for researchers in aerosol science. Our vision for CDT2024 is to deliver a CDT that 'meets user needs' and expands the reach and impact of our training and research in the cross-cutting EPSRC theme of Physical and Mathematical Sciences, specifically in areas where aerosol science is key. The Centre brings together an academic team from the Universities of Bristol (the hub), Bath, Birmingham, Cambridge, Hertfordshire, Manchester, Surrey and Imperial College London spanning science, engineering, medical, and health faculties. We will assemble a multidisciplinary team of supervisors with expertise in chemistry, physics, chemical and mechanical engineering, life and medical sciences, and environmental sciences, providing the broad perspective necessary to equip PGRs to address the challenges in aerosol science that fall at the boundaries between these disciplines. To meet user needs, we will devise and adopt an innovative Open CDT model. We will build on our collaboration of institutions and 80 industrial, public and third sector partners, working with affiliated academics and learned societies to widen global access to our training and catalyse transformative research, establishing the CDT as the leading global centre for excellence in aerosol science. Broadly, we will: (1) Train over 90 PGRs in the physical science of aerosols equipping 5 cohorts of graduates with the professional agility to tackle the technical challenges our partners are addressing; (2) Provide opportunities for Continuing Professional Development for partner employees, including a PhD by work-based, part-time study; (3) Deliver research for end-users through partner-funded PhDs with collaborating academics, accelerating knowledge exchange through PGR placements in partner workplaces; (4) Support the growth of an international network of partners working in aerosol science through focus meetings, conferences and training. Partners and academics will work together to deliver training to our cohorts, including in the areas of responsible innovation, entrepreneurship, policy, regulation, environmental sustainability and equality, diversity and inclusion.

The broad theme of the research training addresses the most rapidly developing parts of the bio-centred pharmaceutical and healthcare biotech industry. It meets specific training needs defined by the industry-led bioProcessUK and the Association of British Pharmaceutical Industry. The Centre proposal aligns with the EPSRC Delivery Plan 2008/9 to 2010/11, which notes pharmaceuticals as one of the UK's most dynamic industries. The EPSRC Next-Generation Healthcare theme is to link appropriate engineering and physical science research to the work of healthcare partners for improved translation of research output into clinical products and services. We address this directly. The bio-centred pharmaceutical sector is composed of three parts which the Centre will address:- More selective small molecule drugs produced using biocatalysis integrated with chemistry;- Biopharmaceutical therapeutic proteins and vaccines;- Human cell-based therapies.In each case new bioprocessing challenges are now being posed by the use of extensive molecular engineering to enhance the clinical outcome and the training proposed addresses the new challenges. Though one of the UK's most research intensive industries, pharmaceuticals is under intense strain due to:- Increasing global competition from lower cost countries;- The greater difficulty of bringing through increasingly complex medicines, for many of which the process of production is more difficult; - Pressure by governments to reduce the price paid by easing entry of generic copies and reducing drug reimbursement levels. These developments demand constant innovation and the Industrial Doctorate Training Centre will address the intellectual development and rigorous training of those who will lead on bioprocessing aspects. The activity will be conducted alongside the EPSRC Innovative Manufacturing Research Centre for Bioprocessing which an international review concluded leads the world in its approach to an increasingly important area .