The chemical and pharmaceutical industries are currently reliant on petrochemical derived intermediates for the synthesis of a wide range of valuable chemicals, materials and medicines. Decreasing petrochemical reserves, and concerns over increasing cost and greenhouse gas emissions, are now driving the search for renewable and environmentally friendly sources of these critically needed compounds. This project aims to establish a range of new manufacturing technologies for efficient conversion of biomass in agricultural waste streams into sustainable sources of these valuable chemical intermediates. The UK Committee on Climate Change (2018) has highlighted the importance of the efficient use of agricultural biomass in tackling climate change. The work undertaken in this project will contribute to this effort and help the UK government achieve its stated target of 'net-zero emissions' by 2050. The new approaches will be exemplified using UK-sourced Sugar Beet Pulp (SBP) a renewable resource in which the UK is self-sufficient. Over 8 million tonnes of sugar beet is grown annually in the UK on over 3500 farms concentrated in East Anglia and the East Midlands. After harvest, the beet is transported to a small number of advanced biorefineries to extract the main product; the sucrose we find in table sugar. SBP is the lignocellulosic material left after sucrose extraction. Currently it is dried (requiring energy input) and then sold as a low-value animal feed. SBP is primarily composed of two, naturally occurring, biological polymers; cellulose and pectin. Efficient utilisation of this biomass waste stream demands that applications are found for both of these. This work will establish the use of the cellulose nanofibres for making antimicrobial coatings and 3D-printed scaffolds (in which cells can be cultured for tissue engineering and regenerative medicine applications). The pectin will be broken down into its two main components: L-arabinose and D-galacturonic acid. The L-arabinose can be used directly as a low-calorie sweetener to combat the growing problem of obesity. The D-galacturonic acid will be modified in order to allow formation of biodegradable polymers which have a wide range of applications. This new ability to convert SBP into a range of useful food, chemical and healthcare products is expected to bring significant social, economic and environmental benefits. In conducting this research we will adopt a holistic approach to the design of integrated biorefineries in which these new technologies will be implemented. Computer-based modelling tools will be used to assess the efficiency of raw material, water and energy utilisation. Techno-Economic Analysis (TEA) and Life Cycle Analysis (LCA) approaches will be employed to identify the most cost-effective and environmentally benign product and process combinations for potential commercialisation. The results will be widely disseminated to facilitate public engagement with the research and ethical evaluation. In this way the work will support the UK in its transition to a low-carbon, bio-based circular economy.

Industrial Biotechnology (IB) is entering a golden age of opportunity. Technological and scientific advances in biotechnology have revolutionised our ability to synthesise molecules of choice, giving access to novel chemistries that enable tuneable selectivity and the use of benign reaction conditions. These developments can now be coupled to advances in the industrialisation of biology to generate innovative manufacturing routes, supported by high throughput and real-time analytics, process automation, artificial intelligence and data-driven science. The current excess energy demands of manufacturing and its use of expensive and resource intensive materials can no longer be tolerated. Impacts on climate change (carbon emissions), societal health (toxic waste streams, pollution) and the environment (depletion of precious resources, waste accumulation) are well documented and unsustainable. What is clear is that a petrochemical-dependent economy cannot support the rate at which we consume goods and the demand we place on cheap and easily accessible materials. The emergent bioeconomy, which fosters resource efficiency and reduced reliance on fossil resources, promises to free society from many of the shortcomings of current manufacturing practices. By harnessing the power of biology through innovative IB, the FBRH will support the development of safer, cleaner and greener manufacturing supply chains. This is at the core of the UKs Clean Growth strategy. The EPSRC Future Biomanufacturing Research Hub (FBRH) will deliver biomanufacturing processes to support the rapid emergence of the bioeconomy and to place the UK at the forefront of global economic Clean Growth in key manufacturing sectors - pharmaceuticals; value-added chemicals; engineering materials. The FBRH will be a biomanufacturing accelerator, coordinating UK academic, HVM catapult, and industrial capabilities to enable the complete biomanufacturing innovation pipeline to deliver economic, robust and scalable bioprocesses to meet societal and commercial demand. The FBRH has developed a clear strategy to achieve this vision. This strategy addresses the need to change the economic reality of biomanufacturing by addressing the entire manufacturing lifecycle, by considering aspects such as scale-up, process intensification, continuous manufacturing, integrated and whole-process modelling. The FBRH will address the urgent need to quickly deliver new biocatalysts, robust industrial hosts and novel production technologies that will enable rapid transition from proof-of-concept to manufacturing at scale. The emphasis is on predictable deployment of sustainable and innovative biomanufacturing technologies through integrated technology development at all scales of production, harnessing UK-wide world-leading research expertise and frontier science and technology, including data-driven AI approaches, automation and new technologies emerging from the 'engineering of biology'. The FBRH will have its Hub at the Manchester Institute of Biotechnology at The University of Manchester, with Spokes at the Innovation and Knowledge Centre for Synthetic Biology (Imperial College London), Advanced Centre for Biochemical Engineering (University College London), the Bioprocess, Environmental and Chemical Technologies Group (Nottingham University), the UK Catalysis Hub (Harwell), the Industrial Biotechnology Innovation Centre (Glasgow) and the Centre for Process Innovation (Wilton). This collaborative approach of linking the UK's leading IB centres that hold complementary expertise together with industry will establish an internationally unique asset for UK manufacturing.

This UKRI Fellowship will support my development of a new scientific expertise at Keele University which interfaces chemistry and biology. The overarching goal of the research is to develop an efficient technology to provide biologically important carbohydrates. Specifically, a class of oligosaccharides (where multiple carbohydrate monomers are linked together to form a chain) called heparan sulfates. Heparan sulfates are very important regulators within biology, mediating pathological conditions including cancer, Alzheimer's disease, viral infections such as HIV and HSV and numerous bacterial infections. Therefore, there is a real need to interrogate and fundamentally understand the biological role that heparan sulfate plays in these processes. This will allow scientists to formulate a precise picture of heparan sulfate-mediated structure-activity relationships and initiate the development of new treatments for the pathophysiologies that they control. Chemical synthesis of heparan sulfates is particularly challenging and has traditionally always been completed using solution-phase reactions. Whilst there have been significant achievements in this field, the time and resource required to enable such 'total' syntheses is vast and more efficient methods must be found. This challenge will be addressed by automating heparan sulfate production using a machine-based synthesis and then modifying the materials obtained with enzymes to install specific features that enable their biological function. Such a methodology would revolutionise how quickly we can access these materials, which is absolutely necessary to study and understand their ubiquitous regulatory biology. In undertaking this research, I will adopt a multidisciplinary approach consisting of a fusion between traditional organic chemistry, the evolving field of synthesis automation, and the innovative field of chemoenzymatic modification. This combination will facilitate the development of a faster and greener approach to biologically relevant heparan sulfates and overcome the current challenges presented in the building of biologically important carbohydrates. This is a rapidly evolving worldwide field which is currently underrepresented in UK science. The important materials provided by the technology and knowledge developed during this Fellowship will be used to probe these mechanisms of disease and aid the design and development of new therapeutics against them.

In project BIOBEADS we propose to develop, in combination, new manufacturing routes to new products. Manufacturing will be based on a low-energy process that can be readily scaled up, or down, and the products will be biodegradable microbeads, microscapsules and microsponges, which share the performance characteristics of existing plastic microsphere products, but which will leave no lasting environmental trace. Using bio-based materials such as cellulose (from plants) and chitin (from crab or prawn shells), we will use continuous manufacturing methods to generate microspheres, hollow capsules and porous particles to replace the plastic microbeads currently in use in many applications. Cellulose and chitin are biodegradable and also part of the diet of many marine organisms, meaning they have straightforward natural breakdown routes and will not accumulate in the environment. BIOBEADS will be produced using membrane emulsification techniques. The project builds on our joint expertise in membrane emulsification for continuous production of tunable droplet sizes, dissolution of cellulose and chitin in green solvents and in characterization of nanoscale and microscale structures to study all aspects of particle formation from precursors, through formation processes, to degradation routes. Yhe primary focus will be spheres and capsules, for use in cosmetics and personal care formulations, but, by understanding the processes and mechanisms of formation of these spheres, we aim to be able to tailor particle properties to suit larger scale applications from paint stripping, to fillers in biodegradable plastics. The BIOBEADS research team will work with industrial partners, including very large manufacturers of personal care products, to ensure that the research conducted can be taken up and used, so having a real, positive impact on the manufacturing of new, more sustainble products.

The CDT in Molecules to Product addresses an overarching concern articulated by industry operating in the area of complex chemical products. It centres on the lack of a pipeline of doctoral graduates who understand the cross-scale issues that need to be addressed within the chemicals continuum. Translating their concern into a vision, the focus of the CDT is to train a new generation of research leaders with the skills and expertise to navigate the journey from a selected molecule or molecular system through to the final product that delivers the desired structure and required performance. To address this vision, three inter-related Themes form the foundation of the CDT - Product Functionalisation and Performance, Product Characterisation, and Process Modelling between Scales. More specifically, industry has identified a real need to recruit PGR graduates with the interdisciplinary skills covered by the CDT research and training programme. As future leaders they will be instrumental in delivering enhanced process and product understanding, and hence the manufacture of a desired end effect such as taste, dissolution or stability. For example, if industry is better informed regarding the effect of the manufacturing process on existing products, can the process be made more efficient and cost effective through identifying what changes can be made to the current process? Alternatively, if there is an enhanced understanding of the effect of raw materials, could stages in the process be removed, i.e. are some stages simply historical and not needed. For radically new products that have been developed, is it possible through characterisation techniques to understand (i) the role/effect of each component/raw material on the final product; and (ii) how the product structure is impacted by the process conditions both chemical and mechanical? Finally, can predictive models be developed to realise effective scale up? Such a focus will assist industry to mitigate against wasted development time and costs allowing them to focus on products and processes where the risk of failure is reduced. Although the ethos of the CDT embraces a wide range of sectors, it will focus primarily on companies within speciality chemicals, home and personal care, fast moving consumer goods, food and beverage, and pharma/biopharma sectors. The focus of the CDT is not singular to technical challenges: a core element will be to incorporate the concept of 'Education for Innovation' as described in The Royal Academy of Engineering Report, 'Educating engineers to drive the innovation economy'. This will be facilitated through the inclusion of innovation and enterprise as key strands within the research training programme. Through the combination of technical, entrepreneurial and business skills, the PGR students will have a unique set of skills that will set them apart from their peers and ultimately become the next generation of leaders in industry/academia. The training and research agendas are dependent on strong engagement with multi-national companies, SMEs, start-ups and stakeholders. Core input includes the offering, and supervision of research projects; hosting of students on site for a minimum period of 3 months; the provision of mentoring to students; engagement with the training through the shaping and delivery of modules and the provision of in-house courses. Additional to this will be, where relevant, access to materials and products that form the basis of projects, the provision of software, access to on-site equipment and the loan of equipment. In summary, the vision underpinning the CDT is too big and complex to be tackled through individual PhD projects - it is only through bringing academia and industry together from across multiple disciplines that a solution will be achievable. The CDT structure is the only route to addressing the overarching vision in a structured manner to realise delivery of the new approach to product development.