Chemical technologies underpin almost every aspect of our lives, from the energy we use to the materials we rely on and the medications we take. The UK chemical industry generates £73.3 billion revenue and employs 161,000 highly skilled workers. It is highly diverse (therefore resilient) with SMEs and microbusinesses making up a remarkable 96% of the sector. Today's global chemicals industry is responsible for 10% of greenhouse gas (GHG) emissions and consumes 20% of oil and gas as carbon feedstock to make products. Decarbonisation (defossilisation) of the chemicals sector is, therefore, urgently required, but to do so presents major technical and societal challenges. New sustainable chemical technologies, enabled by new synthesis, catalysis, reaction engineering, digitalisation and sustainability assessment, are needed. In order to ensure that the UK develops a resource efficient, resilient and sustainable economy underpinned by chemical manufacturing, developments in chemical technologies must be closely informed by whole systems approaches to measure and minimise environmental footprints, understand supply chains and assess economic and technological viability, using techniques such as life cycle assessment and material flow analysis. Lack of access to experts in science and engineering with a holistic understanding of sustainable systems is widely and publicly recognised as a significant risk. It is therefore extremely timely to establish a new EPSRC CDT in Sustainable Chemical Technologies that fully integrates a whole systems approach to training and world leading research in an innovation-driven context. This CDT will train the next generation of leaders in sustainable chemical technologies with new skills to address the growing demand for highly skilled PhD graduates with the ability to develop and transfer sustainable practices into industry and society. The new CDT will be a unique and vibrant focus of innovative doctoral training in the UK by taking full advantage of two exciting new developments at Bath. First, the CDT will be embedded in our new Institute for Sustainability (IfS) which has evolved from the internationally leading Centre for Sustainable and Circular Technologies (CSCT) and which fully integrates whole systems research and sustainable chemical technologies - two world-leading research groupings at Bath - under one banner. Second, the CDT will operate in close partnership with our recently established Swindon-based Innovation Centre for Applied Sustainable Technologies (iCAST, www.iCAST.org.uk) a £17M partnership for the rapid translation of university research to provide a dynamic innovation-focused context for PhD training in the region. Our fresh and dynamic approach has been co-created with key industrial, research, training and civic partners who have indicated co-investment of over £17M of support. This unique partnership will ensure that a new generation of highly skilled, entrepreneurial, innovative PhD graduates is nurtured to be the leaders of tomorrow's green industrial revolution in the UK.

Lipid nanoparticles (LNPs) are small self-assembled particles of approximately 100 nanometres in diameter, which are able to encapsulate and protect biologically active molecules such as nucleic acids (RNA or DNA) so to deliver the payload intact to the inside of cells. LNPs are used to deliver COVID-19 mRNA vaccines, with spectacular success. However, how it works is still something of a 'black-art', due to a lack of detailed understanding at a molecular level of the factors which control each stage of this very complex process. The protein output of messenger RNA (mRNA) has long been understood to be dependent on the rate of translation initiation and secondary structures formed by mRNA were thought to hinder elongation. Unexpectedly, recent studies found that greater mRNA translation is correlated to highly structured coding sequences, resulting in increased functional mRNA half-life as well as protein output. Currently, we have not only screened hundreds of internal AstraZeneca ionisable lipids that form part of the LNPs using in vitro cellular assays, but also optimised RNA primary sequence to improve its translatability, stability and immunogenicity in order to increase the biological performance. To our knowledge, the mRNA higher order structure inside LNPs and its effect on the rate of mRNA endosomal escape inside cells have not been studied. This information is beneficial in the rational design of the optimal mRNA sequence to enable more efficient and safer intracellular delivery of mRNAs and other nucleic acids for vaccines and other advanced treatments such as gene editing. In this project, we will initiate the first attempt to understand the effects of mRNA primary sequence and its resultant secondary/ tertiary structure on endosomal escape, which impacts mRNA expression. We aim to take advantage of the state-of-the-art facilities at the Rutherford Appleton Laboratory to generate high quality structural data from LNPs formulated with a set of mRNA sequences developed by AstraZeneca. The techniques we will use are Small Angle X-ray Scattering (SAXS) , Small Angle Neutron Scattering (SANS), and cryogenic Transmission Electron Microscopy (cryo-TEM). Synchrotron SAXS at Diamond Light Source is a very powerful way of probing the mRNA structure in solution as well as identifying and characterising liquid-crystalline or other types of ordering of the LNPs. SANS at the ISIS Neutron and Muon Source has the unique ability to determine the distribution of the different lipids and mRNA within the LNPs. This approach takes advantage of a unique feature of neutron scattering, whereby molecules can be 'highlighted' by substituting deuterium for hydrogen in the chemical structure of the synthesized molecule and/or that of the buffer. Cryo-TEM is able to give structural details of mRNA in solution and in an LNP. The experimental work will be complemented by computer simulations of the interaction of mRNA with the lipids.

Single crystals are materials in pristine, perfect form. Most people interact with them daily, from gemstones (emeralds, rubies) to silicon-based transistors (computer chips). Their ubiquity and importance to modern life are due to their quality and reproducibility; they are perfectly engineered materials with precise dopants that produce reliable and powerful technologies. That said, we have relied on remarkably few materials in single crystalline form for our technological development. Examples are silicon, Gallium arsenide and cadmium telluride. For emerging technologies in optoelectronics and quantum computing, we will require single crystals of new materials that underpin these new sectors of science and engineering. We aim to create a unique UK crystal growth facility whose centrepiece will be a laser-heated, ultra-high-pressure floating zone furnace (HP-LFZ). This facility will produce large, cubic-centimetre scale single crystal ingots of new material systems previously unavailable to UK scientists and industry. It will benefit a broad range of scientists and engineers, notably condensed matter physicists, electronic and chemical engineers, and laser physicists. The facility will be open to all UK scientists and engineers; we will provide training and free equipment access to enable users to synthesise their desired materials. The HP-LFZ is a recent leap forward in crystal growth methods. It opens a new regime of temperature and pressure (2500 Celcius / 300 bar gas pressure) for the growth of materials from the melt in the form of large (> 1 cubic centimetre), high-quality single crystals and is particularly suited to realising crystals of volatile or incongruently melting materials that are unavailable to standard melt-growth techniques.

Cationic biocides are a group of disinfectants widely used to disinfect hard surfaces including hospital facilities (floors, beds and instruments), public infrastructures (stations, trains, theatres), schools and food processing hardware. In the post Covid era, effective disinfection of public facilities reduces the cross-contamination of transferable diseases, thereby cutting down the needs for hospitalisation and antibiotic treatment. Despite the widespread use of cationic biocides and the urgent need to mitigate the antimicrobial resistance, our current understanding of how cationic biocides work is very limited. This lack of understanding severely limits our ability in both the improvement of our current products and innovation of new products. Current approaches applied in biocide formulations do not have direct access to interfacial structures, i.e., how a biocide binds to a given membrane and how the interactive process affects the interfacial structure and composition. There is thus an urgent need to get such insight and improve our current formulation capability and approach. The novelty of this project lies in the partnership of our industrial partner Arxada with STFC's ISIS Neutron and Muon Source, and the University of Manchester (UoM) to engage in the challenges that hinder the biocide formulation. Our previous funded work has focused on unravelling how DDAC, a representative biocide of quats (quaternary ammonium compounds) bound to membrane models mimicking the inner and outer membranes of Gram-negative bacteria, with and without nonionic surfactant C12E6 as an auxiliary molecule. The results revealed that the combined use of H/D substitutions to lipids, DDAC and water enabled parallel neutron runs, which hugely improved the structural resolutions of neutron reflectometry (NR) and small angle neutron scattering (SANS) through joint data analysis. The neutron data have enabled us to observe how DDAC disrupted the outer and inner membranes, showing distinct structural characteristics that could not be accessed by any other means. This proposal requests further support from this call to extend this combined approach to membrane models mimicking Gram-positive bacterial outer cell surface and membrane to demonstrate the consolidation of the technical capability by revealing bacteria-type specific structural features that could be linked to the consequent impact on bactericidal efficacy and dynamic kills. High efficacy and fast action of biocides are essential to ensure high public hygiene standard, as weak or ineffective deactivation of microbes could lead to outbreaks with dire consequences. Understanding the roles of the ingredients in formulated biocides is the basis of adjusting existing formulations and developing more effective ones, with direct benefits to the public. Better prevention would potentially lead to fewer acquired infections that would need antibiotics intervention whence indirectly this would also help mitigate the increased antimicrobial resistance issue in healthcare. Prof Lu has collaborated extensively with Dr Webster and Dr Li in the application of neutron research through the joint development of new neutron sample environment and deuteration of surfactants and lipids. Prof Petkov is our industrial partner and a long-term collaborator, starting from his previous employment with Unilever. The BBSRC-STFC Facility Access Funding call offer a unique opportunity for Arxada to benefit from the world leading neutron facility and skills at ISIS and the membrane models at UoM to develop a neutron-based approach that could enhance their formulation capability by linking interfacial binding of biocides to antimicrobial efficacy and dynamic kill.

Our CDT in Inorganic Materials for Advanced Manufacturing (IMAT) will provide the knowledge, training and innovation in Inorganic Chemistry and Materials Science needed to power large-scale, high-growth, current and future manufacturing industries. Our cohort-centred programme will build the skills needed to understand, transform and discover better products and materials, and to tackle the practical challenges of manufacturing, application and recycling. IMAT CDT addresses the 'Meeting a user need' CDT focus area, while also addressing 3 EPSRC strategic priorities: 'Physical Sciences Powerhouse', 'Engineering Net Zero' and 'Quantum Technologies'. 'Inorganics' are essential to many industries, from fuel cells to electronics, from batteries to catalysts, from solar cells to medical imaging. These materials are made by technically skilful chemical transformations of elements from across the breadth of the Periodic Table: success is only achievable via in-depth understanding of their properties and dynamic behaviour, requiring systems-thinking across the boundaries of Chemistry and Materials Science. The sector is characterized by an unusually high demand for high-level (MSc/PhD) qualified employees. Moreover, wide-ranging synergies in manufacturing challenges for 'inorganics' mean significant added value is attached to interdisciplinary training in this area. For example, understanding ionic/electronic conductivity is relevant to thermo-electric materials, photo-voltaics, batteries and quantum technologies; replacing heavy metals with earth-abundant alternatives is relevant to chemical manufacturing from plastics to fragrances to speciality chemicals; and methods to manufacture starting from 'natural molecules' like water, oxygen, nitrogen and CO2 will impact nearly every sector of the chemical industry. IMAT will train graduates to navigate interconnected supply chains and meet industry technology/sustainability demands. To invent and propel future industries, graduates must have a clear understanding of scientific fundamentals and be able to quickly apply them to difficult, fast-changing challenges to ensure the UK's leadership in high-tech, high-growth industries. A wide breadth of technical competence is essential, given the sector dominance of small enterprises employing <50 people. The 'inorganic' sector must also meet challenges associated with resource sustainability, manufacturing net zero, pollution minimisation and recycling; our cohorts will be trained to think broadly, with awareness of environmental, societal, legal and economic factors. Our creative and highly skilled graduates will transform sectors as diverse as energy generation, storage, electronics, construction materials, consumer goods, sensing/detection and healthcare. IMAT builds upon the successful EPSRC 'inorganic synthesis' CDT (OxICFM) and (based on extensive end-user/partner feedback) expands its training portfolio to include materials science, physics, engineering and other areas needed to equip graduates to tackle advanced materials challenges. It addresses local, national and international skills gaps identified by our partners, who include companies spanning a wide range of business sizes/sectors, together with local enterprise partnerships and manufacturing catapults. IMAT offers a unique set of training goals in 'inorganic' chemistry and materials - a key discipline encompassing everything made which is not an organic molecule: from salts to composites, from acids/bases to ceramics, from organometallics to (bio)catalysts, from soft-matter to the toughest materials known, and from semi-conductors to super-conductors. A unifying training spanning this breadth is made possible through the strength of expertise across Oxford Chemistry and Materials, and our national partner network. Our goal is to empower future graduates by equipping them with this critical knowledge ready to apply it to new manufacturing sectors.