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Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Everyone who reads a newspaper or watches the news on television will know that we are facing an energy crisis. The world's fossil-fuel energy reserves are dwindling and yet our thirst for energy is accelerating at an ever increasing rate. Scientists and engineers dream of solving this problem by harvesting the vast power of our Sun, storing its energy by breaking apart water and forming hydrogen gas. If only we could find an efficient and economical way of performing this chemical conversion the dream could become a reality. Our greatest hope today lies in harnessing the power of nature's own biological catalysts, enzymes, to promote desired chemical reactions. Enzymes are extremely efficient catalysts that allow chemical reactions to take place billions of times faster than normal. Unfortunately, enzymes are limited to the specific set of chemical reactions that they evolved to catalyse. Attempts to tailor enzymes to our needs have so far been disappointing. This is not surprising given our poor understanding of how they work. Conventional theory is unable to account for the incredible increases by which a reaction is speeded up by enzymes. A new emerging theory of enzyme catalysis suggests that if we had a window on this world we would see enzymes manipulating a phenomenon called quantum mechanical tunnelling to their advantage. We envisage chemical reactions overcoming the energy barrier that slows their progress, not by climbing over it, but by tunnelling directly through it. Even more strange, we think that enzymes might use their subtle vibrations to squeeze the energy barrier, reducing its thickness, to promote tunnelling and speed up the reaction. This project seeks to determine whether enzymes have indeed evolved to manipulate quantum mechanics, by using their movements to accelerate chemical reactions. In order to do this a novel instrument will be constructed to provide a unique window on this world. This instrument is based on a technique called Electron Paramagnetic Resonance (EPR), a cousin of the more familiar Magnetic Resonance Imaging (MRI) technology seen in hospitals. While existing instruments use microwave radiation, which limits their ability to distinguish features, this new instrument will use radiation that lies between the microwave and infra-red parts of the spectrum, so-called terahertz radiation. This will result in structural information being revealed in exquisite detail. In addition, flashes of terahertz radiation will be generated using pulses of laser light lasting less than one millionth of a millionth of a second enabling snap-shots to be taken of enzymes in action. The ability to watch these fast tunnelling processes is essential to our understanding of enzyme function and is far beyond the reach of existing instruments. Producing these action-packed enzyme movies with such high-definition structural information will rely on the precise timing between multiple bursts of terahertz radiation. To achieve these ambitious goals this project brings together a combination of industrial and academic collaborators with expertise in laser development, advanced EPR measurements and apparatus, and enzyme catalysis. Under my leadership, this project will provide knowledge crucially important to the successful exploitation of these remarkable biological catalysts.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Oxford's proposals for the use of the funds from this Platform Grant align closely with the objectives of the EPSRC's call for applications. We want to deploy this stable and flexible source of baseline funds to further the strategic development of our research agenda by means of initiatives that are not covered by more conventional project-oriented funding mechanisms. We plan to use part of the funding to accelerate our expansion in number theory, to coincide with the arrival of Andrew Wiles, enhancing the international and public profile of our initiative in this area. Secondly, we will set up a pump-priming fund specifically aimed at projects which, due to their speculative nature, are not yet ready for external funding applications (perhaps due to their novel interdisciplinary nature), but which have every possibility of being high-impact projects in the medium term. We have several such feasibility studies in incubation already but no means of funding them; a specific example highlighted in the proposal is an adventurous proposal in the field of mathematical neuroscience. The mechanism for this pump-priming activity is designed to enhance the experience of our large pool of highly-talented postdoctoral researchers, smoothing out transition periods between major grants and providing postdoctoral researchers with a valuable diversity of experience. Thirdly, we want to pump-prime in a different manner: in this alternative model, we will fund nascent projects that we expect to lead to new or enhanced international collaborations that will leverage large grants from overseas funders. A specific example that we give for this type of activity involves a project that we expect, when properly nurtured, to attract large-scale funding from the National Institutes of Health in the USA; it involves the mathematical modelling of tumour growth. Team Development and the nurturing of human capital for the wider benefit of society (with particular emphasis on early career researchers) are important aspects of our research strategy. We see the development of a strong Visitor Programme as an enormously important step in this direction and will deploy a significant part of the funds from this grant in funding such a programme, with a rigorous internal competition to identify the visitors to be funded. We wish to implement to ensure a coherent flow of visitors of the highest possible calibre to Oxford for periods ranging from a few weeks to a term. Many of our international competitors have guaranteed funding for Visiting Professors, but presently we do not. We want the very best and most exciting mathematicians to visit Oxford on a regular basis, above all so that the younger members of our research teams have direct access to these scientists and interact with them, thereby gaining a clear view of the level that they must aspire to, and becoming engaged with the global structure driving their field.A similar mechanism will be used to implement a travel programme for mathematicians wishing to foster links with international collaborators: proposals will be judged on mathematical merit and should include plans to perpetuate the collaboration from other funding sources. In addition, a programme of workshops will be funded through a structure that gives us the ability to organise workshops in a rapid and coherent manner, responding to exciting emerging trends, or to pressing challenges from outside mathematics. All workshops will be required to assess the possibility of a public outreach event, and to organise such an event where relevant. As part of our drive in number theory we expect to hold at least two workshops, one in analytic aspects of the subject and one around Galois representations; each would be accompanied by a public event.

There is general agreement that medical science is facing a problem of grave importance with implications for the future of human health.Due to the evolution and spread of antibiotic resistant bacteria and the increasing difficulty of synthesising new antibiotic products,we need to find new ways of treating bacterial infections. As we embark upon the design of synthetictherapies that exploit engineered bacteria and their viral bacteriophages, we need to better understand how to use the antimicrobial agents in our possession.Locating 'the optimal antibiotic treatment' may be a distant goal, but researchers have recently begun to consider new ways in whichantibiotics should be combined to minimise the evolution of resistance to antibiotics. This is the focus of the proposal: how do wego beyond pharmacokinetic measures of efficacy to find new rationales for the optimal treatment?An approach to this question must encompass different fields. We need tools from systems biology thattell us how to model the behaviour of the complex processes within a single cell, but we also need modelsdescribing how antibiotics inhibit those cellular processes and lead to death in bacteria: the systems biology of antibiotics. To test theory we need empirical work, for if we claim that a combination of different antibiotics makes a potent cocktail, we should then test the veracity of this claim in the lab.The experimental paradigm for the type of research questions tackled in the proposal are 'experimental microbial systems', evolving microcosms that can be created in vitro and their evolution observed and repeated. Indeed, the evolution of antibiotic resistance can be so rapid that it may be observed in experiments lasting a handful of days. The utility of this empirical device is the rapidity with which hypotheses can be tested, we will soon see whether ideas created in theory have any validity in practise.But how do we derive such theoretical predictions? By taking mathematical models of experimental systems and asking fora form of 'controllability'. That is, we first ask whether a particular outcome can be achieved within the mathematical model. This outcome might mean, for example, using antibiotics to removal a bacterium from its host by minimising its density while, at the same time, preventing that bacterium from evolving antibiotic resistance; we claim that this kind of problem fits nicely into a systems and control approach.Despite very rapid advances in genomic technologies, biological systems are notoriously hard to model and data can be sparse so we will need to work hard to control them. However, a fundemental feature of the work we propose is the principle of generality that may help see beyond data. The idea, a common mathematical technique, is to look for principles that identify different systems as having identical structures that can be dealt with abstractly using mathematical tools. For example, are there any principles common to the best antibiotic cocktails when treating both E.coli or Pseudomonas infections? Are treatments that cycle different antibiotics in time always better than ones that mix antibiotics into a single cocktail? Is the particular antibiotic protein target within the cell important? Mathematics can help elucidate general problems like these.As some of these problems are difficult and ambitious, more feasible goals are presented. For example, can we use imaging to watch bacterial colonies grow in different antibiotic media and predict and measure the potency of different cocktails? This kind of experiment is novel in itself and will provide a foundation for more theoretical parts of the work.In short, with a combination of tools from mathematics, biology and physics our aim is to understand what the optimalantibiotic treatments are in simple systems and to understand whether those treatments remain optimal for more complex biological systems.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Nanotechnology is a significant enabling research activity at both a national and international level. Concerned with the manipulation and arrangement of material on the nanometre-scale, the transformative possibilities of this field are immense for the physical, biological and medical sciences and their allied industrial and clinical applications. The universities of Leeds, York and Sheffield have an exceptionally strong international record of research and research-led teaching in nanotechnology and represent a strong regional focus in the UK in this field. Much research is carried out collaboratively and inter-disciplinarily in well-resourced and sustainably managed facilities.However, despite the strength of such existing activities, it is clear that certain capabilities require an urgent and substantial transformation if we are to continue to offer internationally competitive research in this field over the next decade. Specifically - and the objective of this proposal - there is a pressing need to establish a state-of-the-art electron-beam lithography machine for fabrication of structures with a <10 nm resolution, with highly reproducible stitching and overlay accuracy <20 nm. The proposed facility would not only be unique in the region, but will also be leading both in the UK and internationally. It will meet the future needs of researchers over the next decade and beyond, allow us to capitalise on previous investments, grow research income from a wide variety of sources, attract and retain the highest calibre staff in the UK, and build a capability to develop a skill-set for ambitious, adventurous and transformative research, and exploitation. Furthermore, it will act as a focus in the region, drawing in researchers from industry and other universities for collaborative programmes. Such direct engagement with industry will open up routes for further investment as well as exploitation of new science and technology. A wide range of research will benefit, much cross-disciplinary; immediate exemplars, drawing upon proven track records of the investigators, include research into nanomagnetism, spintronics, bio-nanotechnology, nanoelectronics, single-molecule devices, and high-frequency electronics, inter alia. During this programme, the facility will be used to support both a range of existing grants, and to underpin future grants, many of which cannot be contemplated without the planned enhancement in capability.Significant contributions to this project (41% of the overall project value) have been secured from the University of Leeds, where the new facility will be based, Yorkshire Forward (the regional development agency), and the electron beam lithography instrument manufacturer. The latter two contributions will be combined to provide funding for 10 PhD studentships to aid uptake of the instrument from researchers across the region, enable pump-priming proving research to be carried out, draw industrial involvement into the project, and increase the availability of skilled personnel at a world leading level to facilitate high technology development. The strong industrial support for this programme is evidenced by letters of intent provided both by international companies (eg Hitachi, Intel, Seagate, Toshiba), and local SMEs (eg Aptuscan).

Nuclear fission is currently internationally recognised as a key low carbon energy source, vital in the fight against global warming, which has stimulated much interest and recent investment. For example, RCUK's energy programme has identified nuclear fission as an essential part of the "trinity" of future fuel options for the UK, alongside renewables and clean coal. However, nuclear energy is controversial, with heartfelt opinion both for and against, and there is a real requirement to make it cleaner and greener. Large international programmes of work are needed to deliver safe, reliable, economic and sustainable nuclear energy on the scale required in both the short and long term, through Gen III+ & Gen IV reactor systems. A pressing worldwide need is the development of specific spent fuel reprocessing technology suitable for these new reactors (as well as for dealing with legacy waste fuel from old reactors). The REFINE programme will assemble a multidisciplinary team across five partner universities and NNL, the UK's national nuclear laboratory to address this fuel reprocessing issue. The consortium will carry out a materials research programme to deliver fuel reprocessing by developing materials electrosynthesis through direct oxide reduction and selective electrodissolution and electroplating from molten salt systems. Developing, optimising and controlling these processes will provide methods for, and a fundamental understanding of, how best to reprocess nuclear fuel. This is in addition to the development of techniques for new molten salt systems, new sensing and analysis technologies and the establishment of the kinetics and mechanisms by which molten salt processes occur. This will facilitate rapid process development and optimization, as well as the generation of applications in related areas. A key output of the programme will be the training and development of the multidisciplinary UK researchers required to make possible clean nuclear energy and generate complementary scientific and technological breakthroughs.