University of Southampton

UKRI Gateway to Research · FY 2024 · 2024-07

Macromolecules such as proteins, DNA and RNA mediate the vast majority of processes that constitute and sustain life, including photosynthesis, metabolism, exchange of information between cells, and cellular replication. These processes depend crucially on the dynamic 3D structures that macromolecules adopt. Insights from studying the 3D structures of macromolecules have transformed both our understanding of living systems and our ability to use that understanding to promote health and use in biotechnology. Overwhelmingly, 3D structures were experimentally determined by macromolecular crystallography (MX, >85% of PDB entries), with additional contributions from nuclear magnetic resonance (NMR; dynamic, but typically limited to smaller structures) and rapidly growing input from electron microscopy (EM; typically membrane protein structures and macromolecular complexes, but studied under cryogenic conditions). The database of over 200,000 experimental structures is now informing deep learning approaches to predict macromolecular structure. In this exciting scientific landscape, MX plays a central discovery role, as well as validating and improving structure predictions, and complementing capabilities of other techniques. The present proposal deals with current challenges in the computational aspect of MX. In the process of MX, a crystal, formed from billions of copies of the macromolecule, is used to diffract X-rays or electrons; computational techniques then determine the underlying atomic structure. Knowledge of the molecule's 3D structure not only allows us to understand its function but also critically to design chemicals to interfere with it. Pharmaceutical research depends on the accuracy of experimental structures as the basis for designing drugs to turn the molecules on or off, or tune their function when required. Whilst the experimental pipeline today is partially automated and thus tremendously successful, key future challenges remain. Interactions of macromolecules with small and/or other macromolecules change their structure in ways that help to explain their function. There is now an opportunity to improve the strategies by which we capture and describe the family of structures that a macromolecule can adopt, especially with room-temperature methods. It is timely to develop tools that allow identification of different structural states present in a single experiment or in sets of related experiments. By recasting MX as a multi data-multi model process, this proposal will address a weakness that has previously limited the ability of MX to define the dynamics of macromolecules, and so to infer and predict functional properties. The work proposed here will improve structure analysis from both X-ray diffraction - the current predominant technique - and electron diffraction - a technique that can work with far smaller crystals, and so extend the utility of MX. Moreover, we propose to harness the power of deep learning approaches into the process of structure determination and validation for proteins, carbohydrates, DNA and RNA, as well as complexes containing one or more of these molecule-types. With a multi-technique, multi-data and multi model approach, we aim to deliver a dynamic description of the macromolecules that is closer to life, and therefore more descriptive of their function. The Collaborative Computing Project 4 was established in 1979 and continues to underpin world class macromolecular structural science in the UK. Effective use of data collected at synchrotron, XFEL and electron microscopy facilities is at the heart of the project's mission. User communities benefiting from such research include academics as well as industries. At the interface of the two, CCP4 enables discoveries that underlie vaccine and therapy discovery (including therapies and vaccines for SARS-CoV-2) and may equally be applied to tackle modern challenges in biotechnology and adaptation to climate change.

UKRI Gateway to Research · FY 2024 · 2024-07

There has been increased evidence in recent years about the health risks of air pollution, which contribute to millions of deaths globally and tens of thousands of UK deaths annually. This research is about improving our ability to model urban air pollution and wind patterns to inform policy affecting people's health and wellbeing. These scientific advances will be achieved by applying advanced aerospace approaches including scale-model aerodynamic testing, in-situ measurements in real-life buildings, and data-driven methods coupling measurements to computational fluid dynamics models. These novel approaches promise to reveal understanding of the dispersion and transport of pollutants from industrial and urban sources and advance our ability to monitor, model, and control airborne pollution at the local and city scales critical for urban flows. These techniques allow us to fill a gap in our knowledge about the influence of local flow patterns to pedestrian comfort, building optimisation, air quality, and macroscale weather prediction. The scale-model aerodynamics experiments will focus on using state-of-the-art optical diagnostic tools to reveal the wind patterns that are the mechanisms of pollution dispersion in and around building models. In the first part of this fellowship, novel experiments were developed using scale models in a recirculating water tunnel with dye as a proxy for air pollution. These experiments successfully replicated atmospheric boundary layer conditions and highlighted the importance of tall buildings in enhancing vertical transport of ground-level pollution out of the urban canopy. In this extension, particle tracking techniques and transparent city models will be employed to reveal the dynamics of the flow features at street level and within urban canyons. The lab measurements will be supplemented by in-situ measurements of real-life buildings. This is made possible by an interdisciplinary collaboration using University of Southampton campus buildings. These measurements will be an opportunity to validate models and will feed into the new data-driven approaches that will be used to analyse the results and translate them into industry impact. Data-driven methods aim to reduce the complexity of the turbulent flow models, fill in missing information, and reveal physics of the flow. Urban aerodynamics provides a novel application well-suited to this approach as key flow features are expected to be anchored by the terrain and novel as both velocity and concentration properties of the flow need to be captured in the physics. Impact to industry will continue to be fostered by working closely with the wind engineering community. Impact to policy will continue to be supported through case studies simulating air pollution in the city of Southampton and contributing to national strategy documents. The public outreach made possible through this fellowship also highlights that aerodynamics is not only relevant to aeroplanes and race cars and that a diversity of people can work in this field, showcasing "urban aerodynamics" as an emerging field of research. This fellowship extension is an opportunity to build on these foundations to broaden the inter-disciplinary applicability of the new science we uncover and translate the results into further policy-relevant and industry-relevant impact.

UKRI Gateway to Research · FY 2024 · 2024-07

Context We at the Centre for Music Education and Social Justice (CMESJ) at the University of Southampton (UoS) believe that music can be a transformative vehicle for change. As world-leading music scholars and social justice activists/practitioners, we advocate for creative approaches to ‘co-creating’ participatory projects between academics and diverse sectors of society (including, but not limited to, working-class and ethnic minority communities, disabled musicians, and those with mental health difficulties). As Hub for Public Engagement with Music Research, we will develop outcomes-focused, policy-driven project design models. Offering leadership in music, inclusion and disability (Lisa Tregale), music education, EDI and decolonisation (Erin Johnson-Williams), and practice-research in composition, technology and performance (Benjamin Oliver), our Hub will pioneer an accessible, participatory methodology that will be a model for funders, researchers, practitioners, organisations and public participants.   Challenge the project addresses Our outcomes-led approach will actively address historic gaps between music research and public engagement by empowering and upskilling academics and non-academics in connecting music research to real world settings, enabling outcomes to be captured, evaluated and shared effectively (e.g. policy briefs), for cross-sector impact.   Aims and objectives Our work packages will: 1) build, motivate and upskill a UK-wide network of researchers and music professionals invested in public engagement and social justice through training including from the UoS Public Engagement with Research Unit; 2) inspire and mentor spoke applications that use participatory music research and knowledge exchange as a means of social change; 3) support the successful delivery of 4 evidence-based spoke projects informed by ‘Theory of Change’ methodologies; and 4) provide world-class policy briefing support from Public Policy Southampton through allocating a Policy Associate researcher to each spoke project. These objectives will ensure that the Hub will support spoke projects that empower musicians who may have faced barriers to accessing traditional research funding to build quality and impact into the heart of their work, disseminating their findings in innovative and dynamic ways (i.e. through open-access training and policy documents). Holding regional networking events across the 4 countries of the UK will also increase the national reach of the Hub.   Potential applications and benefits Short-term outcomes include: developing relationships between researchers and music practitioners working in industry, community, education and/or health settings; increasing positive attitudes to participatory research and evidence-informed practice in real world settings; growing confidence in advocating for the impact of music through policy-led activist research; and building skills in designing research projects with effective public engagement goals that will be measured by policy briefing documents and an Executive Summary.   Medium/Long-term outcomes include: capacity building for community partners to engage with researchers; changes in public attitudes; and strengthened networks across UK music and non-music sectors, which can be nurtured by the infrastructure of Southampton’s CMESJ, with our links to organisations, communities, and global scholarly network invested in critical approaches to social justice. Our Hub will be a powerful catalyst for new ways of building and evaluating public engagement with music research, influencing creative and academic sectors as well as areas of governmental policy.

UKRI Gateway to Research · FY 2024 · 2024-06

The project aims to develop a Laboratory that will house Flow Facilities with Refractive-Index-Matched Solution (FoRMS lab). The lab comprises of two recirculating fluid flow loops designed to carry out experiments by matching the refractive index of the fluid with that of clear-solid models. Typically, laser diagnostics provides full-field information in areas of a flow where there is optical access. However, it is impossible to gain optical access in most complex flows where the important information is near the surface, within the substrate or is obscured by the model. This inaccessibility can be solved by matching the refractive index of the solid to the fluid, which allows access to laser-based flow diagnostics techniques like particle image velocimetry (PIV) and obtaining full-flow field data in previously inaccessible locations. We aim to use to Sodium Iodide salt solution that has the same refractive index as most PMMA. Therefore, models made from acrylic/perspex etc as well as silicone elastomers will have the same index of refraction as the fluid. These materials are ideal for rapid manufacture of model using a combination of 3D printing as well as casting and moulding techniques. We will be able to carry out high-fidelity experiments where new full-field velocity information can be obtained in complex flows that enables using transition to a data-driven modelling paradigm that has remained elusive for these complex flows.

UKRI Gateway to Research · FY 2024 · 2024-06

Fullerene molecules are hollow cages of carbon atoms, for the discovery of which the British scientist Harry Kroto won the Nobel prize in 1996. Inside the cage is an empty space. Chemists and physicists have found many ingenious ways of trapping atoms or molecules inside the tiny fullerene cages. These encapsulated compounds are called endofullerenes. "Molecular surgery" is a remarkable synthetic method. First, a series of chemical reactions is used to open a hole in the fullerene cages. A small molecule such as water (H2O) is inserted into each fullerene cage by using high temperature and pressure. Finally, a further series of chemical reactions is used to "sew" the holes back up again. The result is the remarkable chemical compound called water-endofullerene, denoted H2O@C60. Our team has succeeded in developing new synthetic routes which have allowed the synthesis of endofullerenes containing a broader range of molecules, such as HF@C60 and CH4@C60. Larger fullerenes than C60 exist. The fullerene C70 consists of ellipsoidal carbon cages, surrounding a cavity which is larger than that of C60. The cavity of C70 may accommodate two atoms or small molecules. We propose to create such systems, and study the properties of the encapsulated molecules and atoms. One example is C70 containing two 3He atoms. The two 3He atoms are squeezed together by confinement inside the same cavity, and comprise an "artificial molecule" which cannot exist without confinement. We will synthesise such C70 endofullerenes, and study their quantised rotational, vibrational, and translational motions, using a variety of electromagnetic spectroscopic techniques as well as inelastic neutron scattering. The study of such systems will provide a wealth of experimental data on non-covalent interactions. Such information is very valuable since (1) non-covalent interactions are critically important for a wide range of materials and biomolecular properties, and (2) non-covalent interactions are hard to estimate for systems of reasonable size by current computational chemistry techniques. Some C70 endofullerenes will display spin isomerism, meaning that there are different varieties of the same compound, differing only by the way the nuclear magnetic moments are aligned with respect to each other. Such compounds will be particularly interesting if they also contain unpaired electron spins. For such systems, the energy splitting associated with the spin isomerism may be brought into coincidence with the energy splitting between the electron spin states, induced by an applied magnetic field. We expect to observe unique spectroscopic phenomena in such systems including highly selective magnetic-field-induced spin-isomer conversion. This conversion may be accompanied by enhancement of nuclear magnetic resonance signals. This phenomenon can eventually lead to new ways to enhance magnetic resonance imaging signals, with applications to the imaging of materials and in the clinical sciences.

UKRI Gateway to Research · FY 2024 · 2024-06

The need for the UK to shift to NetZero was highlighted at COP26 in Glasgow, and there is a clear need for UK energy security. UK policy to achieving these is based on massive expansion of off-shore wind. In 2022 Crown Estate Scotland "ScotWind" auctioned 9,000 km2 of sea space in the northern North Sea, with potential to provide almost 25 GW of offshore wind. Further developments are planned elsewhere, for example, the 300 MW Gwynt Glas Offshore Wind Farm in the Celtic Sea. These developments mark a shift in off-shore wind generation, away from shallow, well mixed coastal waters to deeper, seasonally stratified shelf seas This shift offers both challenges and opportunities which this proposal will explore. Large areas of the NW European shelf undergo seasonal thermal stratification. This annual development of a thermocline, separating warm surface water from cold deep water, is fundamental to biological productivity. Spring stratification drives a bloom of growth of the microscopic phytoplankton that are the base of marine food chains. During summer the surface layer is denuded of nutrients and primary production continues in a layer inside the thermocline, where weak turbulent mixing supplies nutrients from the deeper water and mixes oxygen and organic material downward. Tidal flows generate turbulence; the strength of turbulence controls the timing of the spring bloom, mixing at the thermocline, and the timing of remixing of the water in autumn/winter. Determining the interplay between mixing and stratification is fundamental to understanding how shelf sea biological production is supported. Arrays of large, floating wind turbines are now being deployed over large areas of seasonally-stratifying seas. These structures will inject extra turbulence into the water, as tidal flows move through and past them. This extra turbulence will alter the balance between mixing and stratification: spring stratification and the bloom could occur later, biological growth inside the thermocline could be increased, and more oxygen could be supplied into the deep water. There could be significant benefits of this extra mixing, but we need to understand the whole suite of effects caused by this mixing to aid large-scale roll-out of deep-water renewable energy. eSWEETS3 will conduct observations at an existing floating wind farm in the NW North Sea to determine how the extra mixing generated by tides passing through the farm affect the physics, biology and chemistry of the water. We will measure the mixing of nutrients, organic material and oxygen within the farm, and track the down-stream impacts of the mixing as the water moves away from the wind farm and the phytoplankton respond to the new supply of nutrients. We will use autonomous gliders to observe the up-stream and down-stream contrasts in stratification and biology all the way through the stratified part of the year. We will use our observations to formulate the extra mixing in a computer model of the NW European shelf, so that we can then use the model to predict how planned renewable energy developments over the next decades might affect our shelf seas and how those effects might help counter some of the changes we expect in a warming climate. Stratification is so fundamental to how our seas support biological production that we will develop a new, cost-effective way of monitoring it. We will work with the renewables industry and modellers at the UK Met Office on a technique that allows temperature measurements to be made along the power cables that lie on the seabed between wind farms and the coast. Our vision is that large-scale roll-out of windfarms will lead to the ability to measure stratification across the entire shelf. This monitoring will help the industry (knowledge of operating conditions), government regulators (environment responses to climate change) and to operational scientists at the UK Met Office (constraining models for better predictions).

UKRI Gateway to Research · FY 2024 · 2024-06

This project will pioneer a new and highly efficient approach to the generation of hydrogen by combining heterojunction photocatalysts into Z-scheme arrangements. This will allow for the splitting of water into hydrogen and oxygen, using sunlight as the energy source, with an order of magnitude improvement over current state of the art photosystems. This "solar" hydrogen can be stored and subsequently used as a fuel or in fertiliser production, and is a sustainable and decarbonised source of hydrogen - in contrast to current production which requires natural gas. The impact of a source of sustainable hydrogen can be considered from several viewpoints. Energy storage is a key challenge as the UK switches to predominant use of renewable energy sources such as solar and wind, and away from natural gas and other fossil fuels. Conventional solar panels have a mismatch between winter electricity demand and generation biased towards the summer. In contrast, direct solar water splitting provides a complimentary class of solar energy, at lower cost, where the hydrogen can be stored during high production periods before conversion to electricity on demand when renewable energy supply is low. Hydrogen is also a valuable commodity chemical in its own right, for example in the production of ammonia for fertilisers. The ability to produce hydrogen using solar energy, and decrease dependence on natural gas, is a key component in tackling climate change while also enhancing energy security - which directly affects national security as recent events have shown. Large scale pilot studies have confirmed that photocatalytic systems can achieve complete water splitting into hydrogen and oxygen, but have not yet breached the 0.5% solar to hydrogen (StH) efficiency needed for the energy breakeven point, and are far from the ultimate target of 10% StH necessary for commercially viable 'green hydrogen' production. Our project will take the next steps needed to achieve this target. In photocatalysis, energy from sunlight is used to generate high energy electrons in the catalyst, leaving behind holes. These high energy electrons then drive the water splitting reactions at the surface of the catalyst. In order to achieve high efficiency, the photocatalyst must be able absorb a large fraction of the solar spectrum, prevent the electrons from recombining with their holes, and finally still maintain sufficient energy or overpotential to catalyse water splitting. We propose to combine two research strands to produce a new type of photosystem which can meet all three of these criteria. The first strand is the recent work on heterojunction photocatalysts. These are composed of particles of two different materials which allow for effective separation of the electron from the hole by trapping these in different parts of the catalyst, but which by themselves lack sufficient overpotential to carry out complete water splitting. The second strand is the work on 'Z-schemes' in which separate photocatalysts are used to maximise overpotential, by having an excited election transfer from one material to another to be 'boosted' by a second photon to a higher energy level to achieve water splitting. However, in Z-schemes the transfer process is slow, allowing time for recombination of the electrons and holes, reducing efficiency. We propose that by combining the heterojunction photocatalysts in a Z-scheme arrangement, it will be possible to create a photosystem that finally meet all three challenges. The heterojunctions will supress recombination, the Z-scheme will allow for large overpotential, and the system can make use of visible light absorbers to maximise solar energy uptake. We believe that because of the recent developments in visible light active heterojunctions, Z-scheme photosystems and demonstration of scale up, the time is now ripe to combine these research threads into a single photocatalytic system to achieve high efficiency water splitting.

UKRI Gateway to Research · FY 2024 · 2024-06

The National Biofilms Innovation Centre (NBIC) is seeking funding from the BBSRC to deliver and improve its annual FTMA calls for the next three years. Established in 2017, NBIC is an Innovation Knowledge Centre funded by BBSRC and Innovate UK, established in 2017 by four universities: Southampton, Liverpool, Nottingham, and Edinburgh. NBIC has a robust network, bringing together 63 academic and research partner institutions, and over 150 businesses focused on addressing biofilm challenges. The FTMA projects are popular and sought after within the NBIC biofilm community and valued for their impact. Over the past 5 years, NBIC has supported 43 projects through FTMA funding, fostering exchanges, placements, and training within its extensive biofilm network spanning and connecting academia and industry. The majority of these projects involved collaborations between academia and industry partners, including start-ups, SMEs, and large businesses, both within the UK and internationally. NBIC-FTMA will be open to a diverse range of participants, including investigators, postdoctoral research staff, research technical professionals, venture capitalists, and technology transfer offices. The annual open calls for FTMA projects will be managed by the NBIC Operational Team, with funds disbursed from the University of Southampton, which hosts the NBIC Office and Operational Team. The beneficiaries of the NBIC-FTMA awards will include early career researchers, research technical professionals from research organisations and industry R&D, industry partners, and the broader academic community. Successful awardees will be responsible for effectively managing the placements and reporting on the undertaken FTMA projects. The evaluation process will ensure that FTMA projects align with the NBIC strategic goals and the chosen UKRI priority area of 'Tackling infections', with a commitment to dedicating at least 25% of the projects to early career researchers and another 25% to research technical professionals. Success will be measured through metrics such as the transition of researchers into industry, securing follow-on funding, technology transfer, and the commercialisation of research outputs. Focusing on the priority area of "Tackling Infections," NBIC- FTMA projects will address the significant role that biofilms play in persistent infections and microbial contamination across various sectors, including healthcare settings, medical device-related infections, food safety, water systems, manufacturing, and other areas where control of pathogens is critical.

UKRI Gateway to Research · FY 2024 · 2024-06

Autonomous driving (AD) has a huge market and IS receiving enormous attention in both academia and industry. To deal with complex scenarios, autonomous vehicles (AVs) will use reinforcement learning (RL) to design high-level planners in the functional layer but always suffer from safety issues during sim-to-real transfer. One of the main challenges is that the current practice of functional-layer design does not sufficiently consider the uncertainty in the architecture layer, e.g., the software layer and hardware layer. This open challenge will be tackled in this project by a comprehensive study of the interaction between RL and architecture-layer uncertainty. Specifically, we will build virtual AD scenarios on the simulation platform with formal modeling of architecture-layer uncertainty based on real-world data (WP1). The impact of uncertainties on RL will be discussed via the design of cross-layer uncertainty-aware RL (WP2). Inversely, we will also study the robustness of an RL with respect to cross-layer uncertainty by computing the Pareto front of the largest software/hardware uncertainty patterns that a given RL is robust to (WP3). Extensive analysis including verification (WP2, WP3), simulation (WP2, WP3), and real-world experiments (WP4) will be carried out. The success of this project will greatly improve the practicability of RL in AD with a broader impact on other robotics applications.