University of Southampton

UKRI Gateway to Research · FY 2025 · 2025-08

Around 1 in 6 people globally are disabled: a figure set to increase due in part to the COVID-19 pandemic but also to military conflicts and ageing populations. Disabled people are a heterogenous group with a diverse range of impairment types and intersecting identities; and yet, they experience a range of similar economic, political, and social inequalities. Despite reporting high levels of interest in electoral politics, disabled people have lower voter turnout rates and are under-represented in legislatures around the world. To understand why these patterns occur, what barriers exist, and how to redress these inequalities, we need to study the relationship between disability and political parties - the key institution linking citizens and electoral politics. Political parties are important vehicles for mobilising and organising groups of citizens with an interest in politics; yet there are no studies focussed on how disabled people experience and perceive political parties, nor whether, when, and how parties think about disability, accessibility and inclusion. DISPOP fills that gap. Working with disabled people to co-produce our research, DISPOP aims to: (1) identify, analyse, and compare barriers experienced by disabled people, (2) map and evaluate existing party initiatives and best practices, (3) explore to what extent formal rules and informal norms render parties ableist institutions, and (4) co-produce recommendations with disabled people to make politics more accessible. DISPOP is a 4-year project with three inter-connected work packages (WPs) examining the different stages of the political participation journey: citizens to party members (WP1); members to activists (WP2); and, activists to candidates (WP3). DISPOP is a comparative project, comparing across countries and parties to identify whether, and how, different contexts and party characteristics shape disabled people’s experiences and perceptions, as well as the kinds of solutions parties might have developed. This approach will allow us to disseminate best practices and co-create meaningful strategies that enable parties around the world to become more accessible and inclusive. DISPOP will study the four largest parties in the UK, Denmark, Germany and Spain, selected to provide a degree of similarity and diversity within a limited geographical region. Our innovative multi-method approach includes survey data analysis, interviews, ethnographies, and document analysis. Bringing together political science with disability studies, and building on the PL’s (Evans) and Co-PL’s (Reher) novel and impactful research on disability and political representation, DISPOP will make original and significant contributions to our understanding of the ways in which disability shapes party political participation, as well as producing actionable recommendations and guidance to make democratic engagement accessible to a wider group of citizens. We will work with our Project Partner Disability Rights UK, the leading disability civil society organisation in the UK, to co-design and co-produce the research and co-create a suite of recommendations for improving and enhancing the accessibility of political parties. We will seek advice from our Advisory Board comprising Disability Rights UK, disability scholars, and party scholars from each country. Two Research and Innovation Associates (RIA1,2) will help undertake the empirical work, co-author outputs, and focus on impact and public engagement to help promote the findings of our work amongst relevant stakeholders. Providing mentoring and support for the ECRs is a core part of the project. DISPOP is underpinned by a commitment to creating an inclusive, ethical, and collaborative research environment that produces knowledge with real-world benefits.

UKRI Gateway to Research · FY 2025 · 2025-07

Aims and Objectives Aim: We seek to establish an EMIT Imaging “Xerra” cryo-fluorescence tomography (CFT) platform within an open access, core imaging facility at the University of Southampton (UoS) which specialises in multimodal, multidimensional, multiscale and correlative imaging and supports its users from project design to publication and dissemination. Objective 1: To satisfy unmet need to enable fluorescent markers to be localised in 3D within ex-vivo animal tissue with high resolution and sensitivity. Objective 2:  To bridge the significant gap in resolution, sensitivity and information potential that exists between our in vivo optical imaging systems and our high-end fluorescent microscopy systems. Objective 3: To make immediate and substantial impacts for multiple research teams from across the South Coast engaged in BBSRC’s strategic objectives, including its Advancing Frontiers of Bioscience and Tackling Strategic Challenges portfolios. Context CFT is a revolutionary new technology that combines the benefits of serial block face imaging with fluorescence imaging. It automatically carves thin slices away from the surface of deep-frozen biological samples (tissue, organ or whole animal – up to the rat size) and images each newly-exposed block face under multiplex fluorescence (with multiple exposure times for high dynamic range) and white light to detect fluorescently-labelling within its anatomical context with nM sensitivity and high resolution (isotropic 20-55 µm). Tomographic reconstruction converts slice data into 3D data, illuminating probe distribution throughout the entire sample with minimal sample preparation. The process can be paused to allow tape film to be applied to the block face, allowing the next slice to be recovered for downstream analysis. Currently CFT is only commercialised by one manufacturer (the EMIT Imaging Xerra), with a handful of systems installed globally in world-leading institutions. Introducing this technology to UK academia through an open access core facility has huge benefits. Research enabled CFT has immediate and wide application across Southampton’s bioscience portfolio for visualising and analysing fundamental biological process in health and disease including tumour growth and metastasis, angiogenesis, immune cell distribution and migration, brain drainage pathways, expression of fluorescent protein markers, analysis and optimisation of targeted therapeutics and drug delivery systems and detection of off-target accumulation and effects. Essentially anything requiring ex-vivo analysis of endogenous or applied in vivo fluorescence within small animals will benefit from 3D analysis with greatly-enhanced resolution and sensitivity.   Application and Benefits (1) Fostering collaboration and sharing of new technology: with only one (commercially-owned) Xerra installed in Europe (London), establishing CFT in an open-access university imaging core, has local, regional and national impact. Researcher co-Leads are drawn from four South Coast institutions to evidence the need. (2) Equipping the next generation: a core facility installation allows the widest range of undergraduate and postgraduate students, postdocs, early career researchers (ECRs), academics and Research Technical Professionals (RTPs) to benefit through mentored access, training, and ongoing advice and support from project design through to publication. This promotes transferable skills and CPD and enhances UoS’s many doctoral training programs, equipping research teams with expertise to drive innovative solutions and advances in biological and biomedical science. (3) 3Rs: although CFT samples come from animal experimentation, it maximises the information gathered from each animal in furtherance of the 3Rs. Data of a higher standard requires fewer animals to be statistically significant, thus CFT has the potential to reduce the numbers of animals used.

UKRI Gateway to Research · FY 2025 · 2025-07

Our project will use a powerful and only recently available geophysical technique to probe the interior of the hydrothermal system of an active volcano and thus gain unique new insights into how such systems work. Our target is Brothers volcano in the Pacific "Ring of Fire" about 400 km north of New Zealand. This volcano hosts one of the most active submarine hydrothermal systems in the world. It has been a focus for international study over the past two decades, culminating in scientific drilling in 2018 to recover samples and make measurements up to depths of nearly 450 m below the seafloor. Consequently it arguably the best-studied volcano of its type in the world. Hydrothermal fluids circulate in almost all volcanic systems, and this circulation is the main mechanism of chemical and heat exchange between the solid Earth and the oceans. Water sinking into the crust is heated by hot or molten rocks a few kilometres below the surface, then returns to the surface. Chemicals are exchanged with the rocks and can become concentrated in the rising fluids. Molten rock itself is an additional source of water and also gases. These fluids can vent vigorously into the ocean. As they cool and mix with seawater, the elements concentrated within them precipitate, sometimes forming large deposits containing metals such as copper and gold. Studies of the fluids, their deposits on the seabed and the surrounding altered rock have shown that: venting may either be focused or diffuse; vent fluids can have a variety of compositions, temperatures and origins; and the nature of the fluids can change as the volcano evolves. However, little is known about what lies beyond the few hundred metres depth range that can be accessed by drilling. Thus the shape of flow paths at depth and their relationship to the underlying hot or molten rock remain poorly understood. Our experiment involves using a powerful transmitter that sends electromagnetic waves into the volcano and measuring the resulting electromagnetic fluctuations using receivers on the seafloor and others towed behind the transmitter. Our measurements will be sensitive to the electrical resistivity beneath the seabed down to depths of several kilometres. Solid volcanic rocks have high resistivities, but rocks become much more conductive when they start to melt, resulting in a large contrast. Hot hydrothermal fluids are even more conductive, particularly when they are salty. Metallic mineral deposits at or close to the seabed can be more conductive again. Thus our proposed controlled source electromagnetic (CSEM) techniques can be used to image all of these features. Three-dimensional CSEM imaging is now feasible, and we will generate such images for the first time at a submarine volcano, thus achieving unprecedented resolution. We will use our resistivity image to estimate the size, shape, temperature and melt content of the heat source beneath the hydrothermal system; the temperature and salinity of the hydrothermal fluids and the shape of the pathways that they take within the crust; and the size and shape of the resulting mineral deposits. We will combine these images with results from international collaborators, including major new experiments involving sending sound waves through the volcano and further drilling and computer modelling of its evolution over time. Our results will show how the shape and internal structure of the heat source below and the faulting of the crust above that heat source drive patterns of hydrothermal circulation and thus the chemical alteration of the crust. This understanding can then be applied to other volcanoes where the subsurface structure is less well known. We will also determine the relative contributions of circulating seawater and fluids released from the heat source to the formation of mineral deposits near the seafloor, and work with partners in the mining industry to assess implications for exploration for such deposits now on land.

UKRI Gateway to Research · FY 2025 · 2025-07

Houses in the UK are frequently home to an assortment of unwanted companions, including rats, mice, bedbugs and wasps. Warming temperatures and changing pesticide responses are intensifying these infestations, and there is growing political, legislative, and ethical debate about how they should best be managed. Domestic infestations wreak economic damage and trigger psychological distress, but their effects are unevenly felt, rendering pests not just a public health concern, but also an issue of socio-economic injustice. While costly for some, infestations are lucrative for others, and the professional pest management (PPM) industry is rapidly expanding. Yet despite its significance for public health, its growing economic clout, and the vast scale of the routine animal suffering and death that is integral to its work, the PPM industry is largely absent from social science literature. Particularly lacking are analyses that address the lived impacts of domestic infestations for residents, the embodied expertise of professional pest controllers, and methods which allow researchers to explore the lifeworlds of the pests themselves. The PPM industry is also in urgent need of data that can address public misconceptions about pest control and highlight the social and economic significance of the industry's work. In response, 'Situating Pests: Impacts, Disgust, Expertise and Responsibility' (SPIDER) aims to: Advance ethically grounded and effective responses to pests. Establish the Project Lead as a leading early career scholar in human geography, providing them with experience of project management and research leadership, and springboarding them into the next stage of their career. SPIDER's research objectives are: To document the lived experiences of infestation and of working in PPM, including everyday challenges and decision-making practices To develop novel creative methods for representing and understanding pests' geographies of the home To critically evaluate different ways of killing and living with pests as unwanted others Using qualitative methods the project breaks new ground, interrogating animals' claims to urban space; the entanglement of care, killing and disgust; and the home as a site of encounters and conflict between species. Focused on the private rental sector in London as a case study, it combines interviews with affected residents, participant observation with PPM technicians, and experimental creative methods for mapping rodent movements and placemaking practices. Given the patterns of infestation recorded nationally, it will produce findings that are generalisable across the UK. SPIDER's scientific contributions will include three open-access journal articles (making empirical, conceptual, and methodological contributions respectively), leading to a proposal for a monograph that will advance interdisciplinary debates surrounding housing inequality, public health, and multispecies ethics. Wider public engagement will be achieved via designing and delivering schools' workshops themed around 'Ecologies of the Home'. Moreover, SPIDER will produce two detailed and accessible reports tailored to the project's primary external collaborators (a housing justice network, and a PPM association), addressing the collaboratively developed research questions. These reports will act as databanks of scientific evidence that the external collaborators can repurpose in their policy, advocacy, and education work to directly impact decision-makers. Consequently, SPIDER will indirectly benefit UK residents who experience infestations, through proposing clear recommendations for ethically grounded and effective responses to pests.

UKRI Gateway to Research · FY 2025 · 2025-07

Quantum Technology (QT) is a UK National Priority subject to over £3.5bn of existing and future strategic government investment. Quantum research is a UKRI Grand challenge across EPSRC, Innovate UK and the SBRI, with an emphasis on developing manufacturing processes and products that deliver quantum advantage from the laboratory to real-world applications. Many quantum technologies rely on enabling optical components, devices and infrastructure for the generation, manipulation, and routing of light for interaction with atoms and ions; this forms the technical basis for quantum sensors, quantum imaging, quantum networks, and quantum computing. Worldwide, there is an estimated $38.6bn of national funding in QT annually (Qureca 2023) across hundreds of quantum research groups, representing a $Bn market for optical components, most of which have yet to be standardised. Balancing the ability to rapidly prototype, change, and scale complex optical parts with sustainable manufacture is central to building a viable supply chain for QT-enabling components, achieving growth from bench-level demonstrators to commercial sales, and advancing the UK’s position within both the quantum and photonics global markets. Building on a decade of EPSRC capital investment, a solid technical foundation and track record of delivery to the quantum community, our research programme seeks to establish ultra-precision machining as the de-facto approach to scalable, sustainable manufacture of optical components for quantum-enabling technologies. Our project will address key manufacturing challenges posed by the photonics industry to remove known barriers to optical automation, including: automated on-wafer ultra-precision machining of optical quality facets to eliminate the labour-intensive handling, mounting, cleaning and inspection associated with chip-scale optical polishing; automated milling of millimetres-deep ultra-precise optical quality structures to avoid cleanroom and chemical-intensive etching processes and enable a new class of compact quantum atom trap components; and introduction of intelligent feedback and control of the machining system to enable continuous, unmanned operation while maintaining quality between tools and wafers. These represent critical processes required to achieve photonic back-end processing suitable for a scalable automated photonics assembly line. Critically, fabrication using semiconductor machining tools can be performed without the need for expensive, energy-hungry, chemical-intensive cleanroom processing. This is better for the environment, provides a better balance between prototyping and scalable processing for moderate-volume quantum devices, and represents a better route for every quantum start-up and SME to achieve complex optical components in-house without excessive capital investment.

UKRI Gateway to Research · FY 2025 · 2025-07

Metabolic activity of bacteria is linked with increased functionality, e.g. proliferation, production of host- and microbial community-relevant metabolites. We hypothesise that metabolically active bacteria are spatially stratified and interact more actively with the host to maintain homeostasis or when perturbed contribute to disease. Host-secreted compounds and nutrient gradients contribute to differences in microbial community composition and activity in different locations. This project aims at a functional understanding of the metabolic activity landscape of the intestinal microbiome in situ at an unprecedented resolution, i.e. on the single cell level. It addresses how metabolic activity of individual microbiota shapes the microbiota as a whole and its interaction with the host and its immune system during steady state and when disturbed, for instance due to inflammation. We will use in vitro and in vivo models of immune system-microbiota interaction to decipher how the adaptive immune system via production of mucosal antibodies affects metabolic activity of distinct commensal strains and vice versa. Thus, this project will help resolve the ecological and functional interactions within the microbial community, in potentially dedicated nutritional niches and with the host in the context of homeostasis and when perturbed in chronic inflammation. This interdisciplinary proposal brings together a team and collaborators with complementary expertise in microbial single-cell analyses techniques optimally suited to address this aim. Created knowledge will unveil new possibilities to manipulate the microbiome to support health, for instance by designing immune system-targeted interventions to enhance colonisation of beneficial commensals.

UKRI Gateway to Research · FY 2025 · 2025-07

Context Light microscopy is fundamental to biological research, with widefield and confocal fluorescence microscopy being primary techniques in cellular biology. These methods employ fluorescent probes to provide multichannel, multidimensional and functional information by tagging cell types, cellular compartments, organelles and biomolecules etc. However, spatial resolution is restricted by the diffraction limit of light microscopy (determined by the laws of physics) to approximately 200nm laterally (XY) and 600nm axially (Z), which is inadequate to explore the subcellular details vital for comprehending cellular functions, processes and dynamics, inter- and intra-cellular communication, disease mechanisms, and therapeutic optimisation. Over the past two decades, super-resolution microscopy (SRM) has emerged to overcome these limitations, offering access to the sub-cellular nanoworld. Initially confined to specialised laboratories due to technical complexity, some SRMs are now turnkey, with enhanced accessibility, user-friendliness, adaptability, and features, making them suitable for core facility deployment and for the study of diverse sample types. This benefits a wide scientific community across multiple research fields who require organisational and functional information at the nanoscale. SRM stands as the gold standard in fluorescence microscopy, and lack of availability at the University of Southampton (UoS) significantly impedes the advancement of research agendas. Research Enabled Stimulated Emission Depletion (STED) SRM reveals the nanoworld with resolution to 30nm (XY) and 100nm (Z), dramatically extending imaging capability for diverse samples including 2D and 3D cultures, tissues, embryos and organoids; live or fixed. It greatly extends research in diverse fields at UoS spanning biotechnology, neurobiology, immunology, respiratory biology, stem cells and regenerative medicine, ciliary function and microbiology. It addresses fundamental biological questions including (i) neuronal synapse networks, contributing to the understanding of memory, learning, and reaction mechanisms (ii) the role of autophagy in age-related visual degeneration (iii) mitochondrial function and dynamics in health, ageing and disease (iv) receptor clustering and its role in agonism of immunomodulators, (v) collagen supramolecular assembly and its effects on lung tissue biomechanics (vi) Structure and function of cilia in health and disease. All necessitate immediate access to nanoscale 3D imaging to reveal sub-cellular information and keep UoS at the forefront of UK biological research. Aims and Objectives Acquisition of turnkey 3D-STED SRM by the Biomedical Imaging Unit (BIU) at UoS, an open-access, imaging core facility specialising in multimodal, multidimensional, multiscale and correlative imaging, to address multiple, unmet research needs aligned to BBSRC’s strategic objectives. Its impact addresses BBSRC priorities within the Advancing Frontiers of Bioscience and Tackling Strategic Challenges portfolios, extending across and beyond UoS. It would immediately, positively impact a large, interdisciplinary and regional user base (> 50 groups). Applications and Benefits (1) Training the Next Generation: locating STED in an open-access core allows the widest range of undergraduate and postgraduate students, postdocs, early career researchers (ECRs), academics and Research Technical Professionals (RTPs) to benefit through mentored access, training, and ongoing advice and support from project design through to publication. This fosters career development and transferable skills and enhances UoS’s doctoral training programs, ensuring a robust talent pipeline equipped with the expertise needed to drive innovative solutions and advances in cellular biology. (2) Interdisciplinary research collaborations: a step change in image resolution fosters greater synergy by breaking down traditional biology/ physics/ chemistry boundaries and cultivates a dynamic research ecosystem which collectively addresses complex biological questions.

UKRI Gateway to Research · FY 2025 · 2025-07

The development of new enzymes can be greatly accelerated by the use of new computational methods. Our approach is inspired by the naturally occurring enzymes secreted by pathogens that specifically degrade human antibodies in order to “hide” from the host immune response. Such specific antibody degradation can be useful in both biotechnological and therapeutic settings, and so there is considerable interest in repurposing and developing more of these immune evasion enzymes. A notable example is an enzyme (named IdeS) from the bacterium Streptococcus pyogenes, which degrades human IgG antibodies and has been repurposed for clinical use in removing unwanted IgG-mediated immune responses during kidney transplantation. Proteases that target other human antibody subclasses, such as IgM, IgA and IgE, have also been discovered, and provide further potential opportunity to reprogram the immune system. The specificity of such proteases allows for their use in disease treatment, whilst avoiding significant off-target protein degradation, and enables their use as laboratory reagents for antibody manipulation and analysis. Currently the clinical use of these pathogen-derived enzymes is hindered by the prevalence of immunity arising from previous pathogen infections, which can limit their application to a single dose. Engineering novel enzymes would provide a greater toolkit of specific antibody-degrading enzymes, which would enable their more widespread use. The revolution in deep learning computational methodology has unlocked a new paradigm for protein engineering. Technologies such as AlphaFold and Protein MPNN unlock the potential for enzymatic redesign to overcome the limitations of immunoglobulin degrading enzymes. Protein redesign can additionally improve properties of native enzymes, such as stability at varying temperature and pH, immunogenicity and antigenicity (i.e. how the protein is recognised by the immune system). We propose to utilise an interdisciplinary synthetic biology approach to redesign existing natural biological systems for uses across human health. We aim to employ generalisable computational methodologies to engineer novel proteases with specificities for each human antibody subclass, whilst also addressing some current drawbacks of existing immunoglobulin-degrading enzymes. This proposal will also facilitate the knowledge transfer of these pioneering computational technologies, developed at the Institute for Protein Design (IPD; Seattle, Washington), to enhance the UK's capability for computational protein design. We will firstly use established structural biology pipelines to generate high-resolution structural information about each of these antibody proteases, and subsequently use this information to inform computational enzyme redesign. We will develop novel variants of the IgG-degrading enzyme IdeS for multi-use therapies in organ transplantation, IgA-specific proteases for use in IgA nephropathy, IgE proteases for allergy desensitization and IgM proteases for potential B-cell lymphoma therapeutics. The primary goal of this proposal is the demonstration of the broad applicability of these methodologies, with the potential to develop novel biotherapeutics. The proposal will additionally provide tools and resources of potential application to broad communities in the biosciences.  

UKRI Gateway to Research · FY 2025 · 2025-07

Sepsis is a poorly understood, complex condition, affecting those of all ages, whose progression is difficult to predict and whose outcome can frequently be fatal. With the possibility for rapid deterioration in a patient’s condition, early identification of Sepsis is essential to improve patient outcomes and improve post-illness quality of life. The objective of this proposal is to build an improved understanding of the clinical testing pathway for early identification of Sepsis and further evaluate the suitability of a clinically relevant test that enables rapid testing at the point-of-care (POC) to advise critical clinical decision-making when treating this condition in an Emergency Department (ED). To develop a genuinely game-changing test, it is essential to bring together the appropriate clinicians and technologists to pinpoint the various testing needs and limitations, and to then deliver an appropriate POC test. Therefore, the proposal aims to develop and sustain a strategic partnership between the investigators across the disciplines of photonics engineering, microbiology, and clinical medicine at the University of Southampton (UoS), University Hospital Southampton NHS Foundation Trust (UHS-NHS), National Microbiology Reference Laboratory (NMRL), Uganda and Sri Devraj Urs Medical College (DUMC), India. Through strategic placements of the UK-investigators, primarily the UoS-based Project Lead (PL): a laser-physicist, within the ED and associated testing laboratory of UHS-NHS, NMRL and DUMC, and the UHS-NHS-based Project Co-Leads (PcLs): an Intensive Care Consultant and a Consultant Medical Microbiologist, for a limited period within NMRL and DUMC, the proposal aims to build a better understanding to address an unmet challenge of configuring and delivering a sepsis-diagnostic, which is equally well-positioned for use in hospitals with different resources and infrastructure. A diagnostic that provides a rapid result delivers a potentially invaluable benefit of saving the lives of those admitted to ED with Sepsis. This invaluable training within different healthcare settings, especially an ED and the associated testing laboratory, will help the PL, as mentioned in the Call: ‘Gain skills and knowledge to answer a specific cross-disciplinary research question’ – rapid POC testing for Sepsis. ‘Understand the drivers for that research challenge and the context in which any solution would be deployed’ – triaging and early diagnosis in hospital EDs. ‘Better identify the healthcare challenges and clinical workflows’ – within ED and testing lab, ‘where EPS (-based PL) has the potential to lead to novel solutions’ - a rapid test for early identification of Sepsis and patient stratification into appropriate treatment units. ‘Broaden their (PL’s) awareness of the current state-of-the art in other scientific (clinical diagnostics) disciplines that are needed to address the research challenge’ – of developing a test routinely employable within hospital EDs for Sepsis. Similarly, the proposed short visits will enable the PcLs to, as stated in the Call: ‘Understand the drivers for that research challenge and the context (lower- and middle-income country, LMIC) in which any solution would be deployed’ – i.e., in comparatively resource-constrained settings of an ED at hospitals in LMICs. ‘Understand the social science and design factors (in a LMIC) that influence the adoption and use of healthcare technologies and patient concordance’ - in LMICs. Finally, both the above will facilitate to ‘strengthen or build new collaborations (between the UK-investigators and those in the LMICs) and carry out broader multi-centre research within health technologies with the collaborators’ towards the end-goal of tackling Sepsis.

UKRI Gateway to Research · FY 2025 · 2025-07

Advances in nucleic acid therapeutics have caused a paradigm change in drug design, shifting the focus from drugging proteins to targeting nucleic acids. With a better knowledge of RNA biology and improvements in nucleic acid chemistry, RNA modulation has become more viable. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are amongst the most promising tools for gene silencing. These are now being developed into therapeutics for a broad range of diseases, including metabolic diseases, cancers, neurology, and ophthalmology. ASOs and siRNAs also provide powerful tools for studying genome regulation and mechanisms of disease. Developments in nucleic acid chemistry have culminated in the recent approval of ASOs and siRNAs in the clinic; however, challenges associated with biodistribution, delivery, cell uptake, and toxicity, limit their efficacy and broader adoption. Whilst further improvements are needed, the chemical evolution of ASOs and siRNAs is inherently limited due to their requirement to be recognised by their cognate proteins (RNAse H or RISC respectively). Our overarching aim is to develop tools to convert promising emergent nucleic acids that are not compatible with these proteins into potent RNA cutting tools and gene silencing agents. We will investigate attaching synthetic "molecular scissors" to nucleic acids so that they cut target RNA independent of proteins. In a complementary approach, we will determine whether it is possible to recruit an alternative RNA degrading protein by attaching small synthetic tags. If successful, we will expand the arsenal of oligonucleotide-based approaches for RNA manipulation and provide powerful alternatives for gene silencing.

UKRI Gateway to Research · FY 2025 · 2025-07

Multiferroic materials (or multiferroics) are single phase quantum materials that simultaneously exhibit more than one ferroic property including ferromagnetism, ferroelectricity, ferroelasticity or ferrotoroidicity. Multiferroics are of great interest because their different properties may work together in different ways and lead to exciting new potential applications, if we could understand this better. For example, a multiferroic material where an applied electric field can switch on (or off) magnetic properties of the material (and vice versa) can be utilised to develop (1) low power neuromorphic memory devices or (2) integrated circuits where the multiferroic functions as both interconnect and logic component. Electronic devices formed from such multiferroics can exceed 100 times the energy e?ciency of existing technologies and can therefore contribute significantly to reducing our dependence on fossil fuels. Multiferroics are generally found with varying regions of polarity, known as domains. The interfaces that separate these domains are known as domain walls. Domain walls in multiferroics are 2D systems that can host functional electronic and magnetic properties which could find utility in a new generation devices due to their agility and spatial mobility, if we could better understand them. Before multiferroics can find significant utility in a device setting, a clear understanding of the materials behaviour at the nanoscale is needed. To better understand multiferroic materials I will use a technique called Bragg coherent diffraction imaging (BCDI). This is a form of x-ray microscopy that doesn't requires focusing lenses and can permit high resolution three-dimensional imaging where the use of conventional optics is not feasible. BCDI of materials at the nanoscale provides information on atomic displacements from equilibrium with sub-angstrom sensitivity and nanometer resolution. The ability that BCDI has to directly image in three-dimensions structural properties of materials at the surface and in the bulk will greatly aid our understanding of the kinetics of dynamic phenomena that are central to the development of next generation materials and devices. Thus far and in the original proposal, e?orts have focussed on understanding quantum materials before they are employed in a device setting. It was shown in the programme of the original proposal that BCDI is able to reveal domain walls and domain types in three-dimensions in a single multiferroic hexagonal manganite nanocrystal.  It was also shown that it is also possible to determine the spatial orientation of ferroelectric domains (relative to the lab frame of reference) in a single multiferroic nanocrystal using BCDI. In this fellowship renewal I will focus on in-operando Bragg coherent diffraction imaging of devices formed from a selection of multiferroic quantum materials. Emphasis will be placed on the study of devices where multiferroic materials form a functional component. Insight gained here will greatly aid our understanding of multiferroic materials in a device setting and will serve as a platform to develop next generation technologies based on such materials. The application of BCDI to the study of multiferroic materials and also devices can facilitate in enabling a wide range of next generation technologies that otherwise are inaccessible due to an incomplete understanding of their properties. This research proposal will be carried out in collaboration with Prof. J. Marty Gregg (Queens University Belfast), Prof. Dennis Meier (Norwegian University of Science and Technology), Dr. Daniel Porter (Diamond Light Source) and Prof. Paul Quinn (Ada Lovelace Centre).

UKRI Gateway to Research · FY 2025 · 2025-06

This project focusses on the diversity of the NERC community in the South of England (excluding London), where there is a complex picture of both ethnic and socio-economic diversity, and the intersections between the two.  It seeks to identify ways in which the University of Southampton (UoS) – as a core part of the South’s NERC recruitment pipeline - can increase diversity of students on undergraduate, postgraduate taught, and postgraduate research degree programmes that are relevant to NERC’s core remit.  We will focus on people of colour and those from low-income backgrounds, as these are two areas which are historically underrepresented in NERC degree subjects and are geographically complex in the South. Our three work packages will: 1. Reflect on our current position and desired end goal 2. Identify barriers to progression along the NERC pipeline from those underrepresented communities 3. Understand what support and interventions have enabled UoS graduates from NERC-remit programmes to succeed in a NERC-relevant career, be that in industry or academia 4. Develop and evaluate a series of interventions that could be used to increase the diversity of students on UoS NERC-remit programmes at undergraduate, PGT and PGR level 5. Develop KPIs to monitor the success of these interventions based on readily available, national datasets. The core project team will work in partnership with local schools and sixth form colleges, and UoS professional service colleagues, to the following outputs: A Theory of Change to enable increased socio-economic and ethnic diversity among UoS NERC students A method for HE institutions to monitor diversity within their NERC pipelines using national datasets An understanding of the demographics of UoS students flowing in/out of the NERC pipeline A report identifying barriers experienced by current and past UoS NERC-remit students from the target communities, and how these barriers were overcome Posters highlighting successful PoC and low-income background alumni, with an associated editable template that other HE institutions can use A report presenting a range of potential interventions that may increase socio-economic and ethnic diversity in the UoS’s NERC-remit student body The core team consists of academics, from ECRs to senior staff, as well as professional services staff*.  We will work in partnership with stakeholders both “downstream” and “upstream” of UoS along the NERC pipeline.  Downstream, we will partner with three local schools, each of whom bring experience of working with very different student bodies.  St George’s has a high proportion of English as a Second Language (ESL) students; this is used as a proxy for ethnic diversity. Bitterne Park is a large school, with a high number of FSM pupils.  Woodlands Community College has 50% of pupils eligible for FSM.  We will also partner with Barton Peveril 6th form college – they are one of the largest colleges in Southampton, yet have a lower overall ethnic diversity.  JBA Consulting and JBA Trust are our “upstream” partners; they are a key part of the wider NERC community, through PGR sponsorship and contractual work with the EA. *Note: the core team includes EP, as well as the Research Culture Manager in the UoS Research and Innovation Service, and two partners from the UoS Widening Participation team.  Because of the way the costings are set up in TFS, it was not possible to add them to the Core Team list below.

UKRI Gateway to Research · FY 2025 · 2025-06

All massive galaxies harbour a central supermassive black hole (SMBH). If the SMBH is fed at a sufficiently high rate, it can become extremely luminous. Many aspects of the accretion process that powers such active galactic nuclei (AGN) remain uncertain. Importantly, even though accretion (usually via a disc) causes SMBHs to gain mass, the process is inevitably accompanied by mass loss, often in the form of disk winds. However, the physical properties of these outflows – and even their basic driving mechanism – remain extremely poorly understood. This is a problem for two reasons. First, these outflows can significantly affect observations, impeding the construction of a reliable physical picture of AGN. Second, these disk winds are critical to our understanding of galaxy formation and evolution, since they provide a key “feedback” mechanism by which an SMBH can affect its host galaxy. In the absence of a sound physical understanding of these outflows, cosmological simulations currently incorporate this feedback via simplistic recipes, without accounting for variations with SMBH mass, accretion rate and metallicity. The fundamental obstacle to understanding AGN disk winds is that radiation pressure on bound electrons must be important: simulating such line-driven outflows requires complex radiation-hydrodynamics (RHD), in a regime where none of the standard approximations are valid. In particular, the treatment of ionization and radiation is critical to correctly estimate the wind driving forces. Over the last few years, we have developed a unique, state-of-the-art RHD code that implements the crucial physics. Our first benchmark simulations – for line-driven disk winds from accreting white dwarfs – have already revealed a huge problem with earlier, more approximate calculations: due to their simplified treatment of radiation, the kinetic wind power was overestimated by a factor of ? 2000. We now propose to tackle line-driving in AGN. Specifically, we will determine the parameter space, physical properties and observational signatures of line- driven disk winds by carrying out RHD simulations accounting correctly for ionization and radiative transfer for a wide range of AGN properties; implement additional physical processes that may affect mass loss in AGN, such as clumping, X-ray irradiation and large-scale magnetic fields; construct a new, physically motivated feedback recipe for cosmological simulations, accounting for the dependence on SMBH mass, accretion rate and metallicity. The proposed work will significantly improve our current physical picture of AGN. It will also drive progress in understanding the co-evolution of SMBHs and their host galaxies.

UKRI Gateway to Research · FY 2025 · 2025-06

Since their discovery, observations of the lighthouse-like rotating neutron stars known as pulsars have produced deep insights into fundamental physics, from superfluidity and the nature of matter at supranuclear densities to the most precise tests of strong gravity. Furthermore, by carefully timing an array of pulsars, international teams now stand on the precipice of making the first detection of the stochastic gravitational-wave background and opening up the low-frequency gravitational-wave spectrum. This proposal aims to build and apply a new hierarchical profile-domain timing framework with game-changing potential to better time and learn about pulsars that exhibit correlated changes in their timing and shape properties. We will innovate with state-of-the-art Simulation-based Inference to speed up inference by orders of magnitude and apply hierarchical recycling to enable us to phase-connect millions of pulsations. Our methodology will allow us to improve precision timing for pulsar timing arrays by modelling frequency and polarisation evolution and studying the white noise known as jitter. We will also study pulsar astrophysics, such as glitches, mode-nulling/switching, and timing noise, seeking to deliver new insights about the nature of neutron stars and their environments. Together with international project partners, we will study archival data from the MeerKAT Thousand Pulsar Array data set, the STFC-supported Jodrell Bank Observatory (JBO), Mt Pleasant Radio Observatory (MPRO) in Tasmania, and others. In the long term, this work will build the foundation for our group to contribute to analysing data from the forthcoming Square Kilometre Array (SKA), which will revolutionise the radio view of pulsars. Its unprecedented sensitivity and large field of view will enable an order of magnitude increase in the number of known pulsars and regular high-fidelity timing of a large swath of the population. Our project will succeed because we bring together domain-specific knowledge, a history of innovation across astrophysics, leadership experience, technical experts to overcome existing computational challenges, project partners with access and expertise on pertinent data, a passionate and involved supervisory team, and a supportive environment to foster the necessary creativity. Our project is important as we will develop a new approach to pulsar timing with game-changing potential to improve the resolution of pulsar timing arrays, generate new insights into neutron star astrophysics, and pave the way to grow Royal Holloway's new astronomy group and contribute to SKA science.

UKRI Gateway to Research · FY 2025 · 2025-06

Understanding the variability of the terrestrial hydrological cycle under climate change and other human impacts is crucial to predicting the future evolution of the water, energy and carbon cycles, and how to develop mitigation and adaptation strategies to reduce negative impacts, particularly of extremes such as floods and droughts. Soil moisture (SM) is the key state variable of the terrestrial hydrological cycle and controls the evolution of these other cycles. SM varies over a wide range of spatial and temporal scales (from metres to landscape scales, and from hours to interannually), driving complex interactions between cycles. However, our knowledge of this variability and its drivers is limited to a small set of field studies or coarse resolution (> 1km) and uncertain satellite and model estimates. This hampers our understanding of how the terrestrial hydrological cycle varies and how it will evolve in the future, and for a range of SM dependent applications. These applications include risk assessment and monitoring of hydrometeorological hazards (flood, landslide, drought, wildfire); carbon storage and natural resource management; mitigation of water-borne disease; and habitat conservation. The proposed research is therefore aimed at transforming our understanding of the variability of SM and its feedbacks with land- atmosphere processes, and the implications for applications. The project will innovate by bringing together cutting-edge modelling and data assimilation approaches, and multiple data sources, to answer 2 key research questions about our understanding of water- energy interactions at the scales of biophysical processes: What are the key scales of variability of SM across different landscapes and the drivers, and how do these drivers intersect to generate wet and dry extremes? This question seeks to know the scale dependency of SM variability, its drivers (e.g. soils, land cover/use, weather and climate) and their complex interactions. A range of processes (e.g. land-atmosphere energy and moisture transfer; biogeochemical cycling; surface-groundwater interactions) are known to be dependent on and feedback with SM variations, but our understanding is limited to small-scale, site-specific studies. How can improved representation of SM variability at process scales improve monitoring and prediction, and benefit SM dependent applications? A wide range of applications are dependent on SM, yet current approaches are generally based on coarse resolution and simple approaches, which limits their accuracy and utility. The research will develop novel, global datasets of high-resolution hydrological variables, based on innovative use of a “hyper-resolution” land-surface model constrained by satellite data. This will be the first dataset at such resolution globally that is physically consistent across variables. Statistical analysis methods and model experiments will be used to understand the spatio-temporal variability of SM and identify the drivers and feedbacks of variability and how these generate dry and wet extremes. We will apply this understanding to transform how data are used for SM-dependent sectors and applications, focussed on a co-developed case study on drought monitoring. The team is led by Prof. Justin Sheffield, who has a long track record of research in this area, publishing extensively on hydrological processes and extremes under climate change, and the application to hazard risk reduction, water and food security, and climate mitigation and adaptation. Working with international stakeholders, this research has been translated into benefits for a range of end-users, particularly in low/middle income countries, and has been recognised by several major international awards.

UKRI Gateway to Research · FY 2025 · 2025-06

How do pulsars form, evolve and behave? And how can we apply this to use them as precision tools to probe fundamental laws of physics and the invisible structures of the universe? These are the two key questions propelling my research. I am leading projects applying statistical physics to understand pulsar radio emission and map the structures of the interstellar medium (ISM), using the most sensitive radio telescopes in the world. Pulsars provide a key observational link to magnetars, X-ray binaries, and the unknown origins of Fast Radio Bursts: by understanding pulsars, we have important insight into a world of extreme and transient astrophysics. I will address the following objectives to achieve my research vision. I will investigate how pulsar radio emission evolves over its lifetime, using large-scale surveys with state-of-the-art radio telescopes to monitor the pulsar population over time, and make precision ISM measurements. I will apply machine-learning to identify correlations in polarization behaviour across the pulsar population, and develop a citizen science programme to classify vast observational datasets, building a connected picture of how pulsars evolve. Modern radio telescopes are generating ever-increasing volumes of data. My research is designed to derive the greatest benefit from this, by developing statistical techniques to understand the pulsar population and link this to neutron star theory. Through my international collaborative projects to study pulsars with the MeerKAT and Parkes telescopes, I have the experience required to achieve these objectives. I will apply my expertise in pulsar polarization, ISM measurements and analysis of large datasets to study the statistics of the pulsar population. By developing a machine-learning toolkit, and a citizen science project, for classifying pulsar polarization behaviour, I will publish the first full statistical model of the three-dimensional pulsar radio beam, and characterize how its behaviour evolves across the pulsar population. I will also create a catalogue of precision measurements of the ISM and use them to produce an updated map of the magnetic field of the Milky Way. Throughout, I will promote public engagement with science, both through citizen science, and through a school-focused outreach programme. My research is at the centre of a unique moment in pulsar astronomy: the Square Kilometre Array telescopes (SKA) are predicted to find every observable pulsar in the galaxy, opening up a new era of discovery. With extreme densities, intense magnetic fields and bright coherent radio emission, pulsars probe almost every branch of physics. Pulsars are tools for revealing galactic structure, testing the nature of gravity and searching for gravitational waves. We need to characterize the currently unexplained variability of pulsar radio emission to make progress with these important applications, and maximise the science achievable with the SKA. My results will form the scientific framework for the origins of pulsar radio emission, paving the way for using future SKA discoveries to test the laws of physics. My proposed research is designed to capitalise on modern computational and telescope technology to build a full statistical picture of the pulsar population. My work will advance the EPSRC strategic delivery goals of realising the benefits of AI, and improving society through engagement with science. I have the expertise, collaborative networks and technological capabilities to successfully address my research objectives: my research will ensure a significant advance in pulsar and transient science in the modern era of time-domain astronomy.

UKRI Gateway to Research · FY 2025 · 2025-06

Earth’s magnetosphere is driven by its interaction with the solar wind, and in particular by its response to the interplanetary magnetic field (IMF). The IMF is highly variable; the most important controller of the magnetosphere’s response to the solar wind is whether the IMF is directed “northward” or “southward”. In recent years, there have been a series of advances in our understanding of how the magnetosphere responds to periods of northward IMF, but overall our understanding remains poor. During periods of northward IMF, a “wedge” of magnetic field lines can build up in the nightside magnetosphere (the magnetotail), which is associated with a structure in the aurora (northern lights) called a transpolar arc. The “wedge” field lines are “closed”, i.e. connected in both directions to the planet, unlike higher latitude field lines in the magnetotail which are “open” (connected to the IMF). The “wedge” of closed field lines can grow to fill the magnetotail in a given sector; we have discovered that it can then interact directly with the IMF through a process called reconnection. This is an exciting discovery, because it means that the IMF then opens magnetic field lines at these latitudes, rather than simply “stirring” flux as is typically the case. Our proposed work will capitalize on these recent discoveries to develop a better understanding of the way the magnetosphere behaves when the IMF is northward. Specifically, we will: Determine the spatial extent of reconnection between the IMF and the wedge Determine the impact that the wedge plasma has on the lobe reconnection process Characterise “wedge” plasma structure three times further downtail than previously possible Investigate how the wedge evolves, once formed Test for upstream “triggers” of wedge events in order to provide valuable modelling constraints We will achieve these objectives by exploiting a large dataset of “wedge” events that we have developed, based on data from a spacecraft mission called Cluster. We will extend the spatial coverage of wedge observations by surveying data from a mission called ARTEMIS, which crosses the magnetotail much further downtail than previous wedge observations (most likely at a significant fraction of the distance downtail to the end of the wedge). Our investigation of potential “triggers” will have significance for the validity of magnetospheric models during periods of norward IMF. Collectively, these will provide a major advance in our understanding of how the magnetosphere behaves.

UKRI Gateway to Research · FY 2025 · 2025-06

The inspiral and merger of binary black hole (BBH) systems will continue to be prime target for gravitational-wave searches as we approach the era of third-generation and space-based observatories. The sensitivity increase and access to lower-frequency bands will allow us to see much further into cosmological history, probe BBH mergers with exquisite precision, and bring to view new types of merger phenomena. As detector sensitivity improves, so too must the accuracy of our waveform models, to minimise systematic biases in parameter recovery due simply to modelling error. And as detectors become sensitive to sources with a broader range of physical properties (mass disparity, eccentricity, spin configurations), our models must be extended to capture the new physics. Within this effort, a fascinating new technique has recently emerged, based on the study of BBHs in hyperbolic scattering. While scattering scenarios are not themeselves important sources of observable gravitational waves, they can provide a remarkably efficient handle on the general-relativistic dynamics in astrophysically relevant, bound BBHs. This is thanks to a remarkable "unbound to bound" mapping that has been discovered recently between certain orbital observables---e.g., one relating scattering angle to periastron advance. This mapping underpins the relevance of recent endeavours to apply QCD-inspired scattering-amplitude methods to the BBH problem. While remarkably successful, such calculations are primarily post-Minkowskian (PM), a-priori restricted to weak interaction. This we began to remedy in recent work by applying methods from self-force theory, with scattering observables now calculated in full General Relativity, albeit expanded in the BBH's mass ratio. Our exploratory work has already led to interesting synergies with Amplitudes calculations, and demonstrates how the validity of the latter can be extended to the strong-field regime through hybridisation with self-force results. Our aim here is to consolidate these initial explorations into a coherent programme to improve BBH waveform models using self-force calculations in scattering orbits. It has 3 interweaving strands. (1) Extend current toy-model analysis to the full BBH problem (without spin), calculating scattering observables through second order in the mass ratio. (This, as a by-product,  will give a complete description of the radiative dynamics at any mass ratio through 6PM order, well beyond current knowledge.)  (2) Formulate unbound-to-bound mapping in the context of self-force theory, and thus apply our results to bound BBHs.  (3) Use our results within existing BBH modelling frameworks---self-force, Effective One Body, Numerical Relativity---to improve the accuracy, speed, and parameter-space reach of current waveform generators.

UKRI Gateway to Research · FY 2025 · 2025-06

In March 2025, the hyper-arid Namib Sand Sea experienced a highly unusual and significant rainfall event.  At the Gobabeb Namib Research Institute, over 10 mm of rain was recorded in one day - the first such event since 2011 and the fifth-largest single-day of rainfall since records began in 1962.  These events are extremely rare, with only nine comparable episodes recorded in the last 60 years.   This unexpected rainfall provides an unprecedented scientific opportunity.  From 2018 to 2023, our NERC-funded research at Gobabeb investigated the initiation of sand dunes, focusing on how local surface conditions, particularly gravel plains, influence aeolian sand transport.  We demonstrated that gravel surfaces temporarily store sand and play a critical role in protodune formation.  However, our observations were limited to the region's baseline hyper-arid state, with no vegetation present.   This extraordinary rainfall will trigger a rapid but short-lived phase of vegetation growth, particularly grasses, across the very surfaces we previously studied.  This introduces a previously unobserved and ephemeral control on the aeolian sediment budget: vegetation.  The opportunity to study this ecogeomorphic feedback is both scientifically novel and time-sensitive.  The interaction between emergent vegetation, wind, and sand transport remains poorly understood in hyper-arid systems.  As climate change is predicted to increase the frequency of extreme rainfall events, understanding the potential role of vegetation in shaping and controlling sand transport pathways and dune system dynamics is both current and globally relevant.   Immediate action is needed.  Vegetation in this region responds rapidly to rainfall, and the seasonal onset of strong sand-moving winds in June will initiate active aeolian processes.  To capture the system in its dynamic transition phase, field data collection must begin without delay.  Gobabeb offers a uniquely controlled and previously instrumented site where both vegetative and sedimentary responses can be monitored in detail, making it the only viable location globally to conduct this kind of integrated study at this time.   Objectives Objective 1: Over a six-month period, quantify how spatial and temporal changes in vegetation growth affect: a) surface roughness, b) rates of sand transport, and c) protodune development. Objective 2: During individual sand-transporting wind events (lasting <1 day), measure direct interactions between vegetated surfaces, airflow, and sand flux.   Scientific Contribution This research will provide essential insight into the ecogeomorphic dynamics of hyper-arid dune systems.  It will enhance our understanding of how vegetation, when briefly present, modifies wind-driven sand transport and bedform evolution.  For the first time we will quantify the impact of this additional roughness element on the fundamentals of sand transport and dune initiation processes.  These findings will capture environmental drivers that inform models of dune development in both hyper-arid and semi-arid environments, contributing to improved predictions under climate change scenarios.  Furthermore, as vegetated dune systems may serve as transient carbon stores, this work may also have implications for global carbon budgets which are a critical and understudied contributor.  Capturing these rapid, ephemeral processes requires immediate and targeted field investigation - precisely the purpose of this urgency grant.  

UKRI Gateway to Research · FY 2025 · 2025-05

Light weighting is one of the biggest challenges facing manufacturers today and urgently required for next generation cars to increase fuel efficiency and reduce carbon emissions. Reducing a car's weight by 50 kg decreases emissions by up to 5g CO2/km and increases fuel economy by up to 2%. Being 75% and 33% lighter than steel and aluminium (Al), Mg is becoming more popular with automotive engineers. In theory, Mg alloys offer a promising solution for lightweighting in several industrial sectors. However, Mg components currently only constitute ~1% of a typical car’s weight. This is attributed to long-standing issues with Mg alloys such as high production cost, low formability and high corrosion rate, compared to heavier Al and steels. Therefore, designing high performance and low cost Mg alloys is in great demand for transport industry. Producing strong, formable, stainless and low-cost Mg alloys is recognised to be extremely difficult and has not to date been achieved. Traditional alloy design routes and manufacturing processing are not only time-consuming and not cost-effective, but also cannot guarantee production Mg alloys with high performance. In addition, the highly debated recrystallisation and deformation mechanisms, critical in optimising mechanical and physical properties of Mg alloys, need to be thoroughly explored and established. The overall objective of this fellowship is to develop new routes of alloy design, simultaneously developing innovative manufacturing processes, thereby producing strong, formable, stainless and low-cost Mg alloys(e.g., yield strength >300 MPa, Index Erichsen (I.E.) value indicating stretch formability >8mm, corrosion rate <0.4mg/cm2/day). This will be achieved by understanding how the alloying elements interact with each other and how the developed processes can be used to tailor multi-scale microstructures (e.g., alloys containing ultrafine grains (~1 microns) with weak texture). This fellowship will address significant challenges in coupling high mechanical properties and corrosion resistance within a single alloy system. The fellowship aims to help industrial project partners accelerate the development of new advanced light alloys. New thermomechanical/manufacturing processes are exportable technology and will permit companies to develop new IP. My research will be further extended to develop products for aerospace, public transport and medical industries and ensure a low carbon economy in the UK. Most importantly, this fellowship will assemble a new UK team of engineering and microscopists with the aim of turning vulnerable Mg into reliable structural/medical materials, thereby accelerating the pace of light weighting in several industrial sectors.

UKRI Gateway to Research · FY 2025 · 2025-05

High speed data communication underpins many important facets of modern life. High speed internet, online learning, high-definition video streaming, cloud computing, video conferencing, online gaming, artificial intelligence and the inner works of computers themselves all rely on the ability to transfer vast quantities of data at high speed. With the continuous introduction of increasing advanced and data hungry applications, the demand for bandwidth has grown relentlessly and is set to continue into the future. As data transmission rates increase so does power consumption and in some cases can dominate the power usage of the entire computing system. The growth of power use in the ICT industry is a major global concern with predictions showing that it could account for 20% of electricity usage worldwide and emit up to 5.5% of the world's carbon emissions by 2025. To support the growth in data demands it is of paramount importance that data communication technology is able to keep pace whilst minimising power use. Communication links are continuously being converted from working in the electrical domain to the optical domain since much more data can be transmitted optically with lower power consumption. The conversion is moving to progressively shorter links as the available technology becomes more cost effective and electrical bandiwdth limits are reached. Silicon photonic technology has been a key enabler of the conversion particularly in the data centre application space since the technology allows production of integrated photonics transceiver chips in a reliable, low-cost CMOS (Complementary metal-oxide-semiconductor) manner. Within the optical transmission link the process of converting electrical data into an optical format typically dominates power consumption. It is performed either by using an external optical modulator or by directly modulating the laser and for shorter optical links to be viable, their power usage must be reduced. For example, after almost two decades of research the performance of the silicon based optical modulator has manged to reach 100Gbaud with 1 pj/bit power consumption (including drive and tuning power), but power requirements for off chip and on chip links are ~100fJ/bit and 10fJ/bit respectively. For silicon photonic data transmission technology to meet these stringent energy and bandwidth requirements the hybrid integration of materials with stronger electro-optic effects onto silicon is essential as this will allow vast reductions in power consumption. In this proposal, we apply an advanced geometrically defined crystal growth process, tunnel epitaxy, to grow III-V semiconductors onto silicon photonic chips for use in a new-generation of optical modulation technology. The approach offers unique advantages in terms of footprint, yield, material quality and the ability to laterally grade doping levels during the growth process allowing precise optimisation of the trade-off between device bandwidth and optical loss. Combining the strength of the silicon photonics expertise at Southampton and the III-V on Si manufacturing at Cardiff, we will design and fabricate both external optical modulators and directly modulated light sources with state-of-the-art performance, targeting both short and ultra-short data reach applications. We will produce devices with 100Gbaud transmission with order of magnitude improvement in drive power which will enable the next generation of ultra short links to be viable. The developed technology will positively impact a large range of applications providing wide reaching societal and economic benefits.

UKRI Gateway to Research · FY 2025 · 2025-05

The RSE Metascience project aims to enhance the effectiveness of institutions' research and development by understanding the role of Research Software Engineers (RSEs) in computational and data-intensive methodologies across STEM, humanities, and social sciences. By leveraging initiatives like the International RSE Survey 2025, this project will gather and analyse data on RSE experiences and academic and code contributions, informing policy recommendations and best practices. Central to the project is the creation of the RSE Metascience Repository, a centralised resource designed to support evidence-based policymaking and understanding the impact of RSEs on research and development. By exploring the impacts of emerging AI code authoring tools on research software development, the RSE Metascience project aims to provide actionable insights and tools to enhance research quality, productivity, and recognition for RSEs worldwide. The RSE Metascience project will employ a variety of analytical methods to evaluate the contributions of RSEs and research software to scientific outputs. These analytics will include surveys, bibliometrics, and code repository analyses. The International RSE Survey 2025 will collect data on the global experiences, challenges, and perceptions of RSEs, providing a broad overview of their roles and contributions. Bibliometric analyses will examine the impact of RSE-authored publications and their influence on academic research. Code repository analyses will investigate patterns of software development, collaboration, and usage within platforms like GitHub, offering insights into the effectiveness of different development practices and the integration of AI tools. By combining these diverse analytical approaches, the project aims to generate a robust evidence base that highlights the critical role of RSEs in research, supports the development of best practices, and informs policy decisions. A key component of the RSE Metascience project is to influence policy and measure its impact on the research and development community. The project will produce policy briefs and publications aimed at disseminating findings and fostering dialogue between policymakers, research institutions, and the global RSE community. These activities will focus on advocating for structured career pathways, job security measures, and professional recognition for RSEs. Additionally, the project will provide empirical evidence to support resource allocation to RSEs, both in the UK and internationally, particularly by highlighting successful models from UK and German collaborations. The impact of these policies will be measured through their adoption, improvements in RSE job security, and the sustained use of the RSE Metascience Repository. By shaping policies that enhance the career development and recognition of RSEs, the project aims to strengthen the overall research and development landscape, ultimately bolstering the UK’s research capabilities and its leadership in global scientific initiatives.

UKRI Gateway to Research · FY 2025 · 2025-05

Metasurfaces are ultra-thin layers of artificial nanostructures that provide precise control over the propagation of light. In recent years, the field of metasurface technologies is rapidly progressing toward real-world applications. In this collaborative project, our two research groups at the University of Southampton (UoS) and MIT aim to co-develop metasurface technologies for next-generation automotive sensing. Our focus is on LiDAR (light detection and ranging) sensors, which are integral components in many automotive sensor suites. LiDAR sensors facilitate environment mapping in vehicles by utilizing a dynamically steered laser beam across a large field of view (FoV). Presently, this beam steering relies on a rotating mirror, but this solution is temporary due to its inherent challenges related to size, weight, power, and cost. In this collaborative project, our two groups will leverage our existing work on metasurfaces to develop a novel automotive LiDAR system devoid of any movable mechanisms. At the UoS, my research group has been at the forefront of coherent metasurface technology. The metasurfaces developed by my group are capable of dynamically deflecting a laser beam at varying angles. However, the current FoV is limited to approximately 10 degrees, significantly below the automotive industry standard. Simultaneously, the MIT group has pioneered fisheye metasurface technology designed for wide-angle imaging, offering an impressive FoV exceeding 170 degrees. In this project, our goal is to integrate and optimize these two metasurfaces on a single silicon photonics platform. The collective aim is to achieve complete solid-state beam steering with a substantial FoV of 120 degrees. If successful, our innovative LiDAR sensor could revolutionize automotive LiDAR technology, marking the first demonstration of metasurface-enabled, large FoV, fully solid-state laser steering compatible with the automotive industry. Utilizing a single channel of electronic control, our device has the potential to reduce sensor costs by approximately a hundred USD per unit, including savings in associated control and signal processing units. This breakthrough holds the promise of disrupting the current LiDAR market, providing significant technological and commercial benefits. It is poised to enhance the performance of modern advanced driver assistance systems, making driving safer and more economical, and expediting the advent of fully autonomous driving.

UKRI Gateway to Research · FY 2025 · 2025-04

MASLD (metabolic dysfunction associated steatotic liver disease) previously known as non-alcoholic fatty liver disease, is a rapidly increasing cause of chronic liver disease worldwide. It is strongly associated with the metabolic syndrome, which encompasses insulin resistance, obesity, hypertension and dyslipidaemia. A key complication of this condition is the development of hepatocellular carcinoma (HCC), which represents 80% of all liver cancers. Primary liver cancer is the fifth most frequently occurring cancer in the world and the second most common cause of cancer mortality (1).  In 30-50% of individuals MASLD-HCC arises in a non-cirrhotic liver (2–4), suggesting that there is a specific dysfunction of immune surveillance in MASLD.  I hypothesize that in MASLD NK cells are dysfunctional and this leads to reduced tumour immunosurveillance. The immune system has a key role in controlling tumour development.  An important member of the immune system are natural killer (NK) cells, which can respond to abnormal cells by either direct killing or recruiting adaptive immune cells to the tumour. They express a variety of cell surface receptors governing their response to surrounding cells and so can recognise HCC cells through multiple mechanisms. Previous work in the Khakoo group has identified that the family of NK receptors called killer cell immunoglobulin-like receptors (KIR) recognise peptides presented by HLA class and this leads to activation of NK cells and lysis of target cells (5).  Additionally HLA class I (HLA-E) is recognised by NKG2C and can lead to NK cell activation. However, there is limited understanding of how NK cells may function in the setting of MASLD-HCC. Studies have shown that NK cells in obesity (which is closely associated with MASLD) are impaired in their ability to respond to abnormal cells (6). I therefore aim to investigate the function of NK cells in MASLD and MASLD-HCC, and in particular how receptors for HLA class I impact the ability of NK cells to respond to cancer. My preliminary work has identified that the activating NK cell receptor NKG2C is significantly increased in patients with MASLD compared to healthy controls. Conversely, in patients with more advanced liver disease expression of NKG2C is reduced. NKG2C+ve cells can have enhanced anti-tumour activity and are associated with clonal expansions of inhibitory KIR-expressing NK cells (7).  My hypothesis is that NKG2C marks a subpopulation of NK cells important for the immune response to HCC. The aims and objectives are to: Compare the expression of a panel of activating and inhibitory NK cell receptors on NK cells from patients with MASLD, MASLD-HCC and healthy controls, focusing on the differences between NKG2C+ve and NKG2C-ve populations Identify key activating and inhibitory NK cell receptor:ligand interactions between MASLD NK cells and HCC using a panel of HCC cell lines Test the relevance of these interactions using co-culture with patient derived HCC organoids. This work will identify novel mechanisms by which MASLD NK cells are activated or inhibited by HCC, and their potential for treatment by immunotherapy.

UKRI Gateway to Research · FY 2025 · 2025-03

This proposal is focused on fibre lasers and will develop a new class of compact (centimetre length), narrow-linewidth (kHz and sub-kHz) fibre laser based on fibre Bragg gratings and Raman gain in silica-based fibres, the so-called Raman Distributed Feedback (R-DFB) fibre laser. This type of laser exhibits superior performance to those of standard rare-earth doped DFB fibre lasers in terms of efficiency, coherence length, low noise-level, and wavelength agility, and will allow for unconstrained single-frequency wavelength operation across the full transmission-window of silica. Continuous wave (CW) output power values up to 100mW will be targeted and the work will demonstrate R-DFB lasers in both germanosilicate and phosphosilicate fibres, each of which allows for different levels of Raman frequency shifts, at wavelengths applicable to LIDAR, high-spectral brightness and long coherence length applications incl., nonlinear optics applications, in particular four-wave-mixing (FWM), and spectroscopic sensing incl., trace sensing of targeted molecular species of importance for environmental monitoring. For ease of operation and integration, and for reduced complexity and cost, the work will also demonstrate direct laser diode-pumping of the developed R-DFB lasers. These lasers will help realise an increasingly important unmet need for low noise kHz linewidth sources in several wavelength bands where currently no such sources are available.