UNIVERSITY OF EDINBURGH

UKRI Gateway to Research · FY 2026 · 2026-02

Our economy is structured in a linear way, beginning with the extraction of resources and ending with waste. Such linearity is unsustainable – it exists at the expense of the environment and global justice. On the input side, the linear economy (LE) relies on natural resources – energy, water, raw materials – that are scarce. On the output side, our economy of consumption, destruction, and ever-faster renewal creates accumulation of CO2 in the atmosphere and growing piles of solid waste and landfills across the globe. Amongst the most promising responses lies the shift to a circular economy (CE). CE creates a loop between input and output by turning the latter into the former – either by maintaining or improving the usefulness of goods instead of discarding them (repair, upcycling, etc.), or by turning such wasted goods into resources (recycling). Law is crucial for such a shift, yet its role remain under-researched. Particularly, private international law (PIL), the law that determines jurisdiction in cross-border cases, their applicable law, and the recognition and enforcement of foreign decisions. Private law (PL) institutions – property, contract, employment and consumer law – shape the LE from creation to waste; PIL gives these institutions cross-border effects. PIL is tied to, and reinforces, the power imbalances of the LE within which it developed. Fast fashion (FF) provides a highly relevant case study to examine PIL threads in the LE and its rethinking for the just transition to CE. Many current practices in the global fashion industry are highly unsustainable. Fast- and ultra-fast fashion exacerbate these problems because of its super-rapid inventory turnover, low-quality goods, manufactured in countries with low wages and weak regulatory frameworks leaving workers and the environment unprotected. There is near consensus that transformation is needed. Circular economy (CE) models appear to have potential for the sector to foster sustainability without eliminating economic gains. They have started to gain traction on political agendas, industry practices, and regulatory frameworks. Pioneering CE business models in the fashion industry spanning from small local business in the Global South and the Global North to large global enterprises have shown the feasibility of such circularity for the industry. This project provides an analysis of the legal landscape for such a circularity transition. It explores the PL and PIL components of global value chains (GVCs) along the journey of textiles – from the places of production, via the marketplaces of consumption, to the places of disposal. FF relies on complex and fragmented GVCs. These GVCs span several countries and continents, economies and legal systems. The proposed study is the first of its kind in this field of crucial practical and theoretical importance. It builds on earlier studies of the PIs and Co-Is. Michaels/Ruiz Abou-Nigm/van Loon (eds.) (2021) established the role of PIL for sustainable development, including sustainable consumption and production. Ruiz Abou-Nigm and Sommerfeld (2024) provided the first in-depth analysis of circular fashion and legal design. Integrating empirical, analytical, comparative, interdisciplinary and doctrinal approaches, the study will provide a diagnosis of the PL/PIL impact on the fashion industry to contribute to a prognosis towards a more sustainable future for GVCs. This, in turn, will enable transformative rethinking of PL and PIL to enable the just transition to CE models.  

UKRI Gateway to Research · FY 2026 · 2026-01

Asthma is a variable chronic lung disease characterised by inflammation in the airways, resulting in heightened sensitivity to stimuli including allergens and irritants, causing wheezing, chest tightness, coughing and shortness of breath. Annually in the UK, asthma accounts for 60,000 hospital admissions and 1500 deaths. Despite the introduction of new therapies, there has been little sign of improvement in annual mortality rates. One major factor in this is poor adherence to the self-management and treatment regimen recommended by their healthcare provider.   The original BTS guidelines in 1990 not only emphasised the importance of ‘regular inhaled anti-inflammatory drugs’ but also stated that patients should ‘manage their own treatment rather than be required to consult their doctor before making changes’.  In contrast, in the subsequent 35 years, almost all assessments of adherence have measured doses taken compared to clinician prescription and ignored the evidence from the self-management literature that outcomes are better when patients are empowered to adjust their treatment in response to variations in their control.   The 2024 UK (and global) asthma guidelines further reinforce the inadequacy of the current simplistic concept of adherence (follow your doctor’s instructions) by recommending ‘as needed’ use of combined maintenance and reliever therapy (MART) regimens as first line treatment. However, individual interpretations of when medicine is needed can sometimes fall short of what is optimal for symptom control and mitigation of risk of crisis events. Researchers need to rethink their approach to assessing adherence to reflect supported self-management (flexible use of medication to maintain control of a highly variable condition) and support people with asthma to self-manage effectively.   Our PPI colleagues reinforced this approach:   “The question is not how do I stick to a routine, it’s how do I keep well?” -       Patient volunteer   We aim to explore the commonalities and differences in patient and healthcare providers perspectives of what it means to be ‘adherent’ to asthma medications, and assess how these definitions can be quantified objectively. The project plan consists of five components. 1.     A scoping review of adherence estimation methodology in flexible asthma regimens to identify previously utilised approaches to conceptualising adherence to self-management regimes.    2.     A survey of patients’ views on what adherence looks like to them.  This might include regular medication use, changing medication use relative to time-varying factors, self-monitoring, communication with their healthcare provider, making positive lifestyle changes, and more.   3.     Online interviews with both patients and healthcare providers, using findings from the survey, to explore aspects of patient behaviour that are related to the concept of adherence.    4.     Transform definitions proposed in the interviews into quantifiable definitions.  The feasibility of objectively measuring various proposed definitions will then be examined in four commonly used research data sources.    5.     Stakeholder engagement to create outputs towards greater research impact.   The primary output of this study will be a report highlighting the breadth of approaches to measuring ‘flexible’ adherence in a variable condition, and the corresponding limitations and barriers to meaningful ascertainment of adherence in routine data.  This will be used to update guidance on estimation and reporting of asthma medication adherence.  There may be synergies that can be drawn with other variable common chronic health conditions, such as Type-1 diabetes.  

UKRI Gateway to Research · FY 2026 · 2026-01

Wicked problems—complex, ever-evolving challenges like climate change, biodiversity loss, and public health crises—resist simple solutions due to their interconnected, contradictory, and dynamic nature. Addressing these issues requires transdisciplinary collaboration (working across multiple disciplines), systems thinking (understanding how different parts of a system interact), and engagement with diverse societal actors. While artificial intelligence (AI) has become a powerful tool in research ecosystems, its integration raises concerns about reinforcing narrow, incremental approaches rather than supporting the disruptive thinking necessary to tackle wicked problems. Disruptive science refers to research that fundamentally shifts perspectives on existing knowledge or creates entirely new paradigms, often rendering previous ideas obsolete. For example, the creation of the World Wide Web at CERN disrupted communication and research globally, enabling open access to information that transformed nearly every field. Michel Mayor and Didier Queloz’s identification of a planet orbiting a Sun-like star launched the field of exoplanet research. This work disrupted astronomy by shifting focus toward planetary systems beyond our solar system. This type of science is distinct from incremental research, which focuses on refining or improving existing knowledge without fundamentally changing it. Studies reveal a significant decline in disruptive science since the mid-20th century. This decline has been linked to trends such as hyperspecialisation (focusing narrowly on specific areas of expertise), pressure to publish incrementally (producing small improvements rather than bold breakthroughs), and reliance on large, structured datasets. AI tools trained on historical data often prioritise “safe” research pathways that align with established paradigms, sidelining risky transdisciplinary practices. This risks deepening intellectual silos (isolated fields of study), marginalising non-academic knowledge systems (e.g., Indigenous or community-based knowledge), and eroding critical skills like hypothesis generation and contextual interpretation. Funding structures incentivising AI-driven hyper-specialisation could further entrench these issues, stifling disruptive science and undermining progress toward global priorities such as the UN Sustainable Development Goals. This project investigates how AI reshapes scientific norms, collaboration dynamics and disruptive science in wicked problem research to provide actionable recommendations for funders. It will analyse trends within projects tackling wicked problems to determine whether AI tools prioritise consensus-driven outputs over pluralistic or contested knowledge in transdisciplinary teams. For instance, it will explore how AI specialists, domain scientists, and societal actors negotiate competing epistemologies (ways of knowing) and skill shifts—such as the tension between data curation (organising datasets for AI) and creative hypothesis generation—in AI-driven projects. Based on these findings, the project will propose funding recommendations for AI-based projects addressing wicked problems that incentivise “disruptive agility”. The methodology combines landscape mapping of funding databases—including UKRI and Horizon Europe—with ethnographic case studies of large-scale AI initiatives tackling wicked problems. This dual approach will identify emerging skills competencies, trends in impacts, career pathways, and patterns of AI use while capturing real-time collaboration dynamics. Realigning funding models to support transdisciplinary AI research can counteract the decline in disruptive science and create environments where risk-taking and systems thinking thrive. Our work suggests that we need a fundamental shift in how science is funded, governed, and practised, particularly when addressing wicked problems through AI-integrated research to create tangible, systemic interventions. Without such a shift, governments risk continuing large-scale investments in "grand challenges" that under-deliver—especially when AI is integrated using traditional methods. Crucially, it addresses systemic vulnerabilities in wicked problem research, contributing to long-term global resilience.

UKRI Gateway to Research · FY 2026 · 2026-01

Financial vulnerability represents a precarious state where individuals face substantial risks of economic hardship due to restricted access to resources, volatile income, and high susceptibility to economic changes. The concept varies over time and across individuals and groups, creating challenges for financial service providers in prediction and identification. When prevalent on a societal level, it can hamper prosperity and hinder national productivity. Traditional tools for detecting financial vulnerability are often inadequate as they do not take into account individual circumstances. The proposed fellowship seeks to address this challenge using a data-first approach. It aims to capture financial vulnerability by focusing on housing (mortgage and rents) and energy costs – two of the largest cost categories impacting UK households. It will exploit the effects of exogenous shocks on these costs to map how financial vulnerability evolves under the moderating influence of diverse demographic characteristics. These insights could then refine the offerings of financial service providers and adjust policy responses to prevent financial instability and increase resilience. Current methods of assessing financial vulnerability, such as liquidity ratios, debt-to-income analysis, and credit scores, often make incorrect assumptions about income consistency, uniformity of consumers, and resilience to external shocks. Therefore, the fellowship intends to scrutinise housing and energy cost shocks and develop a more responsive, granular understanding of financial vulnerability over time. The proposed empirical strategy involves merging the highly detailed proprietary financial transactions data from SDR’s FINDS, managed by the Smart Data Foundry (SDF) at the University of Edinburgh, with other non-proprietary datasets to characterise the moderating impact of unique demographic traits on financial vulnerability. The FINDS database provides pre-arranged access to anonymous, large-scale transaction datasets, covering up to 5.3 million individuals over extensive timelines. The analysis will draw upon advanced empirical modelling, which includes natural experiments to isolate the effects of a range of large scale and exogenous shocks, and machine learning techniques to predict future values of defined metrics. This cross-methodological approach intends to provide a comprehensive view of financial vulnerability and contribute meaningfully to better managing socioeconomic disparities and improving financial security and prosperity across the UK.

UKRI Gateway to Research · FY 2026 · 2026-01

Enumerative invariants appear throughout mathematics and mathematical physics.  They give a concrete way for us to tell objects apart: if two objects have different enumerative invariants, they are fundamentally distinct.  For example, the number of holes in a space is an enumerative invariant from topology that enables us to distinguish between a coffee cup and a glass.  In physics, BPS invariants are invariants of a space that determine the numbers of particles of different kinds predicted by the physical theory built from that space.  My research programme involves a mathematical formulation of these invariants called cohomological BPS invariants, which have found applications across a broad swathe of algebra, geometry and topology. Unlike traditional invariants that take numerical values, the values of cohomological are vector spaces; we can recover the enumerative invariants by computing dimensions of these vector spaces.  Reflecting the fact that the dimension of a vector space is never negative, cohomological BPS invariants have been used in the last decade to prove central positivity conjectures in algebra and combinatorics.  Furthermore, endowing these vector spaces with extra algebraic structure is expected to produce isomorphisms between different cohomological BPS invariants and thus equalities at the level of enumerative invariants, or symmetries between them.  Similarly, upgrading cohomological BPS invariants themselves to representations of basic Lie algebras should enable us to deduce very general results about the symmetries of enumerative invariants from the representation theory of those Lie algebras. The goal of this research programme is to fulfill this promise, and develop and exploit approaches to BPS cohomology that enable us to see beyond positivity results to a theory that explains these extra algebraic structures and extra symmetries in enumerative geometry and beyond. The foundational objective is to develop a new, more powerful construction of BPS cohomology and BPS Lie algebras, using a combination of quantum algebra and geometric representation theory.  This is a branch of algebra that is inspired by the study of quantum field theory, and which builds algebraic operations out of geometric ones. The research programme will have multiple applications to algebraic geometry.  For over thirty years, geometers have been developing theories of enumerative invariants in order to explain and prove startling predictions by string theorists regarding the counts of algebraic curves inside certain three-dimensional complex manifolds called 3-Calabi-Yau varieties.  In order to translate the physical theory into algebraic geometry, several extremely rich theories associated to these manifolds have been developed.  Many of the deepest conjectures in the subject posit equivalences between these mathematical theories, and symmetries within them.  A key application of this project will be to prove these conjectures using new foundations for BPS cohomology. The programme will also develop applications to understanding quantum scattering diagrams.  As well as being a fundamental tool in calculating scattering amplitudes in string theory, such diagrams are a central tool in cluster algebras and homological mirror symmetry,  bridging algebraic and symplectic geometry. By establishing enhanced foundations for the definition and study of cohomological BPS invariants this research programme will transform our ability to use ideas from physics, as well as powerful algebraic constructions, to uncover hidden symmetries of enumerative invariants and prove conjectures in a range of applications in algebraic geometry, representation theory, and beyond.

UKRI Gateway to Research · FY 2026 · 2026-01

Context: Cerebral small vessel disease (cSVD) is the commonest vascular cause of cognitive impairment and dementia (VCI/VaD, 20% of dementias), and commonly causes mixed dementia with Alzheimer’s disease, totalling some 45-50% of dementias. cSVD also causes 25% of strokes (‘lacunar’), frailty, loss of independence and accelerated brain ageing. It is often detected incidentally on brain scans. With no effective treatment, cSVD constitutes a substantial global unmet need. The challenge is to determine how cSVD causes brain damage, both directly due to damaged blood vessels and/or other indirect mechanisms, what factors drive cSVD progression, and how this can be stopped or reversed. Although cSVD associates strongly with hypertension, diabetes, smoking, intensive vascular risk factor management has had limited effects on stopping cSVD progression. Human brain magnetic resonance imaging (MRI) studies suggested an abnormality in cSVD in the small blood vessel lining (endothelium) and vessel wall that leads to leaky blood-brain barrier, poor control of blood flow, impaired fluid and waste clearance, and both ‘direct’ vascular and secondary ‘indirect’ brain tissue damage. Importantly, cSVD brain lesions can reverse spontaneously, leading to improved clinical outcomes, but which lesions, and whether secondary brain damage can be stopped, is unknown. In the LACunar Intervention Trial-2 (LACI-2), in 363 patients with lacunar (cSVD) stroke, two endothelial-stabilising drugs, isosorbide mononitrate (ISMN) and cilostazol, acting at different points on complementary vascular pathways, improved cognitive, cerebrovascular, and physical outcomes, with possible synergy. Our aims and objectives are to: track how cSVD contributes to cognitive decline and neurodegeneration visualised on brain MRI; use blood biomarkers to identify cells and pathways linked with clinical and tissue outcomes; determine if ISMN and cilostazol improve outcomes by reducing cSVD vascular lesion and/or neurodegeneration features; define biomarkers for cSVD, its brain tissue and cognitive outcomes; and inform clinical practice. Funded Phase-3 (NIHR LACI-3, n=1300) and Phase-2 (AlzSoc CVD-Cog, n=400; LACI-Cog, n=60) clinical trials, testing ISMN and cilostazol, in three complementary but distinct cSVD populations, incorporating pre-trial MHRA Scientific Advice, provide exceptional, cost-efficient opportunities to add, at marginal cost, strategic baseline and follow-up brain MRI and blood for biomarkers. This will enable us to investigate cSVD mechanisms and vascular- and neurodegeneration-stabilising interventional mechanisms using experimental medicine approaches. Reduction in cSVD lesion progression and secondary neurodegeneration with endothelium-stabilising drugs will strongly support that cSVD is due to endothelial dysfunction and secondary effects of dysfunctional endothelium respectively. Applications and benefits include: ISMN and cilostazol are off-patent and inexpensive; positive results could rapidly change cSVD/VCI/VaD clinical practice for a very neglected patient group, currently without effective treatment. Patients and public repeatedly state that stopping cognitive decline due to vascular disease is an absolute priority, hence a main motivation for the LACI cSVD trials. Increased pharma confidence in tackling cSVD/VCI/VaD, to identify novel drug-development targets. Provide biomarker diagnostics and prognostics for cSVD/VCI/VaD. Biomarker-MRI data will inform future vascular-neurodegeneration trials. Raise awareness of vascular mechanisms in neurodegeneration amongst UK and international neurodegeneration initiatives. Team: Wardlaw (PL); Bath, Quinn, Heslegrave (PcL); Cheng, Thomalla (PcL(I)); Thrippleton, Hernandez (PES); Woodhouse (specialist); Brown (grant manager); all highly experienced in cSVD, clinical trials, MRI, lead the project and contributing trials combining UK and German strengths in vascular-neurodegenerative disease and motivated sites with MRI and blood sampling capabilities; LACI-3, CVD-Cog, LACI-Cog participant panels will support the project; Industry partners (Alamar Biosciences, Capitainer) support biomarker studies.

UKRI Gateway to Research · FY 2026 · 2026-01

The Global Landscapes of Muslim Lives: Latin American and Caribbean Intersections examines the lives, histories, and linkages of Muslims in Latin America, the Caribbean, and their diasporas, exploring how their experiences reflect broader possibilities for understanding religion and its global futures. By focusing on the landscapes and infrastructures that connect local practices to transnational networks—migration routes, digital technologies, religious institutions, halal economies, philanthropic flows, and ecological, urban, and social environments—the project investigates how Muslims navigate and reimagine the conditions of belonging, identity, and faith. The following research objectives provide clarity and direction in achieving this overarching aim: To provide a comprehensive, multi-sited exploration of Muslim lives across Latin America, the Caribbean, and their diasporas. To investigate the dynamic relationship between local lives and global landscapes of exchange (ethnoscapes, mediascapes, ideoscapes, financescapes), with attention to the infrastructures and networks that shape these interactions. To survey and document diverse Muslim experiences through the collection of 75–100 semi-structured interviews and/or life histories with interlocutors across the region. To compare and analyze the lived experiences of Muslims across diverse geographic, communal, and socio-economic contexts, identifying patterns, divergences, and co-constitutive connections. To produce 15–20 detailed profiles of Muslim life in Latin America, the Caribbean, and their diasporas across the Americas and the Atlantic World (based on ethnographic composites or individual interlocutors), which will serve as the foundation for both scholarly and public-facing publications. To contribute to the study of Islam and Muslim communities in Latin America and the Caribbean through post-doctoral research opportunities, the organization of colloquia, and collaborations with the Latin America and Caribbean Islamic Studies Association (LACISA). To share results with scholarly and wider publics through: two academic gatherings (colloquia) co-sponsored by participating institutions and LACISA, public-outreach pieces in accessible venues (e.g., The Conversation, New Lines Magazine, The Revealer), the creation of an interactive “Americas Muslims Map” using ArcGIS StoryMaps or StoryMap JS, and the production of an edited volume or special journal issue (based on colloquia) and a co-authored monograph as the flagship project publication. Ultimately, this project seeks to demonstrate that the story of Islam today is not defined by a single center, tradition, or geography, but by the flows, connections, and creative adaptations that make Muslim lifeworlds across the Atlantic World simultaneously local, transnational, and global.

UKRI Gateway to Research · FY 2026 · 2026-01

We will address a major healthcare priority of epilepsy care for children at community level by developing a person-specific solution to detect and monitor childhood epilepsy.  We have identified this gap in our ongoing engagement with families and clinicians. Epilepsy affects over 50 million globally and around 600,000 people in the UK.  It is particularly common in young children, impacting neurodevelopment, education, quality of life and mental health.  It has potentially far-reaching consequences into adulthood through economic burden and disability.  There are major barriers to access healthcare, particularly the brainwave test needed to confirm the diagnosis and monitor epilepsy.  Currently, this test is available only in specialist centres and is heavily dependent on specialist clinicians. We will use Infantile Spasms – a severe form of childhood-epilepsy – as proof of concept to develop a transferable solution for early diagnosis and monitoring of treatment.  Infantile Spasms are characterised by: repetitive brief movements (spasms) within first year of life which are often misdiagnosed as far less serious conditions; excessive seizure brain activity which needs brainwave tests to confirm diagnosis; and frequent adverse neurodevelopmental problems, which improve by early treatment. Delayed diagnosis poses a huge burden on children, families, education and health services. The current approach to diagnose and manage Infantile Spasms requires 10 or more visits to a specialist unit for brainwave testing.  This poses an unfair time and financial burden on families and contributes to longer waiting times at the specialist units. Our team – composed of engineers, families and clinicians – will co-deliver a fair and equitable solution for person-specific early diagnosis, monitoring and prediction of response to treatment of childhood epilepsies.  Our solution will be applicable at home and community healthcare settings (GP, pharmacy...) and will improve patient outcome and quality of life. Our objectives are: To partner with families and clinicians to identify barriers preventing the early detection and management of childhood epilepsies in the community, and to co-deliver solutions to them. To co-develop methods to automatically and efficiently measure changes in brain activity due to early stages of childhood epilepsies. To co-create artificial intelligence methods that unearth robust relations between the brain activity measures and patient characteristics for more accurate and patient-specific management. To demonstrate that our solution reduces health inequalities by enabling the detection, monitoring and prediction of response to treatment in childhood epilepsies in the community. Our multidisciplinary team is uniquely placed to co-deliver our solution to childhood epilepsies thanks to our complementary expertise and ongoing stakeholder engagement, including our partners UK Infantile Spasms Trust and Epilepsy Research Institute UK, among others.  We will create exciting new advances on brainwave assessment and causal artificial intelligence, and integrate our tools into a portable device that will be piloted by families in the community. Our work will in turn enable more rapid access to treatment for children with epilepsy and related neurodevelopmental problems in line with Core20PLUS5, an NHS approach to reducing health inequalities for children that has epilepsy as one of its priorities, and the World Health Organisation intersectoral global action plan.  Our stakeholder engagement and grounding in causal methods will empower us to address issues of fairness and equity due to sociodemographic characteristics and yet unaddressed data biases head-on, ultimately improving quality of life for children and their families.

UKRI Gateway to Research · FY 2026 · 2026-01

While outbreaks of highly pathogenic avian influenza viruses (HPAIV) in Europe used to be rare and geographically contained, the  situation has dramatically changed in the last few years with thousands of outbreaks reported in domestic poultry and wild birds.  Despite being an intensive field of research, many unknowns remain as we are still struggling to predict HPAIV emergence, avoid viral  spread and limit the socio-economic impact entailed predominantly by control measures. Vaccination of domestic poultry against  avian influenza, is now being given full consideration, as it is becoming clear that traditional prevention and control approaches alone  will not curb the accelerating pace of occurrence of devastating HPAIV epidemics. On 1 October 2023, France became the first EU  country to implement a nation-wide vaccination campaign in ducks. However, vaccinating domestic poultry does not come without  important challenges. VIVACE therefore aims at putting together a doctoral network to contribute to fully integrate poultry  vaccination approaches into efficient management strategies for HPAIV. We will do so by unravelling the impact current and  upcoming EU vaccination policies will have on avian influenza virus evolution, surveillance and control strategies and societal burden  of HPAI. This will be done through a combination of disciplines from life sciences, epidemiology, computer sciences and social and  behavioural sciences. The training program proposed here includes scientific and transferrable skill sessions, builds on the integrated  added values of complementing expertise (virology, immunology, modelling, spatial and molecular epidemiology, social psychology,  economics and policy), and full access to state-of-the-art technologies in excellent environments. The consortium gathers 15  universities or research institutes and 5 private companies, securing both inter-sectoriality and wide geographic distribution with  tailored epidemiological and vaccination contexts.

UKRI Gateway to Research · FY 2026 · 2026-01

Regression models are used to describe the relationship between a response variable and variables that may predict it. In particular they allow the data analyst to specify the structure of the relationship, while estimating its exact form statistically. This interpretable structure is critical in many scientific applications where the models are used to test and refine understanding of mechanisms, and in industrial applications, such as energy forecasting, where it is critical to understand why a model makes the predictions it does. Originally the data analyst had to specify the structure of the relationship between the modelled variables with a rather restrictive degree of detail, making regression unwieldy or wholly unsuitable in many situations of moderate data complexity. In recent decades this restriction has been largely lifted, by the extensive development of methods and associated software for regression models to be specified much more flexibly. Models can be specified in the form 'the response variable depends on sums of smooth functions of one or more predictor variables'. This increased flexibility also increased the challenge of estimating models from data in a manner that is sufficiently computationally efficient, and sufficiently numerically stable, for routine applied use. It also introduced methodological challenges around the best way to represent the smooth functions from which models are built, and how to adapt standard statistical model selection and interval estimation techniques to the more flexible setting. The key issue is that once models are built in terms of smooth functions of variables, it is necessary to estimate 'how smooth' those function are. Doing this in a data driven way then has non-negligible consequences for other aspects of statistical inference. The applicant's work has played a substantial part in the development of a computationally general and feasible framework for this class of models. In particular the mgcv software package is a standard part of the R statistical computing language, and is widely used in science, medicine, government and industry as evidenced by over 50000 citations of the work and two REF case studies based on it. However further impact of this key UK based statistical infrastructure now requires three new developments. Firstly there is a need for better scalability across the full range of smooth regression models with substantial applied use. Currently excellent scalability has been achieved for univariate mean regression, but not for more general models in which response distribution parameters other than the mean are also important. Secondly, Python has become the language of choice for many modern data science applications in industry, for which smooth regression models would be key infrastructure. However the existing state of the art smooth regression methods are written in R and C (SAS have also implemented the methods), while the python support is very limited. A state of the art native python implementation is clearly required, leveraging significant methodological streamlining relative to the existing software and maximizing future impact. Thirdly recent developments in smoothness selection methods and numerical linear algebra offer a serious possibility of developing massively more efficient computational methods able to target dataset and model sizes far exceeding what is practical with current methods. All three of these developments would have immediate and long lasting industrial and scientific impact.  

UKRI Gateway to Research · FY 2026 · 2026-01

Translation is an extensively studied and fundamental cellular process that involves decoding mRNAs by ribosomes to produce proteins. Ribosome profiling (Ribo-Seq) is a hugely powerful and popular high-throughput tool for monitoring translation in living cells, revealing new mechanistic insights into translation regulation in diverse organisms. However, current protocols often involve lengthy optimisation and cell processing steps that can be plagued by artifacts. Given these technical challenges, there is a dire need for simpler and more robust ribosome profiling protocols. This motivated us to develop a chemical biology-based approach, which we have named Ribo-MaP, that could greatly simplify ribosome profiling across various model organisms. Our method uses chemical probes attached to well-characterised antibiotics that bind to the same site on the ribosome's decoding centre near the translated mRNA across all studied organisms. We employ these antibiotics as 'carriers' to guide reactive 'warheads' to chemically modify nucleotides associated with actively translated mRNA. The resulting nucleotide modifications can be readily detected and quantified using established high-throughput sequencing and bioinformatics approaches to generate snapshots of ribosome occupancy on mRNAs at nucleotide resolution. Thus, Ribo-MaP has the potential to revolutionise the field by offering a straightforward chemical 'tagging' approach that not only eliminates the need for complex cell processing and ribosome purification steps but also simplifies the entire process. By reducing the technical noise associated with other Ribo-Seq protocols, Ribo-MaP aims to enhance the robustness of ribosome profiling, making it more accessible and easier to implement for research groups studying gene expression. Moreover, the successful development of Ribo-MaP would enable us to address questions about translation regulation that existing Ribo-Seq methods cannot. Objectives: This 15-month project aims to generate proof of principle data to apply for larger-scale funding and patent applications. We will: Design and synthesise antibiotic chemical probes. Based on docking simulations on mRNA-ribosome structures, we will synthesise up to 10 antibiotic chemical probes that have the highest probability of modifying ribosome-bound mRNAs. Test compound reactivity. Translation inhibition and mRNA acylation activities of these derivatives will be tested in vitro using high-throughput cell-free GFP transcription and translation systems. The most promising reagents will be subsequently tested in cell cultures (human, bacteria, and yeast) to establish the optimal reaction conditions. Develop a basic bioinformatics pipeline for the analysis of the sequencing data: Using the preliminary sequencing data, we will establish a Ribo-MaP data analysis pipeline building on existing tools to process the raw data and quantify mRNA nucleotide modification frequencies. This will provide a robust foundation for developing additional machine learning and artificial intelligence approaches that extract biological insights from the data. Given that Ribo-Seq methods are used in drug discovery and offered as a service by companies, our approach is likely to have significant commercial impact. Hence, during the funding period we will also evaluate the intellectual property landscape for Ribo-MaP.

UKRI Gateway to Research · FY 2026 · 2026-01

Horizontal gene transfer (HGT)—the acquisition of genetic material from another organism without sexual reproduction—is recognised as being of great importance in prokaryote evolution, where it is responsible for the spread of antibiotic resistance genes among bacterial species. Its importance in eukaryote evolution has long been debated, with early studies erroneously inferring HGT because of contamination in reference genomes. Recent increases in the quality and quantity of reference genomes has led to well-supported examples of HGT of specific genes in particular species. However, the frequency and drivers of HGT, as well as the role that it plays in adaptation, remain unknown. This project addresses the extent and importance of HGT in eukaryotes using large-scale comparative analyses of flowering plants. Flowering plants are key components of terrestrial ecosystems, may experience more HGT than other eukaryotic groups due to features of their developmental biology, and now have sufficient genomes for comparative analyses at scale. We will perform the first systematic surveys of hundreds of high-quality plant reference genomes, allowing us to characterise the landscape of HGT within genomes and across species. We will also perform focused studies to understand HGT dynamics at the population scale, both in species with contrasting reproductive attributes, and in parasitic plants, where HGT may be most common and have the clearest link to adaptation. Overall, we will address the following questions: What is the frequency of HGT across flowering plants? How do genetic, reproductive and ecological factors influence HGT? What are the dynamics of HGT in parasitic plants? Our findings will examine an evolutionary process that may play an important but underappreciated role in facilitating adaptation. We will gain insights at a range of spatial and temporal scales, allowing us to investigate both broad patterns and detailed processes. By looking across hundreds of species, we avoid the idiosyncrasies of individual taxa and can generalise across flowering plants. Our results will provide key baseline estimates, allowing comparisons to other groups such as animals and fungi, and data to develop new theory. Case studies in parasitic plants will show the extent that foreign genes invade parasite genomes, revealing host specificity and adaptive HGTs that may be targets for control measures.  

UKRI Gateway to Research · FY 2025 · 2025-12

Hyaluronic acid (HA) is a naturally occurring polymer which is important for human health and development. HA is found in the synovial fluid of joints, the skin, and the vitreous humour of the eye. The length of the polymer and the ability to absorb water make this compound an excellent biological lubricant.  HA has numerous commercial applications, for example, in cosmetics as a hydrating agent and dermal filler, and in ophthalmic surgery to replace vitreous material lost during cataract lens replacement. The mechanical properties of HA are also used to supplement loss of synovial fluid in osteoarthritic joints. These varied uses make HA a high-value biomedical product with a multi-billion pound market value. Eukaryotic HA can reach a molecular weight (MW) of up to 14 MDa. The MW of HA is key to its mode of action wherein the higher the MW, the greater its efficacy in relevant biomedical procedures e.g. cushioning effect following injection into arthritic joints. Current manufacturing processes use fermentation of wild type bacterial species that naturally synthesise HA. This approach limits the MW of HA that can be produced, with the current market dominated by HA with a MW of approximately 3-4.5 MDa. Some specialised  biomedical applications require HA with a much higher MW, this is achieved by chemically cross-linking smaller polymer units to generate a higher MW product, which adds costly chemical processes and clean-up procedures into the manufacturing process. Addition of cross-linking chemicals can also cause adverse reactions in patients. We have used an engineering biology approach to build a platform technology which allows production of HA up to 7 MDa and a 33-50-fold increase in yield within the laboratory environment (0.5L scale). We have recently completed a small scale up assessment using a 5L fermenter which indicates the process is scalable. Together, our technological advances provide a potential advantage in a global market which could place the UK at the forefront of HA manufacturing. This will provide better biomedical products at lower cost and with greater patient safety. The goal of this project is to de-risk our platform technology for commercial deployment through two specific goals: 1) Further develop our proprietary bacterial strains to establish industrially robust, high performing strains with enhanced HA production, and 2) Develop a fermentation scale-up process to validate production as the next step in creation of a ‘spin-out’ company.

UKRI Gateway to Research · FY 2025 · 2025-12

Accurate preparedness and response are essential to saving lives in emergencies. Key components of enhancing safe response are understanding how and why the public respond to emergency instructions and embedding this knowledge into training for first responders and computer simulations used to plan response strategies. In Phase 1 of the Future Leaders Fellowship, we established that the phrasing first responders use when giving the public instructions can be used as a tool to improve safety because it impacts how the public view the responders and subsequent willingness to follow their instructions. Specifically, we found that the phrasing predicts how much the public feel part of a group with the responders, which is then associated with how fairly the public feel treated and their trust in the responders to safely manage the emergency. Crucially, this impacts how willing the public are to follow instructions from first responders in evacuation contexts. We established links with prominent stakeholders in first responder training, policy and guidance to identify routes for impactful change to first responder communication practices, as well as the pressing issues for responders and evidence needed over the coming years. Moreover, we implemented the effects of the phrasing used in first responder instructions on group dynamics into an agent-based model to improve the accuracy of evacuation simulations. This state-of-the art open-source model is firmly embedded in evidence from our psychology experiments and places the effects of first responder communication strategies on social processes into evacuation simulations for the first time. We are now working with international crowd modelling developers to implement this model into their software used globally for emergency planning. We are now poised to accelerate and expand the research agenda to maximise our impact. The renewal phase of the fellowship will focus on three key objectives: Adapting the phrasing of first responder instructions. We will identify how the phrasing used by first responders when giving instructions to the public impacts public response. We will focus on emergency scenarios that are classed as significant and most likely for the UK. We will ensure that the phrasing is accessible for the most vulnerable populations in emergencies, thereby increasing the generalisability and applicability of the findings. Continuous development, validation, and spread of the agent-based model. We will establish structures to continually update our model as new evidence is obtained and ensure the model can be integrated into existing software to maximise uptake. Updating first responder guidance, training and policy. We will work closely with leading first responder organisations to translate our research findings into tangible changes to first responder training, policy and guidance regarding communicating with the public, to improve safety in emergencies.

UKRI Gateway to Research · FY 2025 · 2025-12

Context: Climate change is increasing the frequency and severity of extreme weather events—primarily droughts and floods—which are dominant stressors in agro-ecosystems of East African drylands. These extreme events are driving increases in acute and chronic food and nutrition insecurity. Such shocks are key drivers of livestock mortality, acute malnutrition, and chronic poverty among pastoralist communities in the region. The Challenge the project addresses: While several different early warning systems provide forecasts for the drylands of East Africa, the use of these services is limited among pastoralists (<3% regularly use the services) but the potential value is high. Increasing evidence indicates a mismatch between the communication needs of pastoralists and modes and content of existing early warning systems as a chief barrier to greater use. Currently, organizations, such as the National Drought Management Authority (Kenya), produce forecast bulletins with lead times, frequency, resolution, language, and content all geared towards the needs of government and non-government decision makers. Thus, few pastoralists can understand the language used in those bulletins, it is also not clear that the information provided in the bulletins is actionable by pastoralists. This is because most early warning systems are developed through top-down approaches that overlook the traditional knowledge of local actors which weakens the cultural relevance and perceived accuracy of scientific forecasts. Aim: Following the agricultural innovation systems (AIS) concept this project will bridge the gap between the needs of pastoralists and the communication of formal early warning systems by addressing the following objectives: bring together an interdisciplinary group of stakeholders, scientists and pastoralists to co-develop knowledge through a weather information service from the bottom-up.  use social network analysis to understand information flows between pastoralists, allowing for heterogeneity in needs across individuals and communities as a foundation for the co-design process, and; adapt and blend information from existing early warning systems to meet those needs using human-centred design for the sharing of information.  Potential benefits: The project pushes innovation in several domains including, (1) bridging the gap between information conveyed using technical conventions and traditional modes of diffusion among indigenous people, (2) researching and leveraging existing communication networks and information flows, and (3) developing low-cost strategies to receive feedback from stakeholder communities which can be used in improving the value and contextualisation of weather information. The project applies human-centred design to ensure innovation is rooted in local needs and realities. We will cycle through stages of discovery, co-creation, testing, refinement, and deployment. A potential application of the work is to show that co-production methods can ensure the needs of pastoralists remain at the centre of climate-services which in turn will improve the usability of existing weather services so that pastoralists can better prepare for coming drought and flood. This leads to a?further benefit in improving pastoralist resilience and reducing acute malnutrition caused by weather shocks. This final application of the research will be to develop a framework for others working to provide information services to pastoral populations.

UKRI Gateway to Research · FY 2025 · 2025-12

The rate of loss of ice from the Antarctic Ice Sheet has tripled in the last three decades, and is expected to continue increasing – potentially leading to several tens of centimetres of sea level rise by 2100 – with important implications for planning and adaptation in coastal communities, particularly in the Northern Hemisphere. These losses are largely attributed to increased ocean-driven melting of floating ice shelves, which causes fast-flowing outlet glaciers to speed up. Warming oceans could further increase this melt under climate change, so it is critically important that models deliver credible assessments of the ice-sheet response to different greenhouse-gas emissions scenarios. A major limitation arises from the wide disparity in responses of current ice-sheet models to future climate warming. This disparity is due in large part to uncertainty in ice-sheet models’ representation of the current ice state, owing to ice sheets’ long memory of past changes. It also arises from uncertainty in how the future melting of ice shelves responds to ocean warming, and poor knowledge of key physical processes which ice-sheet models do not fully resolve. The key advance of this project will be to reduce uncertainty in 21st century ice loss from Antarctica through (i) next-generation assimilation of satellite observations into ice sheet models and (ii) advanced climate downscaling through high-resolution ocean simulation. This will be achieved through the following objectives: Improve Ice-sheet Data Assimilation to capture the current dynamic state of Antarctic glaciers and reduce model uncertainty. Improve model representation of poorly constrained ice processes by leveraging the results of assimilation. Develop an effective modelling treatment for ocean-driven melt through high-resolution simulations. Improve projections of 21st century sea-level contributions through coupled modelling of dynamic Antarctic glaciers under greenhouse-gas emission scenarios. We will, for the first time, produce 21st century projections of ocean-driven ice loss from Antarctica that are consistent with the full range of satellite observations of ice-sheet thinning, ice-stream acceleration, and ice-shelf melt. By focusing on regions in West and East Antarctica with the strongest thinning rates and oceanic forcing, we will greatly reduce uncertainties in century-scale ice loss and provide step-change improvements in ice-sheet data assimilation and ice-ocean modelling to the Antarctic modelling community. The proposed contributions are both novel and timely. The modern satellite record offers an ever-growing wealth of information on ice-sheet evolution, yet most ice-sheet models remain incapable of integrating it. In the Ice Sheet Model Intercomparison ISMIP6 (part of the Coupled Model Intercomparison CMIP6), most models did not reproduce the observed ice loss, and ice-loss forecasts had a incredibly wide range. Our preparations for ISMIP7 will commence shortly. BISTO will provide methodologies of how to formally constrain ice sheet models to match the observed ice loss, and demonstrate the impact on ice-sheet forecasts and their uncertainty. Many leading climate modelling centres are developing interactive ice sheets and ice shelves in their modelling frameworks. However, they face issues of resolution (due to the small-scale ocean processes under ice shelves) and initialization (due to the long time scales inherent in both ocean and ice sheets and the tight coupling between them). The objectives of BISTO will provide roadmaps for these large-scale ice-ocean coupling efforts, greatly improving societal capacity to project future sea level rise.

UKRI Gateway to Research · FY 2025 · 2025-12

Gambling harm is a growing public health concern, yet the evidence base remains fragmented and siloed. Research has tended to examine single factors such as mental health, socio-economic status or gambling availability in isolation—without considering how these intersect to compound vulnerability. Evidence shows harms are unevenly distributed: people in lower socio-economic groups, neurodiverse individuals (particularly those with ADHD or autism), and minority ethnic communities are disproportionately affected, often in combination with co-occurring substance use or mental health conditions. Structural drivers, including venue density in deprived areas and the expansion of online gambling, intensify risks, while temporal patterns of play, family dynamics, and gendered or cultural contexts remain underexplored. Recent qualitative studies highlight that gambling harms rarely occur in isolation and are embedded within wider adversities such as trauma, homelessness, and inequality. Despite these insights, there is no systematic synthesis that addresses how overlapping vulnerabilities and cumulative risk shape gambling harms. The field of gambling research has been dominated by studies that rarely prioritise the perspectives of those directly affected by harm (Sweet, 2025a). This review will place lived experience at its core, ensuring that the voices of people with firsthand experience shape the process from the outset.

UKRI Gateway to Research · FY 2025 · 2025-12

Nature is fundamentally important to people’s lives: supporting their mental and physical wellbeing, holding stocks of natural capital which underpin our economy and society, and serving as a source of inspiration and meaning. The UK’s international agreements and national policies commit to increase and enhance people's relationships with nature, and policy-makers, environmental planners and civil society organisations (CSOs) increasingly prioritise the measurement, monitoring and understanding of those relationships. Metrics of people's engagement with nature also form part of reporting commitments under international agreements such as the Kunming-Montreal Global Biodiversity Framework (GBF). To date, however, relevant data are far from harmonised. Surveys on people-nature relationships are currently conducted by multiple organisations and analysed separately. For example, devolution has led to data being gathered by different public bodies in England, Scotland, Wales and Northern Ireland and numerous environmental CSOs commission surveys to support their work. Together, these data constitute a rich resource with the potential to make important contributions to environmental policy and management, but the survey instruments used differ in their aims, content, design and implementation, and conceptualisations of the people and nature relationship. This limits the compatibility and sharing of data, constraining the insights and meaningful analysis that could be gained from a more comprehensive and collaborative approach, including answering UK-wide questions about people and nature relations. This timely project aims to combine existing survey data resources to create a new, harmonised multidimensional dataset concerning people’s relationships with nature across the whole of the UK, and use it to address priority questions for policy-makers. Work towards this goal will be organised into three work packages, which will: Map the scope, purpose and methodological details of existing surveys covering people’s relationships with nature, develop a robust process for combining them, where appropriate, and produce a harmonised dataset covering the whole of the United Kingdom Use the harmonised dataset to examine engagement with green space across the UK, in order to inform the development and delivery of UK policy and also support monitoring of international environmental commitments under the GBF Assess the potential for our approach to be replicated outside the UK, to permit comparative work on existing relevant data sets internationally. Our proposal has been co-produced by a partnership of academics, government and CSOs and will open-up new areas of research with direct societal impact. Within the project we will use the harmonised data to study determinants of engagement with nature, to evaluate policy based on comparisons across the four nations of the UK, and to examine whether current indicators are fit for purpose. Beyond this, the harmonised data will serve as a resource for the wider research community, the project will improve collaboration between organisations that currently collect data on people’s relationships with nature and identify areas of synergy and redundancy within their work. We will share our findings and lessons-learned widely within the UK and internationally, ensuring that the data and approaches are visible and accessible to a broad range of potential users and engaging key stakeholders through workshops and reports to promote best-practice for survey-based approaches to measuring engagement with the natural environment.

UKRI Gateway to Research · FY 2025 · 2025-12

When animals and plants produce eggs or sperm, their matching chromosomes pair up and exchange large segments of DNA via chromosomal “crossovers”. This is known as meiotic recombination, and it is a fundamental part of sexual reproduction. Recombination is beneficial: it ensures the correct number of chromosomes are transmitted into eggs and sperm; it also brings together beneficial gene-copies (“alleles”) onto the same chromosome, allowing populations to purge harmful mutations and respond faster to selection. However, recombination is also costly: too many crossovers can introduce harmful mutations, and can break apart beneficial alleles that are already linked together. These trade-offs were thought to constrain recombination rates to a narrow range. In reality, we see a huge diversity of recombination rates in nature: they differ within and between species, individuals, chromosomes, and even chromosomal regions. Understanding how and why this variation has evolved has important implications for evolutionary biology, fertility research, and animal and plant breeding. Yet, despite a century of theoretical attention, the evolution of recombination rates remains a major unsolved question in biology. Females and males often have very different rates and patterns of recombination, a phenomenon known as “heterochiasmy”. Recombination rates can be higher in females (e.g., in humans, deer) or males (e.g., in sheep, macaques), and this can vary along the genome, with female- or male-biased recombination “hotspots”. There are many evolutionary theories to explain heterochiasmy, but none are supported with real-world data. A major oversight is that theories rarely consider the molecular basis of female and male recombination - they occur in different tissues (ovaries and testes) at different times of development, are controlled by different genes, and have different effects on fertility. Therefore, if we want to understand the evolution of recombination more broadly, we must first understand the molecular causes and evolutionary consequences of variation in females and males. Our team will investigate this question using genomic data from a long-term study of house sparrows (Passer domesticus). Female sparrows have more crossovers than males, but recombination can be female- or male-biased along the genome. We hypothesise that when DNA unravels to transcribe and express genes, meiotic proteins use this window of opportunity to bind to the DNA and form crossovers. Therefore, differences in gene expression and DNA “accessibility” during meiosis may be a mechanism to explain why heterochiasmy is so common. Furthermore, if some genes are only expressed in meiosis in one sex, we hypothesise that these genes will be less constrained to the other sex, meaning they can evolve faster and lead to rapid evolution of heterochiasmy. Our project will use newly-emerging and cutting-edge sequencing technologies that quantify gene expression and DNA accessibility within individual meiotic cells in both sexes. First, we will determine if sex-biased recombination hotspots correspond to regions of high expression and accessibility in their meiotic cells. Then, we will identify genes that have similar or different effects on recombination between the sexes, and determine if those that are different show evidence of faster evolution in their DNA sequences. Our innovative study will be a first direct examination of the molecular causes and evolutionary consequences of heterochiasmy. It will greatly improve our understanding of a fundamental biological process that is crucial to fertility and inheritance, and broaden our knowledge of the factors that affect recombination rate evolution in nature.

UKRI Gateway to Research · FY 2025 · 2025-12

While literacy (reading and writing) is associated with numerous benefits, literacy engagement among young people is at an all-time low, underscoring an urgent need to better understand the factors that drive literacy and leverage this understanding to reinvigorate young people’s literacy practices. Poetry – a relatively low-time-investment/high-emotional-payoff literary form – uniquely overcomes many identified barriers to young people’s literacy. But is poetry being offered to young people in effective ways? Advancing the Fellow’s innovative creative practice and transdisciplinary theories, his collaborative neuroimaging and behavioural psychology experiments have begun to indicate how creative reading-response activities (versioning, text manipulation, image-addition, etc.) – as opposed to the comprehension/critical activities prioritised in schools – enhance the aesthetic experience of poetic language. Meanwhile, the Fellow’s pilot coproduction work with young people – in partnership with app-developers and literacy organisations – is demonstrating how mobile apps can offer young people unprecedented access to poems, opportunities for creative reading-response, and safe ways to engage with peers, fostering creativity, expression, and connection. This project will synthesise these methodologies, collaboration networks, and empirical foundations, leveraging the FLF scheme’s unique scope and support to inaugurate a uniquely large-scale, transdisciplinary, and community-informed investigation of how creative interaction with poetry influences literacy engagement, and incorporate these findings into a tech-based solution capable of supporting literacy at scale and generating new knowledge of literacy practices and their wellbeing benefits. The project’s two workstreams will be fully integrated, shaping and propelling each other: (1) a series of lab-based behavioural and neuroimaging experiments specifying the mechanisms behind creative reading-response’s effects on poetic language processing for young people, and (2) applied mixed-methods-research exploring how creative poetry practices can support literacy engagement and wellbeing, using workshops, interviews and secondary data analysis from literacy organisation partner datasets. The project will be guided throughout by a coproduction team of young people from the target age-group (12–18yo) and supported by parent and poetry-educator advisors, an academic supervisory board, and the FLF’s rich support network. Young people will be empowered to shape research – informing experiment design, selecting stimulus poems, codeveloping tasks – contribute to community poetry workshops, and guide scientific and policy outputs. Central among these will be the development of the interactive poetry mobile app called ‘ReWriter’, which will be founded on the project’s insights whilst fostering further investigation and translating research into public impact. By year 4’s end, we will have coproduced academic/methods scholarship and open-source data and resources, connected with communities through workshops and festival talks, planned education policy initiatives highlighting poetry and creative reading, and codesigned a ‘ReWriter’ app ready for large-scale user-validation. Further funding will support this validation with diverse users, analysis of usage data and user-surveys to investigate literacy’s effects on psychological wellbeing, and work with external partners and university teams to develop strategies for long-term app sustainability, policy initiatives, future research, and international expansion. With open-science, team co-development, and community-guided principles shaping every facet, this one-of-a-kind project will position the Fellow and team as true research leaders at the intersection of literacy, literary theory, creative practice, neuropsychology, and wellbeing, transcending traditional disciplinary boundaries. Focused on this drastically under-researched intersection and founded on the Fellow’s well-piloted methods, collaborations, and insights, this work will catalyse new scientific discovery, inform education policy/practice, and produce a community-guided, research-backed, tech-supported output capable of affecting large-scale, real-world change.

UKRI Gateway to Research · FY 2025 · 2025-12

Researchers at the newly established Institute for Neuroscience and Cardiovascular Research (INCR) at the University of Edinburgh are investigating how complex biological processes across organ systems influence overall health. A key focus is understanding the interplay between brain and cardiovascular health, particularly how age-related changes in one system may impact the other and shape disease susceptibility throughout the lifespan. Functional ultrasound imaging (fUS) is a highly sensitive imaging technique gaining traction within the international research community for its ability to capture brain blood flow dynamics in preclinical models. Using Ultrafast Ultrasound Imaging1, fUS provides high spatial resolution maps of brain blood volumes with 50-fold greater sensitivity than conventional Doppler imaging.  This sensitivity enables detection of small blood volume changes linked to neuronal activity. fUS can be coupled with another emerging technique, Ultrasound Localization Microscopy2 which tracks the path of individual contrast microbubbles enabling spatial resolution of brain vasculature down to microscopic resolutions. Together, these applications enable 3D mapping of task-induced brain activation, resting-state functional connectivity, and brain hemodynamics and vasculature. The Iconeus One fUS system will add transformative mass to the INCR and provide a platform for collaborative projects between INCR researchers. Embedded within our shared preclinical imaging research facilities in the Biological Research Facility at the BioQuarter site, it will complement existing preclinical imaging scanners. The BioQuarter site accommodates over 1200 researchers and the UoE is undertaking large strategic investments on the campus. Our team includes neuroscientists and cardiovascular scientists and research technical professionals working collaboratively to ensure this technology effectively supports transformative and translational research. fUS will facilitate interdisciplinary studies, addressing specific needs, including: Dynamic imaging of blood flow: Crucial for studying conditions like hypertension, heart failure, and vascular diseases, and understanding cerebral blood flow in brain function, development, and neurodegenerative conditions. Repeated measures in the same subjects: Unlike invasive methods, fUS allows non-invasive monitoring over time. Pathophysiological insights: fUS helps understand how cardiovascular diseases affect neurological health, such as the impact of stroke on cognition or blood flow changes during brain development, aiding research on developmental disorders. Therapeutic development: fUS enables the assessment of therapies targeting both cardiovascular and neurological systems, potentially leading to new treatment strategies. While existing methods like high-field MRI, PET, and conventional ultrasound provide valuable anatomical and metabolic data, fUS offers two key advantages. It can capture rapid changes in blood flow during cognitive tasks or experimental interventions in both anaesthetised and awake, behaving animals. Furthermore, fUS enables multi-modal studies by integrating with techniques like EEG, multi-electrode arrays, PET/MRI, optical imaging and optogenetics providing a comprehensive view of brain and cardiovascular interactions. fUS will be a key asset for interdisciplinary research objectives, such as exploring critical biological mechanisms related to development, ageing, and degeneration in the brain and cardiovascular systems. By monitoring real-time functional changes, like cerebral blood flow, it will help investigate ageing and disease progression. Additionally, it will allow researchers to examine how developmental changes influence disease susceptibility later in life. The research will also promote lifelong health by identifying early biomarkers and evaluating therapeutic interventions that aim to improve quality of life. Tanter M, Fink M. (2014) Ultrafast imaging in biomedical ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control. Jan;61(1):102-19. Couture O. et al (2011) Microbubble ultrasound super-localization imaging (MUSLI),2011 IEEE International Ultrasonics Symposium, Orlando, FL, USA, pp.1285-1287.

UKRI Gateway to Research · FY 2025 · 2025-11

Biological immunotherapies have proved an effective way of treating a variety of diseases. Cancer immunotherapies, such as immune checkpoint inhibitors, have offered new and exciting treatment options, rapidly becoming established in clinical practice. However, signalling pathways that contribute to the development of diseases such as cancer are often also used by other cells in the body, making it difficult to treat the diseased cells without causing unwanted side-effects in other cells. Currently available immunotherapies are also not effective in all groups of patients. For these reasons, new and more targeted therapies that are focused on to disease relevant cells are urgently needed. Macrophages are an innate immune cell type found in all organs of the body. Although macrophages usually help to fight infection and maintain healthy organ functions, they have also been shown to play a role in the development of cancers, including those of the digestive tract. In the UK, more than 60,000 people develop cancer affecting their oesophagus, stomach, small intestine or bowel each year, with a 5-year survival rate between 12 and 53%, depending on the affected area. Immunotherapies that target macrophages in these tissues to promote their anti-tumour functions are not yet available but hold exciting potential to expand the repertoire of available therapies for patients which exhibit side-effects in response to untargeted therapies and for patients which don’t respond to conventional immunotherapies that mostly promote anti-tumour functions of adaptive T-cells. We have identified a potential macrophage-specific molecular target, called NRROS, that could be used to develop new therapies for cancers. This molecular target has been shown to regulate macrophages in the brain, but little is currently known about whether it also regulates macrophages in other organs such as the those of the digestive tract. The effects of targeting this molecule to treat cancer are also largely unknown. The aims of this proposal are to study the role of NRROS in regulating the functions of macrophages in tissues of the digestive tract, and to determine whether it could be developed as a new target for the treatment of intestinal cancers. We will achieve our aims by addressing the following three questions: 1) What is the role of NRROS in regulating cancer-relevant signalling pathways in different tissues of the digestive tract and in different types of macrophages? 2) Does NRROS regulate intestinal macrophage functions and inflammatory responses? 3) Does NRROS-deletion improve disease outcome in a model of colon- cancer? We will share our new understanding with other research groups, clinicians, and drug companies interested in cancer drug development, supporting its progress into a new treatment for patients.

UKRI Gateway to Research · FY 2025 · 2025-11

The colonisation of land by plants transformed the Earth; they weathered bedrock, developed the first soils, changed river systems and locked up huge reserves of carbon as biomass. The radiation (spread) of plants is predicted to have caused global cooling, changes in atmospheric CO2 and O2 levels and a mass extinction event. However, linking specific events in plant evolution to these changes, on a causal basis, has proved to be difficult and contentious.  This means that our understanding and estimation of the impacts of plant colonisation on the Earth is still unclear. The primary objective of this work is to address this major unresolved question in the natural sciences. Our lack of understanding of the global impact of plant colonisation results from uncertainty in both how much of the continental surface was covered by plants and how plants physically interacted with the Earth system during their early evolution. This information is largely obscured by the very incomplete nature of the fossil record. Due to the limited fossil record, previous attempts often completely ignore fossils and instead assess the impacts of land plant colonisation based on extrapolations from living species. The obvious limitation here is that this approach overlooks our only direct evidence for early plant life and does not take into account the origin of new functional traits and plant groups during plant evolution. To understand and estimate what impacts plants made on the Earth system we urgently need a new approach. Deep time ecological modelling that directly incorporates data from fossils provides the solution to this problem. We will use this approach, for the first time, in project MapRad. Our proposal is underpinned by the recent development of a new rapid deep time vegetation model (FLORA) which can be coupled with an Earth System Model (SCION) to assess global vegetation-climate-biogeochemical feedbacks in deep time. In MapRad, we will push the frontiers of deep time ecological modelling by building the new PALEOFLORA-SCION model that incorporates data from fossils that lived in the time periods under examination rather than extrapolations from living species. This approach is made possible by recent developments in imaging and 3D reconstruction techniques that allow quantitative extraction of morpho-physiological data from previously intractable fossil groups. Our approach is timely as both the recent advances in modelling and fossil imaging were pioneered separately by our project team and will be combined here for the first time. We have three key objectives: Map the spread of the first forests and their impact on terrestrial biomass Map the pre-forest radiation of land plants from the Ordovician to the Early Devonian Establish the impacts that the evolution of different plant groups made to the Earth system Our project will develop the first evolving model, informed directly by fossil data, that charts the colonisation of land by plants and their rise to ecological dominance. This spatial and temporal map will allow us to test hitherto intractable major evolutionary hypotheses and evaluate the impact that plant colonisation had on atmospheric CO2 and O2 levels, and global cooling and extinction. This major step forward will provide the starting point to extend deep time ecological modelling of terrestrialisation for other groups of eukaryotes, such as fungi and animals, and will allow us to determine how plants created a habitable Earth today.

UKRI Gateway to Research · FY 2025 · 2025-11

In this project we will use a novel approach with 3D printed calcium carbonate ‘mini-reefs’ to visualise how vulnerable cold-water coral habitats will collapse in response to ocean acidification. This will be combined with unique existing evidence by the project team to create the first in silico (computer based) model of cold-water coral reefs, where future habitat loss and timescales of such loss can be quantified. Cold-water corals form large yet fragile ecosystems that support a wide range of biodiversity. Due to their depth and inaccessibility, these important, biodiversity-supporting habitats are hard to study directly, and as such face major challenges in their future protection. This creates a significant challenge in determining their tolerance to environmental change, and efforts to date have largely focussed on the environmental impacts to the live coral. However, of increasing concern is the impact of ocean acidification to the dead coral skeletons that form the foundation of these structurally complex habitats. Ocean acidification leads to the dissolution of dead coral skeletons and crumbling of the 3D reef structures they make through the process of coralporosis. As the dead coral becomes more porous, they become unable to support the weight of the live coral above them, leading to habitat crumbling. As the dead coral skeleton forms the major component of most cold-water coral ecosystems, and is where a significant amount of the biodiversity in these ecosystems is found, its loss fundamentally changes the function of these habitats. The project team has led the research characterising coralporosis and has substantial evidence on this process and timescales based upon experimentation of small coral colonies. To upscale this understanding to reef-scales, the team will create replicable ‘mini-reefs’ using new 3D printing methodology where 3D prints can be made entirely from 100% calcium carbonate. These mini-reefs will be created in a variety of formats to represent the natural variability of cold-water coral habitat structures, and will be based upon our existing database of computed tomography images of coral skeletons. We will subject these mini-reefs to acidification conditions to quantify how much habitable volume is lost (i.e. the spaces within the framework), and how quickly this loss occurs. We will create in silico models that will be validated against this experimental data (which includes structural and mechanical analysis) and existing coralporosis data acquired by the project team in August 2024 (through a Diamond Light Source synchrotron grant to analyse long-term coral experiment samples). These computational models will allow us to quantify how projected climate change scenarios will lead to habitat loss over known timescales. This approach will greatly increase our understanding of what CWC reefs of the future will look like, when these changes may occur on an ecosystem scale, and how quickly that will happen.

UKRI Gateway to Research · FY 2025 · 2025-11

The fire at Grenfell Tower in June 2017, and the subsequent inquiry into how it happened, made clear the threat posed by the weakening and improper enforcement of regulations that protect public safety. The inquiry has identified, among other causes, the contribution of UK government initiatives that sought to cut “red tape” and reduce “burden”. Its final report, published in September 2024, states that “the pressure […] to reduce red tape was so strong that civil servants felt the need to put it at the forefront of every decision”, and concludes that “…it was not in the public interest to allow the policy on deregulation to impede the ability of officials to promote changes to regulations […] that would improve public safety” (Grenfell Inquiry Phase 2 report, volume 1, 150; 160). The deregulatory agenda was not the most prominent part of the inquiry’s work, and the report is unusual in directly linking an initiative like the “red tape challenge” to regulatory failure. But it highlights the importance of understanding where these initiatives come from, how they work, and what implications they have for health, environmental and social protections. The overarching aim of this project is to inform and promote understanding of these regulatory management rules, and how they might better serve societal interest. Rules about when and how regulation is created are commonly referred to as “Better Regulation” policies. They include processes like impact assessment and evaluation, as well as commitments to reducing red tape and simplifying regulation. Heavily institutionalised, they structure the everyday procedures that civil servants follow when developing policy. Better Regulation is a central tool that governments use to ensure that all policy – in every sector – is based on evidence, engages stakeholders, and responds to priorities. These rules are not politically neutral. The project from which this proposal emerges – Better Regulation for Better Health (BRBH) – explored how Better Regulation affects the making of EU health policy. It found that these rules are used by officials to pursue their political objectives, and by corporate actors to lobby for their interests. It demonstrated that processes of measuring, counting, and monetising regulatory costs fail to adequately capture the benefits of health protections, and how narratives of Better Regulation have the potential to ‘chill’ the development of legislation to promote health. Working with civil society organisations (CSOs) in Brussels, the project has built awareness of Better Regulation and a stronger capacity to advocate for change. The Rethinking Red Tape project significantly extends and scales up this work, by moving beyond the health sphere (encompassing environmental and social policies) and developing a specific focus on the UK. The project will unpack the micro-level methodologies that underpin regulatory management, the meso-level instruments that implement it, and the macro-level agendas that it promotes. It asks whether quantification and other methods of assessing policy impact can be adapted to better capture societal costs/benefits, examines how instruments like the “one-in-one-out” approach to regulation work in practice, and explores how the UK’s regulatory management agenda shapes health, social and environmental legislation. By engaging CSOs and governments, and connecting scholars working in different fields, the project seeks to create and support networks of actors who can increase understanding of, and influence how, regulatory management operates.