University of Nottingham

UKRI Gateway to Research · FY 2026 · 2026-09

Our understanding of the physics that governs our Universe in incomplete.  We don’t know the nature of 95% of the material in the Universe today. In order to make sense of the cosmology we observe we need to invoke two new substances; dark matter which clumps together around galaxies, and dark energy which accelerates the expansion of the space in between galaxies. Even the 5% of the material in our Universe which we do understand through the Standard Model of particle physics is missing key pieces of its jigsaw puzzle: how did that matter arise in the early Universe? Why is the universe filled with matter and not anti-matter? Combining the Standard Model with gravity raises more questions still: is there a unifying quantum theory of particle physics and gravity?  How do the laws of physics behave in and around black holes? This proposal brings together a team of internationally leading researchers to answer these questions and more, to make significant advances in our knowledge of fundamental physics. In trying to answer these questions, there are times when we realise that we do not yet have the right computational tools to find the answers, or that, using the methods we have, the calculations we need to perform are just too lengthy to be practicable. One strand of our research seeks to develop new tools to speed up such calculations, and make connections with other systems with analogous physics, in order to provide new insights. When it was young, our Universe went through a number of very rapid transitions, which also require novel approaches to allow us to make precise predictions.  This period of the Universe’s history is particularly exciting to study now because recent observations of gravitational waves allow us to test our understanding of the physics of this period for the first time, probing energy scales well beyond those that can be reached in a particle collider. Observations of gravitational waves have also, in the last decade, revolutionised our ability to understand what happens when gravity is very strong, for example around black holes and neutron stars. This allows us to test whether general relativity is really the right theory of gravity as well as to determine how the particles of the Standard Model, and also those proposed to solve the fundamental questions the Standard Model leaves open, behave in such extreme environments.  Cosmology also offers many opportunities to search for new physics, and explanations of fundamental mysteries, on length and distance scales well beyond what could be reached in any terrestrial experiment. This allows us to determine, for example, whether black holes, formed in the early Universe, could fulfil the Universe’s need for dark matter, or whether dark energy can be explained by theories of quantum gravity. Conversely, we will also develop new opportunities for laboratory experiments to tell us about the nature of the missing components of the universe. This proposal brings together the very large and the very small, the beginnings of the Universe and its behaviour today, physics at very high energies and the physics of strong gravity.  The fundamental questions we seek to address are interconnected, and making progress requires exploring all of these regimes to understand what is possible theoretically and what is allowed by experiment and observation.

UKRI Gateway to Research · FY 2026 · 2026-07

Chronic wounds are a significant burden to patients and healthcare providers worldwide. Globally, wound care expenditure reached a staggering $148.65 billion in 2022 [1]. In 2024 the NHS cost of wound management was £10 billion, with 3.8 million people living with a chronic wound (7% of the adult population) [2], [3]. Healing can take months, and infection in 25% cases diabetic foot ulcers (DFU) leads to limb amputation [4]. They also carry high morbidity and mortality – for example, diabetic foot ulcers (DFUs) have a 5-year mortality rate of around 50%, rivalling or exceeding many cancers [5]. Clearly, intervening early before a wound deteriorates is critical. We have made crucial steps towards solving this problem, through an innovative approach to remote monitoring.  Our recently developed system uses a single inexpensive (<£20) optical fibre array incorporated into a wound dressing to monitor key parameters associated with wound status. This can facilitate earlier intervention by clinicians, thus improving wound care. Our health economic modelling indicates that a 10% reduction in DFU prevalence and complications via preventing amputations, reducing healing time and severity, and substituting care (less community nurse time) could save the NHS as much as £250 million per year. We have recently completed a clinic-based study of 10 patients with DFUs using our system under DPFS project MR/R025266/1. We have successfully measured temperature, humidity, ammonia and carbon dioxide for each subject for 4 visits. We have identified that temperature and ammonia are the two most promising parameters that can be correlated with wound status. While preliminary data confirm the technical potential of our sensing approach, a critical translational gap and go/no-go inflection point in our approach remains: the lack of a scalable, reliable method for sensor fabrication that is reproducible and cost-effective. Currently, we implement an artisan approach in which each sensor is manufactured and calibrated individually, which is impractical for fabricating the sensors required for a larger study. If we can achieve reliable sensor fabrication, it will bridge the gap to a larger scale trial in the community and subsequent widespread deployment. The main aim of the proposed work is to form an interdisciplinary team with expertise in manufacturing and coatings to develop an automated approach for reliable manufacturing of optical fibre ammonia and temperature sensors. To achieve this aim and progress toward a future community trial, it is essential to: 1.    Construct a semi-automated robotic apparatus for coating sensors  2.    Optimise coating conditions for reliable sensor fabrication 3.    Demonstrate manufacture of 200 temperature and ammonia sensors with <5% variability in sensitivity Without these data, we cannot credibly apply for larger translational funding (e.g., DPFS or NIHR i4i Product Development Awards. After we have developed an apparatus to manufacture sensors at scale, the next step is to conduct an appropriately powered community-based study with our clinical team aimed at determining the correlation between ammonia, temperature and wound infection. References  [1] https://doi.org/10.1177/21621918251359554 [2] https://doi.org/10.1111/iwj.14616 [3] https://doi.org/10.4239/wjd.v13.i12.1106 [4] https://wounds-uk.com/wp-content/uploads/2025/03/WUK_21-1_54-57_FLEN_Roadshow-AB-v4.pdf   [5] https://www.healthrecoverysolutions.com/blog/redefining-efficiency-three-benefits-of-virtual-wound-care-consultants

UKRI Gateway to Research · FY 2026 · 2026-06

What did the voices of Britain sound like during and after the Roman period? What can the remains of language convey about the construction and expression of identities and life in early Britain both within the Roman province and beyond the frontier? How did the waters around the island serve to connect or separate communities? In this project we analyse the sociolinguistic complexity of Britain from the century before Roman rule to the three centuries after. We explore voices expressed in writing, interpret symbols and images in stone, and reconstruct underlying cultural contexts and connections. The relative lack of historical sources for Britain and many neighbouring communities in this period makes writing history challenging and dependent on using the material and approaches from multiple disciplines—sociolinguistic, linguistic, epigraphic, historical, art-historical, and archaeological. Integrating these multiple disciplines, appreciating the Irish, Continental, and Scandinavian contexts, and incorporating longer-term post-Roman dialogues can reveal the diverse voices of early Britain. This interdisciplinary approach cuts across provincial and chronological boundaries, and combines evidence usually split between Classics/ancient world and Celtic/medieval studies and between their sub-disciplines. These boundaries continue to be a barrier to assessing the ancient dialogues which cross the end of Roman rule, the frontiers of Empire, and the divide between text and image. During the Roman period, for example, Latin inspired both Ogham script and, arguably, Pictish symbols, and in turn local epigraphies inspired regional variation in Latin inscriptions and monuments. After centuries of isolated study, the integration of these materials will bring deeper understanding of cultural entanglements. We will integrate a range of new later-period datasets with the large datasets generated by the ERC-funded LatinNow project, including Roman Inscriptions of Britain Online (RIB Online), to pursue novel lines of inquiry. A step change comes from testing pre-trained AI models to leverage millions of data points and images across multiple datasets, to recover regional and social patterns. Combining standard analyses with higher-risk AI explorations will add fresh information for the reconstruction of the experiences of life under and after Rome, the nature of local and non-local identities, regional and social patterns, and connectivities. The multidisciplinary Voices team will: ·        produce the first comprehensive sociolinguistic description and analysis of Roman and early post-Roman Britain, revealing linguistic differences across regions, settlement types, social groups, locals/non-locals, and genders; ·        explore the regional, social, and temporal dimensions of the inventions and use of writing systems and expressions in stone, to reveal the sociolinguistic messages of inscriptions, symbols, and images; ·        identify the reasons for the variety revealed, including the underlying cultural entanglements stretching beyond the end of Roman rule, the impact of migration and fixity of communities, the impact of Roman rule, the role of Continental and Insular neighbours, and the Channel, the Irish Sea, and the northern frontier as connectors and dividers. This project will feed into the writing of a broader-based socio-cultural history of early Britain, have ramifications for the understanding of Britain’s cultural heritage, and inform discourses on imperialism, migration, and multiple and mixed identities. Through collaboration on collections and exhibitions with museum partners, the Nottingham University Museum, the Roman Baths Museum, and The British Museum, and teacher training and school curriculum leadership with Classics for All and the Classical Association, we will help shape the national discourse about Roman Britain and its legacy.

UKRI Gateway to Research · FY 2026 · 2026-06

My research examines Yugoslavia’s development strategies from the late 1950s to the early 1970s, focusing on its efforts to integrate into the world market while navigating the constraints of its socialist self-management system. I explore political debates on development strategy within the League of Communists of Yugoslavia in two key contexts. First, I analyse Yugoslavia’s economic relations with Western financial institutions, including its interactions with the International Monetary Fund (IMF) and the World Bank. This involves examining the influence of trade policies, foreign debt, and market internationalization on Yugoslavia’s socialist economic structures. Second, I investigate the impact of geopolitical factors on Yugoslavia’s economic trajectory, particularly its relations with the United States, the European Economic Community (EEC), the Non-Aligned Movement, and the Soviet Union. The Library of Congress collections provide essential primary sources for this research, including: National Security Archives: microfilm collection of the records from National archives pertaining to 1945-1949 and 1950-1954. Oral histories from various US diplomats called Frontline Diplomacy, like Walter Roberts, Cole Blasier and many others. Foreign Relations of the United States (FRUS) records detailing U.S. economic and diplomatic policies toward Yugoslavia between 1945-1970. Congressional hearings and reports on Yugoslavia’s political trajectory and trade policies. World Bank and IMF historical reports. A fellowship at the Library of Congress would allow me to analyse these materials to understand how international economic governance influenced Yugoslavia’s political debates on development strategy, trade integration, and economic policy implementation within the broader context of Cold War economic history and global development policy.

UKRI Gateway to Research · FY 2026 · 2026-04

Is the hybridisation of forced migration and human trafficking a weapon of secret intelligence and sabotage? How far do states use the fear of people on the move as a propaganda vector to divide and subvert western society?    Answering these key questions is the focus of this early-stage proof of concept project. Taking as our starting point the Palermo (trafficking) Protocol constituent elements of act, means and purpose, we will explore an emerging potential scenario wherein vulnerable populations may be recruited (the act), forced (the means) and exploited (the purpose) to provoke internal discord, attack infrastructure, and manipulate public discourse. Examining activity below the threshold of kinetic warfighting – intelligence gathering, covert influence, lawfare - we will show if, and how, secret statecraft, forced migration and human trafficking are intertwined.   Western intelligence agencies are increasingly warning of ‘Telegram spies’, civilians coerced into espionage and sabotage through gig-economy methods. Academics have found evidence of recruitment by deception for scamming farms targeting the West, coercive migration, and human trafficking for armed conflict and in terrorism contexts. Using Maschmeyer’s (2023) theory of subversion – the exploitation of vulnerabilities in an adversary’s society through propaganda, sabotage, and espionage – we propose that trafficking for hybrid activity is an overlooked, yet important, area. We intend to establish if and how this phenomenon is used tactically for intelligence/sabotage and strategically to exploit fears of migrants for propaganda purposes.   Our objectives are to:   1.    Explore the extent to which forced migration and human trafficking serve as instruments of subthreshold secret statecraft (espionage, sabotage, disinformation).   2.    Investigate the operational logic and conditions under which states, such as Russia and North Korea, weaponize human mobility, identifying varying patterns of coercion, recruitment, and manipulation.   3.    Develop an initial typology of hybrid exploitation that informs future interdisciplinary research.    4.    Challenge prevailing understanding of exploitation (not defined in international law) and its characteristics (financial and physical harm), incorporating non-material dimensions such as ideological manipulation, reputational harm, and psychological destabilization.   5.    Assess the role of weaponised migration in the disinformation cycle, tracing if and how real-world events are transformed into propaganda narratives shaping public discourse.   6.    Identify policy frameworks which may require amendment to address and mitigate these phenomena, including protecting its victims.   A novel conceptual design will bridge the fields of intelligence, strategy, and trafficking and ask if, and when, trafficking is recognisable as a tool of secret statecraft. A two-stage taxonomy of exploitation will develop: (1) the tactical use of trafficked individuals for espionage/sabotage, and (2) the strategic deployment of wider migration narratives to provoke societal division. The proof of concept will link disinformation with the instrumentalization of human vulnerability, offering actionable insights for national security, migration governance, and counter-disinformation. We test against a set of provisional hypotheses:   H1: Hybridised migration and human trafficking operate through a dual typology – direct exploitation (espionage/sabotage) and indirect exploitation (propaganda narratives) – with distinct strategic logics and implications.   H2: Hostile intelligence agencies increasingly adopt a gig-economy model of sabotage, leveraging low-tech, low-cost recruitment of victims.   H3: A temporal typology of exploitation exists, with coercive practices occurring before, during, and after migration journeys, each stage serving different goals.   H4: These strategies succeed by blurring civilian and military domains, exploiting humanitarian norms, and amplifying societal divisions, with the project seeking to map and counteract such fearmongering.    

UKRI Gateway to Research · FY 2026 · 2026-03

Coercive control is an urgent and pervasive social problem. It constitutes a pattern of abuse, typically taking non-physical forms, having detrimental and long-lasting impacts on victims. It includes psychological abuse, threats, humiliation, monitoring, isolating one from friends and family, and financial abuse, among others. It exerts forms of control that deeply harm victims, causing loss of confidence and potential emotional, physical, social, cultural and religious distress. It is most prevalent in the domestic sphere and is still not well understood by professional services and publics alike, yet it has been criminalised since 2015. As with other forms of domestic violence, women are disproportionately harmed. Where coercive control is reported, this is most often among white, middle-class women, yet there is every indication that the problem extends well beyond this community. Blackburn is an urban community experiencing high levels of socio-economic deprivation. It is vibrant and diverse but has been overlooked in terms of urban regeneration. Our aim is to investigate coercive control within a disadvantaged and much neglected urban demographic where reporting of coercive control is low: South Asian women. The objectives include  (1) developing a collaborative cultural network between South Asian women, researchers and community practitioner activists (S.A.S Rights), with policymakers (Lancashire’s Police Crime Commissioner, Lancashire Partnership Against Crime, Blackburn with Darwen Borough Council and Blackburn College); (2) deep listening to South Asian women’s accounts of coercive control; (3) culturally expressing those experiences through community theatre; (4) develop policy with participants and policymakers to enhance community cohesion and urban renewal in Blackburn (including new police training resources) on managing coercive control in diverse communities; (5) scaling up the project to policymakers and women beyond Blackburn. Forum theatre enacts a non-hierarchical and participatory approach which addresses social issues impacting on marginalised individuals but, crucially, maximises voice and empowerment with outputs designed by them. In a supportive environment, we will cultivate composite theatre monologues, together with the women, about coercive control, devised from in-depth interviews, but with each monologue drawing on various stories to ensure individuals are not identifiable. This will culminate in a locally-produced theatre performance that will be filmed, for further impact engagement opportunities. This project is a timely one. Coercive control has hitherto been underexplored in relation to religiously diverse and socio-economically challenged urban locations, with such communities experiencing specific complexities given barriers of marginalisation and stigmatisation. This project will learn vital insights, foster empowerment and collaborative learning and education about rights. The project will support the cultivation of local peer experts on coercive control and will generate a film output for further knowledge exchange (with the potential to be upscaled to other locations with successful follow-on funding). This research will consolidate various interest groups and perspectives to develop targeted resources using a sensitive and inclusive approach; moreover, generating crucial new perspectives that draw together arts interventions, religion and gendered violence expertise and policy impact.

UKRI Gateway to Research · FY 2026 · 2026-03

Our brains, like the rest of our bodies, can be affected by age and disease impairing brain health. Poor brain health varies between subjects and may not lead to clinical symptoms, but predicts worse outcomes across diseases. Clinical scientists use the term “brain frailty” in analogy to physical frailty to describe cumulative brain damage that indexes a higher risk of mortality and generally poor outcome from neurological and non-neurological diseases. It reflects changes in brain structure and function that increase the risk of slower thinking, memory problems, and conditions such as dementia or stroke. Research combining brain scans with functional assessments has shown that patterns of shrinkage of certain brain regions, small blood vessel damage, microbleeds and reduced communication between brain areas are all linked to both physical frailty and faster cognitive decline. Importantly, global brain health is increasingly recognised as a marker of treatment-related central neurotoxicity limiting quality of life in cancer survivors. Our multi-professional, multi-disciplinary team has a strong track record in data-driven translational brain research that includes as outcomes a series of analytics pipelines that process brain image and related data to obtain markers of brain health that can track frailty and interrelated disease progression and outcomes. To study brain health and frailty effectively before it can be exploited for personalised clinical decision making, we need access to large and diverse populations containing information that include, for example, brain MRI scans, clinical records, genetic data, demographics and lifestyle factors. Because this data is sensitive, it cannot be easily accessed or simply shared and moved across hospitals and research teams. Instead, researchers use Trusted Research Environments (TREs), which are secure digital spaces that allow approved experts to analyse data safely without moving it. The DARE-UK TREvolution programme is developing new ways to connect these secure systems so that analyses can be run across multiple TREs at once. This approach, known as federated analysis, enables collaboration at national and international scale while increasing research power, maintaining privacy and strong data-governance standards. The Brain fRAilty Integrated through Data federation (BRAID) project will bring together a team from the University of Nottingham, Nottingham University Hospitals NHS Trust as a TRE node, The SAIL databank from the University of Swansea, The University of West England and the Dementias Platform UK (DPUK) TRE to test how well the existing TRE federated infrastructure supports our analytical approaches for data-centric brain research, having brain frailty as our case study. Using advanced analytics and machine-learning methods to synthetic data derived from DPUK datasets, we will identify early signs—or biomarkers—of brain frailty and examine performance, how efficiently federated TREs process complex brain data, and how securely they manage and share results. This will help identify where improvements are needed to make the TREvolution technologies more reliable, scalable, responsible and user-friendly. Alongside the technical work, we will involve members of the public throughout the project. By running workshops and other engagement activities, we will explore and document people’s views on privacy, data use, and the role of the new technologies from TREvolution and federated brain frailty data analysis in health research. Their feedback will help us shape the design and communication of our methods and ensure that the development of the DARE-UK technologies also reflect public values, addresses concerns and meets their expectations.

UKRI Gateway to Research · FY 2026 · 2026-02

We are developing a novel 3D-printed bone graft substitute for restorative dentistry. It exploits the ability of cells in our body to feel and respond to the shape of their environment, interpreting it as instructions for how to behave, accelerating new, stable bone formation. By using cutting-edge additive manufacturing (AM) technologies capable of producing these shapes with exceptional precision, this research represents a new approach to healthcare material design for treating bone injuries using regenerative medicine. Bone is the second most transplanted tissue after blood, with over two million procedures performed globally each year. With changing demographics and an increase in population, this number is increasing, driving the need for improved synthetic substitutes as alternatives to autografts and allografts. Whilst our technology has the potential to be applied to a range of orthopaedic indications, we have decided to initially focus on dentistry based on feedback from clinicians on the clinical and market need. This market is also relatively low volume per treatment and would allow us to develop our manufacturing and quality control processes before expanding into other clinical areas. Bone grafting is a common procedure in dentistry, especially when there is insufficient natural bone to support an implant. Typically, synthetic or animal-derived substitutes are used due to practical barriers to using auto/allograft in a dental setting. It is essential that primary stability is achieved in the grafted area before inserting the implant, a period which often lasts for up to a year as the new bone slowly forms. This extended period with missing teeth causes patients both physical discomfort due to difficulties with chewing and speech, as well as emotional distress through increased self-consciousness and reduced self-esteem. Moreover, despite the extended wait period, up to 70% of dental implant failures occur in grafted regions due to low-density or poor-quality bone, leading to revisions and further suffering. This is a result of current synthetic bone grafts often lacking the biological cues needed to actively guide cell behaviour, resulting in poor integration and slow healing, contributing to the higher risk of implant failure and confirming the need for improved alternatives. We have already demonstrated that a particular design we discovered, DesignX, actively and innately promotes cell and tissue infiltration and supports bone-like tissue deposition in the laboratory. In a subcutaneous implant model, we have demonstrated that this is conserved, promoting tissue integration and vascularisation. Using the latest 3D printing technologies, we can fabricate this new type of material within commercially viable timeframes. We now face a single, critical, high-risk aim: demonstrating that when implanted into a real bone defect, these materials are effective at supporting bone formation. Our project objectives are to assess this by implanting our new synthetic graft material into a real bone defect and quantifying new bone formation through 3D Imaging (microCT scanning) and histology. Only by bridging this gap in this proposal will we be provided with the data needed to attract the funding and industry partners needed to translate this product to clinical use.

UKRI Gateway to Research · FY 2026 · 2026-02

Speculative online trading platforms have rapidly grown in popularity and transformed the financial digital landscape. These apps give ordinary people access to complex risky financial products, including cryptocurrencies and contracts-for-difference (CFDs). Marketed as investment opportunities, CFD adverts must show a disclaimer that up to 89% of their customers lose money – odds that make the roulette look attractive. Cryptocurrency values move more with social media endorsements than economic indicators. These speculative trading platforms appeal disproportionately to gamblers, and yet are not subject to gambling regulation, such as deposit limits or self-exclusion schemes. This fellowship will transform our understanding of the links between speculative trading and gambling, providing data-driven evidence to inform policy changes. While gambling is recognised as a public health issue, and associated with a number of harms (financial, health, social), speculative trading remains regulated as investments. Policymakers have tightened digital gambling regulation, but the UK government’s 2023 Gambling White Paper overlooked speculative trading entirely. This regulatory blind spot risks exposing financially vulnerable people to gambling-like harms under the promise of large gains. It also risks creating a loophole whereby those restricted from gambling by tighter regulatory controls might migrate into trading. The project will use a unique new dataset being collected by the Smart Data Donation Service (SDDS). Unlike previous studies that rely on self-reports, SDDS combines real-world app usage histories, YouTube viewing data, and survey responses. This enables unprecedented analysis of actual behaviours. The project has two main objectives: 1. Establish the overlap between speculative trading and gambling, investigating whether the same individuals who use speculative trading apps also use gambling apps. 2. Understand how social media (YouTube trading “educational” videos) influences consumer engagement with speculative trading apps. Promoted as educational or aspirational, such videos may encourage and normalise risky trading activities. I will also test whether demographic and individual differences associated with gambling harm (impulsivity, age, sex, income level, loneliness) predict speculative trading engagement and social media influence. I will use these insights to help policymakers understand which groups are most vulnerable, and how they relate to gambling harm. Experts-by-Lived-Experience (people harmed by speculative trading) will be consulted to ensure analyses focus on the most relevant apps, media, and behaviours, helping create impactful outputs. With the insights of this fellowship, I will write policy briefs, engage with government, regulators and media, and create a professionally-developed educational video that highlights the risks of speculative trading and social media influence. This fellowship is designed for maximum academic and societal impact, aligned with the Smart Data Research pillars of Digital Society and Health and Wellbeing. It will advance digital finance and gambling research by using robust, large-scale behavioural data. It will generate evidence to support better consumer protection through new policy and regulation, such as extending self-exclusion tools and affordability checks to trading. It will contribute to public health campaigns, raise awareness of risks, help the design of targeted interventions, and contribute towards reducing stigma by showing how speculative trading operates much like gambling. For myself, it will provide training in large-scale data analysis and policy engagement, strengthening my leadership and reputation in speculative trading research. In short, this fellowship will deliver the first data-driven evidence of links between speculative trading, gambling, and digital media influence, designed to change our understanding, perception, and regulation of this harmful activity.

UKRI Gateway to Research · FY 2026 · 2026-01

Questions concerning ethical aspects of AI continue to be dominant in academic discourses as well as national policy, professional, and organisation discussions. The conceptualisation of AI as socio-technical ecosystems is widely used but its implications for questions of ethics and responsibility are not well understood. The ROSALIE project will make a crucial contribution to discussions of ethics and responsibility in AI by providing a conceptually sound and empirically rich analysis of how responsibility is perceived, attributed and enacted across different AI ecosystems. A comparative study exploring the differences and similarities between German and UK AI ecosystems will be undertaken to identify defining features of such ecosystems that influence responsibility. The comparative methodology will be informed by a conceptual analysis of normative positions in AI ethics. This will be complemented by a stakeholder analysis and a detailed study of research and funding conditions (30 Expert interviews, 15 each country; 3 Stakeholder Focus Groups with participants of both countries). The project will undertake 10 in-depth case studies on organizations (5 UK and 5 Germany) (document analysis and 3-5 expert interviews each case). The overall comparative analysis of the UK and German AI ecosystems and their constituent components (also 2 Workshops with respectively 3-5 experts from each country) will provide answers to our research questions of how AI ecosystems emerge in relation to specific cultural-institutional boundary conditions and how ethical and responsibility questions are  identified, interpreted and addressed in such ecosystems.  

UKRI Gateway to Research · FY 2026 · 2026-01

The measurement of ultrafast phenomena such as phonon, electronic, and optical dynamics allows us to probe nature at largely unexplored time and length scales. Technologies that can access these regimes, e.g. time-resolved pump-probe spectroscopy, improve understanding of our universe and its underlying physics, but have not yet been exploited for addressing real-world challenges particularly in clinical healthcare. A range of biological processes play out on ultrashort and ultrafast scales, for example: changes in fluorescence lifetime on the nanosecond scale due to changes in cell chemistry, or the mechanical straining of subcellular structures due to the presence of nanosecond period acoustic waves. Techniques that are sensitive to the latter reveal mechanical material properties of biological cells and tissue, and these play a crucial role in the progression of a range of cancers as they progress from single cells to complex metastatic tumours (often characterised as “stiff”). Minimally invasively characterising disease at the single-cellular scale is a major global challenge, that if solved would enable clinicians to fundamentally understand and diagnose disease at its earliest stages. Current state-of-the-art technologies for studying mechanical properties of microscopic systems are expensive, low resolution (elastography), and/or cumbersome requiring large clinically-incompatible infrastructure (atomic force microscopy). Optical pump-probe technologies, such as Brillouin spectroscopy, also access these material properties yet have a key differentiator: they are endoscopically viable for future in-body diagnostics. However, similarly, these technologies are currently prohibitively expensive (~£500k), cumbersome (10m2), and slow (seconds per measurement). In this New Investigator Award, I will engineer an optical pump-probe technology that is cheaper (£50k), portable (fits on a trolley), endoscopically deployable, and fast (hundreds to thousands of measurements per second). Typical pump-probe systems require multiple metre-long laser cavities and take seconds to record signals due to long laser synchronisation and signal averaging times. To improve these by several orders of magnitude, my time-stretched phononic spectroscopy technology will leverage several engineering breakthroughs that up until recently have not been possible: Miniature (pocketbook-sized) ultrafast fibre lasers. A new optical sensing paradigm, “time-stretching”, which trades extremely fast temporal information for modest changes in the light’s spectrum. Highly dispersive optical systems (e.g. fibre optic-based) that stretch light in time and colour. High dynamic range sensor arrays for astronomy and NIR spectroscopy that detect faint changes in light intensity from large background signals. Advancements in fibre optic imaging probes that enable needle- or endoscope-based microscopy. I will marry these technologies to engineer a new endoscopically viable pump-probe device that brings microscopic tissue-mechanical information to clinicians for the first time while remaining practical, cheap, small, and fast. Time-stretched phononic spectroscopy will redefine state-of-the-art for pump-probe spectroscopy and therefore will find applications in the study of electronic and thermal physics. However, this breakthrough will finally unlock applications of ultrafast pump-probe spectroscopy to the clinical and life sciences. For instance, we will investigate the ultrafast responses of single- and multi-cellular tissue in cancer biology, whole organism analytics, and plant sciences.

UKRI Gateway to Research · FY 2026 · 2026-01

Rice is often termed the world’s most ‘essential’ crop because unlike wheat or maize it is largely eaten directly by people rather than used as animal feed or fuel.  It is an important source of calories and protein for around half the world’s population. Rice is grown across a range of environments from flooded and water-inundated lowlands to harsh upland soils and is vulnerable to the negative effects of climate change in these regions. This means it carries particular importance for global food security and poverty. Rice remains an international concern. While the UK does not grow rice for commercial gain, we increasingly import and consume rice with the associated UK industry worth nearly £1 billion annually. We also deliver an impressive amount of rice research with influence across important areas including fundamental science, genetics, nutrition, and social science. Rice research provides additional benefits as it is an excellent model for understanding all cereal crops. However, the rice research base in the UK requires proper coordination. It is currently not operating to full potential and is capable of greater global reach. This project will build a network of scientists and social scientists to address the limitations to UK rice research and help our research community to meet opportunities and challenges head on. We will create a sustainable network for synergistic collaboration providing global visibility, accessibility and reach. Together we will build routes to ease bottlenecks that slow down research and train the next generation of leaders. By encouraging national and international collaboration, we will help to set the agenda for future rice science and rice production. Through a series of workshops in which will include key global players from Africa, Asia, Europe, the Americas and other regions, the network will help to decide the actions needed to future proof the UK rice research landscape, strengthening and building our contributions to international research programmes, which impact the UK and global economy. Throughout our project we will address urgent issues of equality, diversity and the ethics of operating equitable and fair international collaborations. The ‘OryzaNet’ core team has extensive rice research experience and strong global connections. The network will provide a programme of bespoke, collaborative workshops, meetings, training, mentoring, and enabling the Early Career Researchers (ECRs) who will form the future leaders. We will encourage communication and give all rice researchers a voice in identifying problems and opportunities among the UK research environment and beyond. We will establish interactions with key overseas research groups and stakeholders within dedicated meetings and satellite workshops. Backed by experience from global institutes we will also offer training in strategic and missing techniques to help future-proof the community. These include genomics, phenomics and rice cultivation methods.  We will set up a pilot funding scheme to engage ECR talent that will capture and nurture the ideas of our brightest researchers and help to build their future careers. This will sustainably benefit the UK research community through new global collaborative ventures, innovation in tools, methods and discovery.

UKRI Gateway to Research · FY 2026 · 2026-01

Heterogeneous photocatalysis holds the promise of revolutionising chemical manufacturing by enabling cleaner, light-driven catalytic reactions. Unlike traditional thermal processes, photocatalysts can trigger reactions under room temperature and atmospheric conditions as well as using less harmful reagents, thereby increasing safety, and reducing environmental impact and energy consumption. However, achieving precise control over the activity, selectivity, and stability of heterogeneous photocatalysts remains a significant barrier to developing efficient and sustainable technologies. A key challenge lies in applying advanced characterization tools to gain a deep understanding of the dynamic interplay between reactants, solvents, catalysts, and products during these reactions. Traditionally, such tools have been used in isolation, often only assessing the catalyst before and after the reaction due to their incompatibility with the reaction environment. This approach provides limited mechanistic insight, leading to a trial-and-error method in photocatalyst design. This collaboration aims to overcome these challenges by enabling monitoring of catalyst sites under reaction conditions, thereby enhancing catalyst design. By leveraging the atomic-resolution spectroscopic capabilities at the SuperSTEM EPSRC National Research Facility for Advanced Electron Microscopy and the York-JEOL Nanocentre, we will gain unprecedented insights into the mechanisms of light-induced reactions and the conditions under which photocatalysts are activated or deactivated. These advanced techniques will allow us to precisely determine atomic positions, bonding environments, and their implications for photocatalytic activity. The unique capabilities of the SuperSTEM facility, particularly its ability to combine spectroscopy with atomic-resolution imaging, will allow for comprehensive and reliable characterisation of photocatalyst surfaces, shedding light on potential activation and deactivation mechanisms. The environmental STEM at the York-JEOL Nanocentre will enable us to observe surface chemical reactions under near-realistic conditions, offering insights closer to actual reaction conditions than ever before. Focusing on industrially relevant transformations involving olefins, we aim to uncover fundamental aspects of photocatalyst surface chemistry as it adapts to varying reaction environments. This will enable us to correlate these chemical changes with photocatalytic efficiency, leading to improved catalyst designs. This project represents a pivotal collaboration with one of the world’s leading research facilities, positioning my research at the forefront of photocatalysis. It marks a significant departure from traditional approaches to heterogeneous photocatalyst design, advancing the state-of-the-art in this field and distinguishing my work from current trends.

UKRI Gateway to Research · FY 2026 · 2026-01

Rice agriculture is the most extensive use of land for global food production, predominantly for direct human consumption. It impacts the global economy, not only in areas of primary production/consumption. The UK has a thriving rice research community interconnected to institutes in rice growing countries. UK research in fundamental discovery science has enabled complementarity and synergism, feeding into global partnerships and the increased use of rice as a UK model crop. Rice is the primary source of calories and nutrition for >3.5bn people (67% of total global cereal consumption; 23% of protein intake). Population growth predicts rice yield needs to increase by 50% before 2050; this challenge is compounded by environmental change, particularly temperature increases and water shortages. Estimates are that global rice yield declines by 7-8% per 1°C increase above optimum growth temperatures. Rice reproduction, especially pollen development, and photosynthesis, are particularly sensitive to heat stress. It is not known whether the failure of reproduction and therefore seed set and yield is because pollen development is particularly sensitive to heat, or whether it is a secondary consequence of disruption of energy generation by impaired photosynthesis under heat stress, or more likely a combination of both. However, addressing this fundamental question is important to enable effective systems for heat stress resilience to be identified and to understand how they function and thus generate materials that can withstand heat stress in an agricultural field environment. This programme will address this question alongside generating rice germplasm and markers to enable rapid trait deployment in breeding programmes. The work involves a partnership with the International Rice Research Institute (IRRI) in the Philippines, which will enable testing of rice germplasm under in-field conditions of heat stress, and utilisation of their rice populations that have been established to enable screening for heat resistance and thus generation of a pipeline for trait identification and deployment.  It will also involve detailed analysis of several candidate genes that we have identified as promising for delivering resilience to heat stress. The outcomes of this work will be better understanding of the process of heat resilience and confirmation of traits that offer heat resistance in field scenarios. This will generate materials for breeding using elite germplasm which will be assessed at IRRI and form part of their future breeding programmes. The outcomes of this research will also be directly transferable to other cereals, particularly wheat and barley, which also have similar susceptibility to heat stress.

UKRI Gateway to Research · FY 2025 · 2025-12

This rapid evidence review will address the intergenerational transmission of gambling harms, focusing on how parental or household gambling affects children and young people, and on interventions designed to reduce or prevent these harms. Gambling harms are increasingly recognised as a public health issue that extend beyond the individual who gambles to families, communities, and society at large. Children are particularly vulnerable, with potential consequences including poorer mental health, behavioural difficulties, reduced educational attainment, family conflict, and financial insecurity. Understanding these impacts, and the mechanisms through which they arise, is critical for informing effective policy and practice responses. Evidence on how gambling harms are transmitted within families can help shape targeted prevention strategies, improve safeguarding and support services, and guide the design of interventions that reduce risks and build resilience among children and young people. Beyond children, a broader evidence base exists on “affected others” such as partners and families. Reviews have documented financial strain, relationship conflict, and psychological distress. This was also evidence in an evaluation of a gambling prevention campaign throughout Yorkshire, UK (work carried out by the research team; data not yet published). However, there are some key gaps in the current evidence base. Firstly, there is limited synthesis of protective factors and coping strategies that may buffer harm, and very little consolidated evidence on interventions designed to support affected others, such as family-based therapy, financial counselling, or peer support. In addition, existing reviews rarely explore subgroup differences, for example how gambling harms may be experienced differently across socioeconomic groups, cultural backgrounds, or by gender. Finally, evidence is also scarce on the long-term and intergenerational trajectories of harm. By this we mean the ways in which gambling-related harms are transmitted across generations, for example, how children of parents who gamble harmfully may experience ongoing disadvantage in education, health, or financial security, and whether these experiences increase their own risk of gambling or related harms in adulthood. Our review will therefore synthesise the  available longitudinal and life-course studies to explore how gambling harms accumulate and persist over time. This review is directly relevant to UK policy priorities, including the government’s ambition to reduce gambling harms and protect children. It will provide an up-to-date, comprehensive evidence base to inform safeguarding, service provision, and regulatory decision-making.  

UKRI Gateway to Research · FY 2025 · 2025-12

In this project, we propose a cross-disciplinary research programme aimed at addressing the critical unmet needs of pancreatic ductal adenocarcinoma (PDAC). These cancers have a five-year survival rate of just 3%, despite many attempts to combine existing therapies to improve outcomes. We believe an entirely new approach is needed, and have brought together a diverse team of researchers at multiple career stages and across the disciplines of synthetic biology, materials chemistry, cancer biology, advanced engineering and clinical medicine to address this problem. Context of the research: Pancreatic cancer has a complex and heterogeneous tumour microenvironment (TME) rendering it unresponsive to most conventional therapies. The TME is composed of multiple interacting biomolecules which form a dense matrix, and in addition to cancer cells there are immune cells including tumour associated macrophages (TAMs), natural killer (NK) and CD8+ T-cells  which play a significant role in regulating tumour growth and resistance to treatment. Current treatments largely fail to consider the dynamic nature of the TME, leading to poor patient outcomes. Challenge the Project Addresses The primary challenge addressed by this cross-disciplinary project is the need for more effective and targeted therapies for PDAC. Traditional treatments focus on eliminating cancer cells, but this approach often fails due to the protective role of the TME. The project aims to reprogram the stroma (the supportive tissue surrounding the tumour) rather than directly targeting the cancer cells, thereby overcoming the limitations of current therapies.    Aims and Objectives:  The main aim of the project is to develop a new concept in cancer therapy that uses engineered bacteria to reprogram the tumour stroma. The specific objectives are:  1. Engineering bacteria to produce compounds that release immunomodulators, such as TRAIL and IL-15SA , which can reprogram macrophages and recruit NK cells and reduce resistance to therapies.  2. Deploy responsive polymers that can be co-injected with bacteria and which gel in situ, retaining the bacteria at the peri-tumoural injection site, and which can release bacterial activators on-demand when activated by ultrasound, allowing precise control over the timing and location of treatment.  3. Validating the efficacy of this approach using 3D culture models of PDAC to demonstrate the potential for clinical application.    Potential Applications and Benefits:  This project has the potential to revolutionize the treatment of PDAC and other solid tumours by offering a more targeted and effective therapy. By reprogramming the tumour stroma, this approach could improve patient outcomes and reduce the side effects associated with conventional treatments. Additionally, the use of ultrasound for on-demand activation of the therapy provides a non-invasive and precise method for controlling treatment, making it more adaptable to individual patient needs. The interdisciplinary nature of the project also paves the way for future collaborations and innovations in cancer therapy, with the potential to extend this approach to other types of cancer and diseases with complex microenvironments. The work has been inspired by MRC and Cambridge Pancreatic Cancer Centre workshops with clinicians and patient representatives, and has been co-created by researchers across different disciplines and career stages to address a critical unmet need.

UKRI Gateway to Research · FY 2025 · 2025-12

Anxiety disorders are the most common psychiatric diseases and have become even more common since the Covid-19 pandemic began. These disorders are characterised by excessive fear and avoidance, heightened body arousal, and abnormal brain function in processing and responding to threat. Although treatments are available, medicines can be ineffective and have unwanted side effects, while psychological therapies can have limited or temporary effects that lead to relapse. Anxiety disorders are an enormous social and economic burden that require new treatment approaches. To do this we need to better understand how the healthy brain controls the appropriate expression of threat-related behaviours and arousal states. Academic and industry researchers study the brain basis of threat learning and defensive behaviours in rodents to gain insight into anxiety disorders and potential treatment targets. This research is clinically relevant because rodent defensive behaviours map on well to fear and avoidance, while the brain networks involved are similar in humans. Threat learning is also studied in the same way in rodents and humans, where a harmless cue becomes threatening through its association with an aversive stimulus to cause fear and avoidance. Repeated cue exposure results in extinction, which is new learning that can reduce fear and avoidance. Extinction has important clinical relevance as the basis of exposure therapies for treating anxiety disorders. However, fear and avoidance can persist or return after therapy, highlighting the need for further research on the brain networks controlling extinction. Lagging behind is our understanding of the relationship between different anxiety-related behaviours and arousal states, how extinction affects this arousal, and the brain networks involved. Human studies support measuring heart rate variability (HRV), the natural variation in timing between successive heart beats, as a marker of arousal. This has clinical relevance since HRV is decreased in anxiety disorders and extinction of fear is associated with increased HRV. Human studies also show overlap in the brain networks involved in HRV and extinction. Rodent studies combining brain manipulations with HRV and behavioural measures to investigate the brain networks controlling arousal during extinction of fear and avoidance have huge potential for understanding disturbed behaviour-body interactions in anxiety disorders. We aim to determine the brain basis of HRV during extinction of learned fear and avoidance in rats to improve the clinical relevance of rodent studies on threat learning and defensive behaviours. In Objective 1 we will characterise HRV during fear, avoidance, and their extinction. We will also validate a new non-invasive method for measuring HRV during behavioural testing. In Objectives 2-3 we will use cutting-edge methods to turn on or off a relevant brain area (Objective 2) or brain circuit (Objective 3) to determine how they control HRV during extinction of fear and avoidance. We will also map the different cell types and connections involved in this brain circuit (Objective 3). Understanding how the healthy brain controls arousal associated with extinction of fear and avoidance will lead to new insights on behavioural and bodily disturbances in anxiety disorders, along with their responses to psychological treatment. Mapping the cell types in the brain networks involved will also identify promising treatment targets for future drug development. This is highly relevant to various BBSRC priorities (Integrated understanding of health, Understanding the rules of life, Bioscience discovery) and the UK government’s life sciences vision (Mental health challenges and missions).

UKRI Gateway to Research · FY 2025 · 2025-12

Zimbabwean smallholders live with the aftermath of colonial expropriation which displaced communities onto poor soils with inadequate rainfall and disrupted indigenous knowledge systems (IKS). A colonial agroecological survey (AES), mapped Natural Regions (NR) with reference to requirements for commercial maize and tobacco production. The NR are still used for research, extension (advice) and policy, although it is unlikely that they represent constraints on African farming systems.  To deliver context-sensitive and equitable solutions, science must be part of an interdisciplinary effort in partnership with rural communities, bringing IKS into dialogue with scientific knowledge and critically re-evaluating information inherited from the colonial period. We shall pilot an integrated assessment of Zimbabwe’s NR, including the co-evaluation with communities of IKS and scientific understanding to inform revision of national-scale information. Objectives and interdisciplinary approach. 1.    To re-evaluate NR critically from integrated scientific, historical, cultural and social perspectives Through interdisciplinary reading of internal and archival evidence, grounded in historical methodology but including cultural-linguistic, social and natural science perspectives, we shall examine the methodology of the AES, and its political, economic and social context, to show how this constrained its output.  We shall develop and apply crop models, parameterized with historical weather, soil and crop yield data, to assess how far use of a particular commercial reference cropping system skewed the NR from regionalizations more relevant to African farming.  By recalibrating the model with modern crop and weather data, we shall propose alternative regionalized Crop Production Domains (CPD). 2.    To understand IKS in contrasting environments, and how they can inform practice when related, but not reduced, to scientific information. In participatory research, with four communities in two contrasting NR, we shall co-produce accounts of IKS for local soils and cropping, using mixed methods to combine oral history, social and linguistic investigation of “talk about soil”.  We shall construct local scientific soil information (SSI), by sampling and statistical modelling, then develop a double description to show how IKS and SSI sit in some degree of partial correspondence, and how both can support advice and practice. 3.    To integrate national and local scale findings for impact. Variation of the local IKS and SSI within and between the NR will be compared with the original account of their potential as a first picture of how far the NR ignored the potential of African farming systems, and how far they captured constraints.  The model-based CPD will be compared similarly.  We co-produced this proposal with three partner organizations in Zimbabwe for critical feedback and for pathways to impact. Information about the NR, and alternative CPD classifications to support other crops and systems, and emerging accounts of IKS and SSI, will be shared and discussed with Zimbabwe’s Department of Research and Specialist Services (DR&SS) to explore how it should inform research at their stations around the country, and its interpretation to support extension. We have also agreed to collaborate with the Zimbabwe National Geospatial and Space Agency (ZINGSA) to develop new products on CPD and soil conditions to add to the digital spatial information products it generates to support agriculture via phone apps.   The Integral Kumusha Foundation promotes community development through harnessing indigenous knowledge.  They will provide critical feedback  during the project, and will jointly run a “Communiversity” event in their outreach programme to share findings with their participating communities and stakeholders.

UKRI Gateway to Research · FY 2025 · 2025-12

Carbon-negative innovations are urgently needed to improve the sustainability of global waste management systems. This project will provide the scientific basis needed to scale-up carbon-negative smouldering, a new carbon-negative waste treatment technology that integrates smouldering combustion with carbon sequestration via thermal activation of ultramafic rock. This integration will directly harness energy from waste to drive carbon sequestration. Current waste management systems release 0.1 to 2 kg CO2-equivalent per kg waste. In contrast, our proof-of-concept research suggests that carbon-negative smouldering may sequester up to 7 kg CO2 per kg waste. Given the novel state of this technology, key knowledge gaps related to geochemistry, heat and mass transfer dynamics, and economic and sustainability success factors must be addressed to advance from proof-of-concept to large-scale operation. Tarek Rashwan, Phil Renforth, Christine Switzer, José Torero, and Katherine Dobson will address these knowledge gaps alongside an international team of industry partners. Carbon-intensive waste management is a major societal challenge. Globally, over 2 billion tonnes of municipal solid waste are generated annually, and traditional waste management systems currently output ~5% of global CO2 emissions. These emissions are tough to abate. By 2050, global waste generation is projected to increase to 3.4 billion tonnes per year and will require management systems that output 2.6 GT CO2-equivalent annually. In the UK, major national commitments recognise waste management challenges and aim to maximise resource circularity and minimise environmental pollution, while also pursuing low-carbon solutions needed to reach net zero targets by 2050. Carbon-negative smouldering can improve waste treatment systems, addressing global waste management challenges and contributing positively to the UK’s environmental goals and net zero agenda. Applied smouldering has recently emerged as a scalable, energy-efficient, and sustainable thermal technology. It has been applied to treat hazardous materials and recover energy and resources from challenging wastes, e.g., faeces within off-grid systems in low-income regions and hazardous waste liquids in remote locations worldwide. Smouldering is therefore highly compatible with a circular economy. However, as waste is combusted to CO2, carbon emissions remain a key sustainability limitation. Carbon mineralisation in ultramafic rocks has the potential to sequester 1-10 GT CO2 annually. However, this mineralisation is often limited to 3-10% of total CO2 mineralisation potential due to inhibiting compounds. Thermal activation prior to carbon mineralisation can release these compounds and address this limitation. Carbon-negative smouldering systems can harness energy from wastes to thermally activate ultramafic rocks. Through combining expertise in smouldering, geosciences, and carbon solutions, this project will use experimental and modelling tools to advance carbon-negative smouldering beyond proof-of-concept towards large-scale operation. This project will: Evaluate thermal activation experimentally across smouldering and ultramafic rock conditions, which is needed to quantify the potential for carbon-negative waste treatment. Integrate thermal activation geochemistry processes into an existing smouldering numerical model, which is needed to forecast dynamics in large-scale systems. Identify economic and sustainability factors that govern carbon-negative smouldering scale-up success through a techno-economic analysis and life cycle assessment. Altogether, this project is poised to unlock follow-on opportunities on an accelerated path to carbon-negative smouldering application, including scale-up experiments and field demonstrations. Alongside an international team of partners, our project will open a new field that aims to improve waste sustainability worldwide.

UKRI Gateway to Research · FY 2025 · 2025-12

Context Across history, plant propagation has been essential for both medicinal and food production practices. The UK boasts a rich tradition of plant cultivation dating back to medieval times, where gardens served as vital sources for medicinal herbs. However, much of the knowledge surrounding historical plant propagation techniques has been lost over time. As we face pressing challenges related to biodiversity loss, sustainability and the urgent need to meet net-zero carbon targets, uncovering and understanding these historical practices could provide innovative solutions for modern plant production demands. Challenge Addressed Despite significant advancements in plant propagation techniques, many species remain difficult or impossible to propagate. Simultaneously peat-free solutions for propagation are proving challenging. We address these challenges by studying historical documents which may have preserved alternative options to modern techniques. Many of these texts are not in digital form, requiring manual searches made harder by the evolving language, spelling and botanical terms. By adapting artificial intelligence (AI) tools in collaboration with computer scientists, English language experts, and plant scientists, our interdisciplinary project seeks to rediscover and apply hidden knowledge to improve propagation techniques. Aims and Objectives Our primary aim is to integrate forgotten knowledge of plant propagation from historical texts held at the Royal Horticultural Society (RHS) and manuscript repositories into modern science to improve plant production techniques. Along with identification and validation of propagation techniques and peat-free alternatives and development of new AI search tools, we will observe changes in horticulture influenced by advancements in scientific understanding and look for points of resistance in cultural adoption. Potential applications and benefits: This research will have implications for both academic and practical fields. For example, it will provide new insights into historical plant propagation techniques and peat-free media, identifying new techniques to propagate rare or previously difficult to propagate species, supporting global biodiversity and conservation efforts, and helping meet net-zero carbon targets. Additionally, the AI tools and glossaries we develop will have broader applications in research areas, such as tracing plant species and disease movement over time. Finally we will inform strategies to overcome policy and practice implementation in modern society by studying how points of resistance were overcome in the past. Our project not only aims to advance the field of plant propagation but also to enrich our understanding of societal relationships with plants. The interdisciplinary nature of our work, combining modern science, historical research, and computer scientists ensures we approach this challenge from multiple perspectives and deliver meaningful outcomes for both science and society.

UKRI Gateway to Research · FY 2025 · 2025-12

Context Glioblastoma is the most common and aggressive brain cancer in adults. Despite decades of research even the best treatments currently available provide limited benefits to patients with this disease. New treatments that help the body’s immune system fight cancer (‘immunotherapy’) have worked well in other cancers, but unfortunately not in glioblastoma. It is thought that a key reason for glioblastoma’s resistance to immunotherapy is that the tumour generates an environment that suppresses cytotoxic (cancer-killing) immune responses. This prevents immune cells from attacking cancer cells, making immunotherapy ineffective. Research suggests two immune cell types, myeloid-derived suppressor cells (MDSC) and tumour-associated macrophages (TAM), are recruited by glioblastoma to suppress anti-cancer immunity. Understanding how this is controlled should allow us to devise new treatments. The tumour environment is surrounded by a complex molecular scaffold called the extracellular matrix (ECM), which is a major component of glioblastoma [1]. ECM influences immunity, interfering with normal immune responses and promoting resistance to treatment [2]. My project investigates the relationship between glioblastoma ECM and suppressive MDSC and TAM to find new potential treatment targets. Challenge the project addresses MDSC/TAM and ECM are thought to support tumour growth. However, the impact of ECM on TAM/MDSC and the way ECM and immune cells shape glioblastoma’s tumour environment are not fully understood. Furthermore, whether ECM and TAM/MDSC can be targeted to help patients with glioblastoma remains unclear. I believe that understanding the role of ECM and TAM/MDSC in brain tumours could pave the way for new treatments for glioblastoma. Aims and objectives This project aims to define the effect of ECM on TAM and MDSC in glioblastoma by addressing the following objectives: Determine the relationship between ECM, TAM/MDSC, and survival. Identify mechanisms by which glioblastoma ECM influences immune cells. Test if altering the tumour’s ECM can restore cancer-fighting immune responses. A key feature of my work is exclusive use of glioblastoma patients’ cells in experiments to confirm if specific ECM patterns drive the emergence of immunosuppressive MDSC/TAM. Methods Aim 1: The molecular structure and composition of glioblastoma ECM will be determined by taking high-resolution pictures of tumour specimens with an innovative technology called 3D-OrbiSIMS. These same specimens will next be stained to determine the location of subsets of immune cells. These two sets of data will be brought together to understand how the pattern of ECM molecules relates to immune cells in the tumour. Aim 2: Glioblastoma cells obtained during surgery or ECM produced by these cells will be cultured in the laboratory with healthy immune cells.  This will allow us to better understand aspects of glioblastoma and ECM that drive normal immune cells to become MDSC/TAM. Aim 3: The ECM pattern of glioblastoma cells will be changed with specific drugs before adding immune cells. Drugs will be selected to reflect changes in ECM identified in previous experiments. Potential applications/benefits Data obtained from this project will help identify ways in which ECM and TAM/MDSC can be targeted to boost anti-tumour immune responses, which may lead to new treatments for patients with glioblastoma. Wei https://doi.org/10.1186/s12885-024-12751-3 Popova https://doi.org/10.3390/cancers14010238    

UKRI Gateway to Research · FY 2025 · 2025-11

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of chronic liver disease, posing significant health and economic challenges. One in 5 people in the UK are estimated to be affected by MASLD, and in 2019, the total global cost of MASLD and its complications—such as cirrhosis, and liver cancer—was estimated at $1 trillion. MASLD is considered a multi-system disease and results from a complex interplay between metabolic processes involving lipid metabolism, synergy between excess weight and liver damage, abnormal insulin signalling, inflammatory responses, and alterations in gut health, all of which are influenced by the genetic makeup of individual patients. This complexity makes MASLD a difficult disease to understand and treat. The absence of reliable human-relevant models that replicate the multifaceted nature of MASLD has hindered the development and testing of effective treatments. Recent studies show that most animal models fail to adequately represent key features of MASLD in humans, underscoring the urgent need for more accurate human-based models. This gap has spurred growing interest in the development of tissue models in the lab. However, challenges persist, such as unreliable cell sources, the lack of immune system functionality in these models, limited reproducibility, and difficulties in capturing the full complexity of the disease, including organ interactions and patient-specific factors like genetics. Our proposal aims to address these challenges by using peripheral blood cells from well-characterised men and women with MASLD to differentiate pluripotent stem cells. These stem cells will be used to develop immunocompetent models of three key organs involved in MASLD: the gut, liver, and adipose tissue. These organ micro-tissues developed using cells from the same individual (a unique advantage of using pluripotent stem cells) will be housed in small bioreactors that recreate their natural environments and facilitate the connection between them, mimicking their interactions within the human body. By studying these interconnected tissue models, we aim to explore how the gut, liver, and fat tissues interact in the development of liver fibrosis in MASLD and evaluate potential treatments. We will utilise cells from patients with MASLD of Caucasian and South Asian descent, who exhibit distinct disease presentations and divergent treatment responses. This will allow us to benchmark our model against clinical data, representing a critical step toward validating these in vitro models for academic and industrial drug discovery and testing. We believe that incorporating both the metabolic and inflammatory aspects of MASLD will allow for a more accurate representation of disease pathology, including the modelling of liver fibrosis—a key feature that current models do not replicate. Furthermore, we hypothesise that models derived from patients with different ancestries and genetic backgrounds will exhibit varied responses to treatments, mirroring real-world patient outcomes. Demonstrating these differences will enhance the credibility of this new disease model, fostering its adoption by researchers, clinicians, and the pharmaceutical industry in the investigation of MASLD pathophysiology and the development of novel therapies. This project builds on our expertise in scalable culture methods, stem cell-based organ models, organ-on-chip technology, clinical hepatology, and drug discovery. The platform we develop will be a valuable resource for researchers, industry professionals, and clinicians working on complex diseases, and aligns with emerging regulations such as the FDA Modernization Act, which supports the use of organ-on-chip models to replace animal testing.

UKRI Gateway to Research · FY 2025 · 2025-11

Unstructured text, like a social media post or a newspaper article, is not organised into a predefined format.  These documents are typically narrative in nature and written in free-text.  If they contain confidential or personally identifiable information, they are classified as being sensitive unstructured text.  Examples include referral letters from GPs to specialists, discharge summaries after hospital stays, police reports, court transcripts and work emails.  To make sensitive data easier to analyse with computers they can be structured, which means they are organised into a standard database model and coded using identifiers which make it easy for computers to understand the data.  Structured sensitive data can be accessed by researchers using Trusted Research Environments (TREs). TREs are highly secure computer systems where sensitive data is stored, de-personalised and then made available for approved researchers to analyse within a secure virtual environment. Federated analytics is a system where the data does not move from the TRE, and instead the computer code the researchers write is sent to the TRE.  Currently, TREs do not have any capabilities to make unstructured text available for federated analytics.  The TRExt project will enable TREs to convert sensitive unstructured text into a structured format so it can be easily used in federated analyses. Software already exists for handling the individual steps involved in finding useful information in health-related text and loading it into a standard database model.  The first step involves extracting clinical information from the text.  This can include things like medications a patient is taking, their diagnosis, and any operations they may have had.  The second step is to convert the information into a format that a computer understands and store it with lots of other information in a standard database model that is designed for a particular type of analysis.  The TRExt project brings together the experts responsible for making these software components to work together to assemble them into a reusable pipeline that can be used by TREs.  In this project only publicly available anonymised clinical text data and fake computer-generated text data will be used, so there are no privacy risks. Our work will comply with the UK “Five Safes” principles which ensure TREs handle data safely.  To ensure our work will be applicable to many TRE owners, we will align with the DARE UK Transformational Programme to deploy our demonstrator within their existing infrastructure for TRE federated analytics, called TRE-FX.  The public must have confidence in the approaches we develop to enable computers to process and understand human-readable documents for research purposes.  Our public involvement and engagement (PIE) activities will open our technical methodologies to scrutiny by members of the public and capture public trust and concerns that will influence our design decisions.

UKRI Gateway to Research · FY 2025 · 2025-10

Blood cancers such as Acute Myeloid Leukaemia (AML) are challenging to treat. Around 3000 adults and children are diagnosed in the UK each year and survival is variable, but overall poor. Relapse is the most important singular cause of treatment failure in AML. This project asks how we can prevent relapse. In AML, primitive blood cells grow out of control in the bone marrow and blood. Chemotherapy is used to kill these cells. Some dormant cancerous cells, called leukaemic stem cells (LSCs) are not killed by chemotherapy, but can start growing again later when they receive the right signal. Reactivation of LSCs after patients achieve remission leads to relapse, typically with an even more aggressive and difficult to treat cancer. We do not know why LSCs begin to grow again and because they are rare, they are difficult to study. There are currently no treatments specifically targeting LSC regrowth. Some patients continue to have low levels of cancer cells in their blood and bone marrow after treatment, which is associated with a higher chance of relapse and requires monitoring with regular bone marrow samples. Whether these cells are always dormant LSCs capable of causing relapse or other, residual cells which cannot cause relapse is unknown. This lack of understanding can lead to missed treatment opportunities or unnecessary, risky, and expensive bone marrow transplantation. Relapse is therefore difficult to predict, prevent or treat. AML is caused by a variety of genetic mutations leading to different AML subtypes which behave differently. In one type of AML, known as t(8;21), around 50% of patients relapse and circulating blood cancer cells often remain after treatment. We have shown that the signals which activate the growth of t(8;21) LSCs are the VEGF and IL-5 pathways, which act via the signalling responsive AP-1 transcription factor family. These pathways are not normally active in healthy blood stem cells, but are switched on in t(8;21) LSCs as a result of the AML-causing mutation. Due to the specific gene expression patterns caused by each genetic mutation, we hypothesise that there will be other AML subtype-specific pathways which lead to LSC reactivation. To find which signals could activate LSC growth in AML subtypes other than t(8;21), we will carry out single cell RNA-sequencing to examine gene expression in sorted LSCs from patients with three further molecular subtypes. We will use this to identify which growth factor pathways are LSC-specific in each type and perform functional assays to test if they activate AP-1 and promote growth. Where available, inhibitory drugs of these pathways will be used to test if LSC reactivation can be prevented. Newly transcribed genes from the LSCs will be captured following stimulation of the identified growth pathways. Integrating this information with our single cell sequencing data will let us identify precisely how LSCs begin to grow by finding which genes are activated. In parallel, the aberrantly expressed growth pathways will be used to improve existing methods for detecting cancerous blood cells and predicting relapse, by measuring only those cells which will go on to cause AML regrowth. Together this program of work will produce: LSC-specific therapeutic targets to block growth and prevent relapse. A platform using these novel, functional biomarkers to predict relapse more accurately. Mechanistic insights into how the relapse causing LSCs grow.

UKRI Gateway to Research · FY 2025 · 2025-10

Modern life revolves around contracts and legal agreements. Yet large segments of the population do not understand them, exposing vulnerable groups to undue risk. More specifically, legal documents abound in everyday life – from credit agreements to insurance policies and mortgages. In the UK, regulators have implemented measures to reduce the risk of harm to consumers by mandating that companies use clear and accessible communication (e.g., Financial Conduct Authority’s Consumer Duty regulation). Thus, companies must provide clear and accessible legal documents to ensure regulatory compliance, as well as to avoid reputational damage and/or fines. However, literacy levels in the UK mean that many people will not understand legal documents nor their implications. Our company – CommCheck – enables companies to comply with regulations and to provide their own downstream customers with a better user-experience. CommCheck is a readability solution that empowers companies to draft legal texts for their customers in accessible language. Other readability tools are available that involve ‘count measures’ (e.g., counting word and sentence length) have been available for decades (e.g., Microsoft Word offers a basic tool). These are easy to ‘game’ by using short words and sentences (e.g., “doff” elicits better readability than “remove” because it is shorter). Alone, these tools are therefore inappropriate. AI solutions provide text simplification. However, explainability, reproducibility, enforceability, context and maintaining business intent are major failures of current A1 tools. Also, AI solutions cannot use specialized words reliably and plain English does not ensure that legal precision is maintained. AI solutions also present data privacy and confidentiality concerns. CommCheck is a research-backed solution that incorporates data about what words people know, how difficult they are to process, as well as data from reading in real-world contexts. CommCheck has been developed by world-leading experts to ensure that our solution offers accuracy and performance which exceeds competitor products.