University of Manchester

UKRI Gateway to Research · FY 2026 · 2026-01

Immune responses to pathogens are essential for human health. After seeing pathogens for the first time, our immune system can remember this encounter and respond to re-infection with the same pathogen more effectively. This process, termed ‘immunological memory’, is vital in allowing us to deal with repeat infections, and is also the cornerstone of successful vaccination. Key cells in promoting memory responses in the immune system are T-cells. These cells are activated during initial infection, with most dying off when the infection is cleared, but some becoming long-lived memory T-cells that respond more quickly and effectively to re-infection. Understanding how memory T-cells function is therefore crucial in understanding how we successfully fight infection, and in the design of vaccines to promote immunological memory. Our exciting new data has identified an unexpected role for a subset of memory T-cells in regulating responses to re-infection. Thus, a proportion of T-cells previously classified as CD4+ effector/memory T-cells have the ability to activate the cytokine TGF-beta and play an unexpected role in keeping the brakes on the T-cell response during viral re-infection in the lung. In the absence of this pathway, more damage occurs in the lung during re-infection. Thus, we have uncovered a pathway that appears to limit the immune system during re-infection to prevent unwanted inflammation and tissue injury. It is now critical that we determine in detail the properties and characteristics of these cells, why they are specialised to suppress tissue damage during re-infection, and whether they function during specifically during viral re-infection in the lung or to other immune challenges as well. Additionally, we have discovered that these suppressive memory T cells are present in tumours, where they may play roles in suppressing anti-tumour immune responses. The overarching aim of this project is to investigate how a newly identified sub-population of CD4+  T-cells regulate immune responses to lung re-infection and determine the broader importance of this pathway in other tissues, and cancer. This will be achieved via the following three aims: Aim 1: Investigate the molecular, functional, and spatial characteristics of suppressive CD4+ effector/memory T-cells that limit immunity during lung re-infection. Aim 2: Determine the broader role of suppressive CD4+ effector/memory T-cells in inflammatory challenge. Aim 3: Examine the role of suppressive CD4+ effector/memory T-cells in regulation of cancer immunity. The enhanced understanding generated will provide fundamental insights into how immunological memory is regulated to help us balance responding robustly to pathogens upon re-infection without causing tissue damage. Our work will also determine other situations where these pathways act and could be targeted in disease or exploited therapeutically – for example targeting these cells to enhance immune responses in cancer.

UKRI Gateway to Research · FY 2026 · 2026-01

Cities are the focal points of human and infrastructural vulnerability to climate-related hazards. They are also pivotal in implementing climate mitigation and adaptation policies. Thus, better representation of urban areas in numerical models is essential for improving large-scale predictions of local urban climates and developing effective adaptation strategies. However, urban areas currently remain underrepresented in global-scale Earth system models (ESMs). As one of the ESMs that resolves urban representation and physical processes, the Community Earth System Model (CESM) represents cities into three basic types (built types): tall building district (TBD), high density (HD), and medium density (MD), based on LandScan 2004 population density data. This simplified representation of built types and the accompanying urban surface data do not effectively capture the complexities of urban environments, thus compromising the accuracy of future climate projections and evaluations of climate adaptation strategies. This project aims to incorporate the local climate zones (LCZs) classification system—a system widely used in observational/measurement-based urban environment studies—into Earth system modelling. LCZs provide considerable potential to improve the representation of urban areas within numerical models, but their potential is as yet untested in a global model. Specifically, we will develop global-scale LCZs-based urban surface data based on 10 urban built types, create the "LCZs scheme" for the CESM, and evaluate LCZs-based urban climate projections (e.g., urban 2-m air temperatures over the next 50 years) along with the effectiveness of adaptation strategies (e.g., implementing white roofs). The project is structured into three Working Packages (WPs), each aligned with a specific objective to ensure both effectiveness and appropriateness in achieving our goals. All methods, models, data, and research outputs will be made freely accessible, aiming to maximize the translation of our outputs into significant outcomes and widespread impacts for various end-users (e.g., from model developers to community stakeholders). WP1 focuses on developing and integrating local climate zones-based global urban surface parameters into the Community Land Model – Urban (CLMU), the urban model within the land component of the Community Earth System Model (CESM). WP2 will develop the LCZs scheme into the CESM and validate the simulations with various configurations. WP3 involves urban climate adaptation modelling with an emphasis on urban surface albedo modification. This high-risk, high-reward initiative could disrupt current models, requiring extensive validation, but by doing so promises transformative insights into global urban climates. The tool will align with observational studies and provide valuable data for other community models. It aims to improve understanding of urban heat islands and climate extremes, and aid in developing urban climate adaptation strategies. Beneficiaries include the urban climate modelling community, urban planners, and policymakers, who will gain access to enhanced modelling tools and data for developing resilient and equitable urban strategies.

UKRI Gateway to Research · FY 2025 · 2025-12

When successful, this work will enable a step change in our approach to bowel cancer treatment by developing miniaturised soft robots for regiospecific localisation of drugs in malignant tissues. Inspiration for this challenge will be taken from snails and slugs which have evolved a unique form of slime-based locomotion that uses muscular undulations in a single 'foot' combined with an adhesive mucus to propel their bodies. This locomotor mechanism allows these animals to move precisely at very slow speeds through a wide variety of environments and this form of locomotion is of great interest in terms of both its evolutionary biology and as a model for bioinspired robotics. Our hypothesis is that the actuation, sensing, and control strategies adopted by snails can be exploited in soft robots to enable regiospecific controlled release of drug cargo, whilst withstanding the physical, chemical, and mechanical stresses within the physiological environment. This localisation approach will enhance the bioavailability of anti-cancer treatments in tumour sites and minimise off-site side effects of these toxic drugs. However, work on snail-inspired robots has been limited up to now, both because the biomechanics of snail locomotion itself is not well understood and also because there has been limited scope for either simulation or construction of such robots. Therefore, a prime goal of this project is to address these shortcomings. The project will study snail locomotion and develop models to produce snail-like simulations, including foot movements, interactions with mucus, and machine learning options for control. Snail-inspired soft robotic prototypes will be built to showcase the concepts developed through simulations and provide the essential ground-truthing. Suitable actuation and control options will be assessed for implementation using novel peptide-based soft bionanomaterials that are inspired from natural proteins, hence are bio-functional, biocompatible, and highly tuneable. Using rational molecular design, these materials will be engineered to respond to biofriendly external triggers enabling non-invasive remote control of the soft robots. The project workflow is arranged around the themes of biomechanics, bionanomaterials, robotics, digital twins, and cancer biology, with the specific objectives to: (1) study the locomotion, actuation, and control of snails through detailed experimental measurements under controlled conditions; (2) exploit recent advances in bionanomaterials to develop novel biocompatible materials for soft robots; (3) design and build functional snail-inspired soft robots suitable for drug delivery; (4) develop a multiscale digital twin simulation framework to support engineering and biological research in cancer treatment; and (5) demonstrate soft robotic prototypes that can aid the treatment of colorectal cancer. The project is significant because it will deliver detailed data on snail biomechanics that is new to science and use this to accelerate the discovery of novel robot control strategies and kinematic configurations. We will produce new bioinspired micro robotics-based devices for the controlled and precise localisation of drug cargo in malignant tissues. This innovative approach has significant impact as it will overcome some of the main limitations of the current clinically used drug delivery systems by enhancing selectivity and bioavailability and minimising off-site side effects. Furthermore, there will be broader impacts both within the biomedical field, e.g., as an alternative to techniques such as capsule endoscopy, and on future development of microrobots beyond the biomedical field, e.g., in applications from pipe inspection and cable laying to advanced agri-food and pollution control.

UKRI Gateway to Research · FY 2025 · 2025-12

Recent years have further revealed the depth of inequality in UK cities, including in relation to race and unequal access to the elusive identity of 'Britishness' in the context of polarized attitudes towards migration, asylum and the UK's imperial past. The experience of Somali diaspora - among the UK's most stigmatized and misunderstood but resourceful communities - throws these issues and the broader challenges of post-Brexit, pandemic Britain into sharp relief. The UK Somali experience sits at the intersection of local and global challenges in ways that are emblematic of contemporary questions of race, refuge and unequal citizenship in the context of problematic ideas of 'integration'. Moreover, the lives of UK Somali communities are often highly transcontinental, with patterns of investment and political engagement in the 'homeland', and the reality or aspiration of 'return', shaping their relationship with the UK and the British state. The Somali experience of life in UK cities is thus intimately connected to development processes in Somalia, and vice versa. Consequently we need to think about policy in more connected ways too, spanning the divides between local communities policy and international development policy. This project will analyse these intersections. It frames the British Somali experience of urban citizenship in relation to the varying 'faces' of Britain both locally and globally, through research in three very different cities that illustrate diverse aspects of the UK's urban political geography and have different roles in Somali migration histories: Sheffield, Bristol and London borough of Camden. This is supplemented by research with returnees and transcontinental communities in Somalia/Somaliland. It combines an interdisciplinary approach drawing across urban studies and development studies with a collaborative, partnership-based design, drawing in civil society partners including the Refugee Council, City of Sanctuary, the Council of Somali Organizations and local Somali community-based organizations in all three cities. The research aims to explore: i) the experiences of multigenerational Somali communities in UK cities in terms of exclusion, representation, service access, aspirations and inter-community engagement; ii) how this relates to changing transcontinental networks and developments in Somalia; iii) how UK policy both globally and locally feeds into the Somali diasporic experience and capacity to manage recurrent crises; and iv) how a better understanding of these dynamics could foster enhanced urban citizenship and solidarity, and improved policy across a range of domains. Through engaging local and national partners and government at different scales, the project will generate new avenues of cross-sectoral dialogue, practitioner guidance and opportunities for research-led civil society activism. Moreover, as Somali refugees were the first significant incoming refugee group in the post Cold-War era, a long-term view on their experiences holds important lessons for present and future refugee experiences. The project will therefore put the research findings relating to the experience of Somali diaspora in conversation with the needs of more recent refugee arrivals, taken forward through project partnerships with the Refugee Council and City of Sanctuary. The overarching vision of this project is to deepen knowledge on the interdependence of global and local challenges through this focus on the urban experience of multigenerational Somali refugee diaspora, in order both to build inter-community solidarity and contribute to improved coherence across relevant policy domains. It offers fresh lenses on interconnected problems through a transcontinental research programme involving sustained inter-sectoral modalities of working, novel forms of multi-sited and interdisciplinary research, and a collaborative plan for impact and knowledge exchange predicated on deep community engagement.

UKRI Gateway to Research · FY 2025 · 2025-12

Lysosomal storage disorders (LSDs) are a heterogeneous group of rare heritable diseases caused by defects in lysosomal function which result in a gradual accumulation of substrates and to cell and tissue dysfunction. Despite a related aetiology, LSDs show disease-specific organ involvement and considerable patient-to-patient disease variability. This research will focus on understanding Fabry disease (FD) as an exemplar LSD. FD is a multi-organ disorder which by early adulthood frequently displays heart and kidney involvement. It is caused by mutations in GLA encoding the enzyme a-galactosidase A (a-gal A) which breaks down the glycosphingolipid Gb3, but the molecular cascade downstream of this defect remains opaque. As with many LSDs, clinicians have the challenge of managing different disease subtypes and presentations, gene variants of unknown significance (VUS), and unpredictable disease life courses. For FD, the major treatment options, enzyme replacement therapy (ERT) and chaperone therapy (for amenable mutations) can slow disease progression when initiated at an early stage, but each has limitations. Evidence of inadequate efficacy for ERT in heart and kidney is of major concern — lipid accumulation in these organs is a cause of tissue fibrosis and related cardiac arrhythmia, functional decline and organ failure. Delivering more personalised, accessible and efficacious therapies is an urgent priority for increasing the healthspan and quality of life of patients. This research aims to improve our understanding of the pathogenic mechanisms and patient variability of FD using induced pluripotent stem cell (iPSC)-based models, supporting progress towards ‘precision medicine’ for this disease and by extension for other complex inherited conditions. In advance of this application, our privileged access to the largest cohort of FD patients in Northern England enabled us to generate four FD patient-derived iPSC lines, providing the opportunity to address these aims expeditiously supported by a leading physician in the field. A major challenge of in vitro disease modelling is to accurately recreate disease phenotypes which take years to develop in patients. To tackle this, our first goal will be to identify and experimentally limit compensatory mechanisms to enhance the rate of Gb3 accumulation in FD cells. These efforts will focus on lysosome regulating proteins LIMP-2 and Cx43, both of which can become elevated downstream of a-gal A dysfunction. By generating 3D in vitro tissue models of heart, kidney and lung using organoid technologies, we will be able to study multiple organs and cell types impacted by FD. Since the immune system is a major contributor to LSDs and may drive the development of fibrosis and organ failure in FD, we will incorporate iPSC-derived macrophages into the organoids. Comprehensive structural characterisations together with proteomics and single cell RNA sequencing (scRNA-seq) will enable us to discover mechanisms of disease, pathogenesis-associated gene regulatory networks and potential causes of patient variability in organ involvement and age of onset. We will also discover novel cell type- and stage-specific disease biomarkers of potential clinical value. The approach is scalable and highly transferable to other inherited diseases. Moreover, these models will serve as platforms for drug and gene therapy testing, including gene correction technology. Together this research has the potential to deliver better patient stratification and to widely unlock therapeutic opportunities.

UKRI Gateway to Research · FY 2025 · 2025-12

Air pollution is a pressing concern for those living with its effects and policymakers working to address it. Exposure to polluted air is shaped by inequalities, linked to poor housing, geography, and occupation; it raises significant health, social, and environmental challenges. However, responses are limited by fragmented data, research siloed within separate disciplines, and approaches that fail to capture air pollution’s full complexity. Our project takes a new methodological and theoretical approach to the challenge of how to understand air quality in all its multiple dimensions and centres people’s everyday experiences. We develop an interdisciplinary concept of air inequalities, integrating community experiences and activisms, scientific air quality measurements, and understandings of local environments. The methodological shift we propose pays attention to how data is generated and ways of integrating these methods (air sensor technology, how community activists and qualitative/creative methods ‘get the measure’ of a place as polluted). Air is simultaneously scientific, social, cultural, and political. Addressing it requires an interdisciplinary response. We bring together different disciplinary methodological and theoretical expertise: atmospheric sciences’ (AS) scientific air measurements, social work’s (SW) community co-production, heritage studies’ (HS) holistic community centred understanding of environments, science and technology studies’ (STS) on how people use/understand air sensor technology and sociology on inequality and everyday lives. By integrating these, the project offers methodological and theoretical shifts to inform both policy and everyday practices, centring community concerns. Based in Manchester, where air pollution is often five times above WHO guidelines (PHE 2019), the project uses a place-based, immersive approach that is essential to produce a multi-faceted understanding of air quality. Manchester’s challenges (transport, lack of green spaces, poor housing) are shared by many cities, making our methods and conceptual framework scalable and transferable. Project aims: 1.      Develop a new understanding of air quality that integrates different disciplinary ways of knowing about air through interdisciplinary dialogues 2.      Establish a conceptual framework of air inequalities, incorporating the relationship between domestic and outdoor air in multiple urban spaces. 3.      Evaluate current air quality measurement methods and recommend changes to ensure they are accurate, accessible, and relevant to different groups/disciplines. 4.      Strengthen community approaches to air quality, supporting local efforts to articulate concerns and engage more effectively with academia and policy. This research builds on a pilot project co-produced with communities, whose concerns shaped this project, which we have framed through four methodological Facets (drawing on Mason’s facet methodology, 2011). Using methods from multiple disciplines, walking interviews, guided walks, sketching and mapping, and indoor and outdoor air quality sensors, we explore different ways of ‘getting the measure’ of air. Key outcomes: A new concept of air inequalities that integrates community experiences with academic ways of understanding poor air to offer a transferable interdisciplinary approach. A shift in how academics and policymakers conceptualise and respond to air quality and air inequality. Sustained collaborations between academics, community groups, and policymakers, disrupting existing hierarchies and promoting inclusive practices. New frameworks for heritage professionals and communities to value and look after local environments through the lens of air. Development of technological community literacy in using trusted air quality technologies, enabling communities to make credible claims and influence over policy and behaviour. Reference: PHE. 2019. Public Health England; ‘Review of interventions to improve outdoor air quality and public health’.

UKRI Gateway to Research · FY 2025 · 2025-12

MicroRNA, ‘a small RNA molecule with a big mission’, has been recognised by the 2024 Nobel Prize award for its huge role as a master regulator of the expression of genes by inactivating the translation of messenger RNAs into proteins. When regulation by microRNAs becomes dysfunctional, serious diseases are triggered, including inflammatory diseases and aggressive forms of cancer. Indeed, excessive expression of “oncogenic” microRNAs are linked to human tumour transformations. Destroying these oncogenic miRNAs can reverse cell functions from “diseased” to “normal”. We have demonstrated specific and potent destruction of these oncogenic microRNAs in cells and tumours by a smart peptide–DNA molecule. We engineer the smart molecule as a catalyst to work like an enzyme, to bind and destroy many copies of target microRNA, by carefully linking a short piece of DNA (to recognise and bind particular microRNA sequences) to catalytic peptides (to breakdown the bound microRNA for recycling). Our smart catalysts work on their own, but crucially also work in synergy with the biological machinery inside cells to boost the speed of microRNA breakdown in cells and reduce their half-life by more than 150-times. This has put aggressive diseases within scope of our approach. Even the oncogenic microRNAs, which are rapidly produced in the most aggressive cancer cells, are knocked back down by these smart catalysts to reverse cells to their normal functions. A single dose of such peptide–DNA molecules was disease-modifying: it suppressed the malignant properties of cancer cells and inhibited tumour growth over weeks. However, these catalytic agents are rather unstable in cells and tissues, because the DNA used in our smart molecules (to recognise and bind harmful microRNAs) is degraded by cellular enzymes in body fluids within hours. The poor biological stability of these (currently unprotected) smart catalysts poses the main risk for transforming them into future therapies. In this project, we shall protect our microRNA-inactivating molecules from rapid biological degradation by shielding their most vulnerable parts with chemical alterations. This will make them resistant to cellular enzymes and increase their survival in the body considerably. We understand, of course, that any structural alterations may not only affect the “enzyme-like” properties of our smart catalyst, but also endanger its crucial synergy with cell machinery.  It is important therefore that not only the biological stability in serum, but also both the catalytic and synergistic activities of the protected forms are measured in this project. Fortunately, we have years of extensive experience working with these microRNA-inactivating catalysts, which allowed us to find the best structural designs most likely to retain and even increase their “enzyme-like” action and synergy with cell machinery. Solving this “high-risk” factor (i.e., “biological instability”) will also boost the overall potency of the protected smart catalyst by increasing its survival time in body fluids, so that more of the dose reaches the target, and the knock-down continues to work for much longer to combat the rapid over-production of fresh microRNA in aggressive diseases with limited or no therapeutic solutions. Of many such unmet clinical needs, we chose knock-down of one of the most aggressive metastatic cancers (Triple-Negative Breast Cancer) as the demonstrator of success.

UKRI Gateway to Research · FY 2025 · 2025-12

Artificial Intelligence (AI) is rapidly changing how scientific research is conducted, offering tools that can assist with tasks such as literature reviews, data analysis, and even writing. However, we still know very little about how the adoption of AI is actually shaping the behaviours, outputs, and career paths of researchers. This project aims to fill that gap by investigating how AI has transformed academic knowledge production. This research focuses on the biomedical sciences, a field of critical importance for public health and innovation, and will explore how AI tools are being adopted by scientists at different stages of their careers, as well as the impact of AI adoption on scientists’ productivity, creativity, research diversity and career trajectories. For example, it will look at whether junior researchers—who may be more digitally fluent—are quicker to embrace AI than their senior counterparts, and whether this leads to more equitable research outcomes or widens existing gaps. The study will pay particular attention to differences across gender, career stage and institutional affiliation, to understand whether AI acts as a leveller or deepens inequalities in academia. To do this, the project will draw on large-scale publication data (using sources such as PubMed knowledge graph and Open Alex). Additionally, a specific case study comparing PhD graduates in the UK and Japan based on large scale dissertation data will offer international insights into how AI is affecting doctoral training. The aims of the project are threefold. First, it will advance the growing field of metascience by providing robust evidence on how AI affects research productivity, creativity, diversity, and the career trajectories of scientists. This will involve using state-of-the-art AI tools—particularly large language models and Generative AI—not just as objects of study, but as methodological instruments to analyse large-scale scientific datasets. By using AI to study AI, the project will explore the capabilities and limitations of these models in extracting meaningful patterns from scientific texts, enabling novel forms of analysis that go beyond conventional bibliometric techniques. Second, the project will develop new conceptual and analytical frameworks to understand how AI influences the organisation of scientific work—shaping collaboration networks, the adoption of new research methods, and the evolution of research agendas. Third, it will generate actionable insights to inform the design of more inclusive, human-centred AI tools. By identifying adoption patterns, and demographic disparities, the project will assess whether current AI systems adequately support diverse researchers and research settings. The findings will be relevant to universities, research funders, and policymakers who are seeking to understand and guide the responsible integration of AI into science. They will be shared through high-profile academic publications and conferences and translated into practical recommendations for research institutions and policymakers. Insights from this project will be disseminated to relevant stakeholders, including the Greater Manchester Combined Authority (GMCA), DSIT government office for science (Go-science), to ensure the results contribute to digital inclusion, talent development, and responsible innovation. Ultimately, this research will improve our understanding of how AI is reshaping the nature of scientific work. It will offer new tools and evidence to support more equitable and effective use of AI in research, helping to ensure that its benefits are widely shared and that the next generation of researchers is equipped to thrive in an AI-driven world.

UKRI Gateway to Research · FY 2025 · 2025-12

Approximately 600,000 people die each year in the UK (ONS, 2021). The term ‘death administration’ is used to describe the tasks that must be completed after someone dies, such as notifying officials, dispersing belongings, and managing probate (including property sales, asset management, and inheritance distribution). In 2022 the UK Commission on Bereavement found that 61% of adult respondents struggled to deal with these time-consuming and time-sensitive administrative responsibilities, yet the toll of this remains largely invisible with academic literature tending to focus its analysis on emotional support in the aftermath of bereavement. Such oversight belies how structural inequalities, as research has shown, exist in certain bureaucratic procedures, leading to the existence of issues such as funeral poverty. Beyond funerals there are other significant forms of latent inequality, embedded across wider death administration processes, that have yet to be recognised or explored. For example, to what extent do bereaved individuals have equal access to the (material, social and emotional) resources needed to complete essential administrative tasks (from making bereavement support claims to closing bank accounts)? How are individual experiences affected by unequal levels of technological access and digital literacy? Who is expected and allowed to complete death administration tasks according to state and corporate policy, and how do these restrictions impact upon the experiences of those bereaved? Death administration processes can add significant distress to people in an already vulnerable emotional state and have the potential to reinforce as well as create new forms of social inequality. It is imperative therefore that this subject receives further academic investigation. Building on findings from the PL’s pilot study, the proposed project uses an innovative methodology to produce a pioneering qualitative analysis of the relationship between death administration and under-recognised forms of inequality. In doing so, we will create a step-change in how we think about and research inequality, emphasising how lesser recognised manifestations of inequality can significantly impact people’s lives and experiences in the context of death, dying and bereavement. Working in collaboration with a range of external organisations over the three-year project (including formal research partner the National Bereavement Service) as well as state departments, and corporate and charitable stakeholders (including the Department for Work and Pensions, Octopus Legacy, and Cruse Bereavement Care), we aim to establish the extent to which death administration processes create or reinforce experiences of inequality, and outline recommendations for ways to improve current policy and practice. By working with these stakeholders, we aim to streamline death administration procedures across public and private organisations, improve knowledge of systems and requirements, and help reduce the substantial administrative burden placed on those bereaved. Application of information gathered will be developed in discussion with a range of relevant stakeholders, as we collaboratively aim to improve the mental health and wellbeing of bereaved people across the UK. Objectives Use policy mapping to produce a detailed and accessible understanding of current death administration requirements and processes. Informed by the empirical work in objective 1, use qualitative research methods, including interviews and open-ended surveys, to produce a detailed and accessible analysis of the hidden inequalities inherent within, and caused by, death administration. Drawing on the outputs generated by objective 1 and 2, create new frameworks for policy and practice that support better mental health and wellbeing outcomes for those bereaved.

UKRI Gateway to Research · FY 2025 · 2025-12

The proposed work is an original research project with two main objectives: (1) to provide a generalised mixing theory for shear-induced dispersion and (2) to test the theory by applying it to four iconic mixing problems. The theory is pertinent to many engineering and real-life situations involving transport phenomena with variable density, viscosity, and other transport properties. Such situations are encountered in a variety of contexts with vastly different length scales—from the oceanic to the microscopic. The project is an ambitious attempt to generalise theoretical concepts and tools recently developed in our combustion-focused investigations in order to develop a theoretical framework with broad interdisciplinary applications. The theory will be applied to the following four problems: Flame instabilities in a Hele-Shaw cell, focusing on the coupling between Taylor dispersion and classical instabilities associated with variable properties, including the Darrieus–Landau instability (associated with variable density), the Saffman–Taylor instability (associated with variable viscosity), and the diffusive-thermal instability (associated with unequal mass and heat diffusivities). In the project, specific emphasis will be dedicated to hydrogen combustion. Effect of Taylor dispersion on the Rayleigh–Benard instability (associated with buoyancy)  in a Hele-Shaw cell.  Effect of Taylor dispersion on the  double-diffusive convection instability (associated with buoyancy and differential diffusion) in a Hele-Shaw cell. Effect of Taylor dispersion on the Marangoni convection (associated with variable interfacial surface tension) in a thin fluid layer.  The objectives of the work will be accomplished through a two-phase approach, the first being based on theoretical tools such as scaling analyses and perturbation methods  and the second relying both on  theoretical tools such as modelling and linear stability analyses and numerical tools involving  numerical computations applied to the four selected problems. The success of the project will pave the way for future proposals that will benefit various beneficiaries. Such beneficiaries include applied mathematicians, fluid dynamicists, combustion scientists, oceanographers, physiologists, and others. A concrete illustration of research areas on which the project is expected to have an  impact is that of hydrogen combustion, to which one of the test problems in this proposal is dedicated. Specifically, the outcomes of this problem should contribute to improving our understanding of hydrogen-flame dynamics in micro-engines that can power devices such as micro air vehicles (MAVs) and micro-satellites, thereby assisting engineers to design these devices more efficiently. With hydrogen being regarded as one of the most promising fuels for the future in order to decarbonise current fuels, this research should contribute to placing the UK at the forefront of international research efforts to address global greenhouse gas concerns. This is also in line with the EPSRC's strategic plan towards achieving "engineering net zero" via "transformative low and zero carbon—hydrogen and alternative liquid fuels".

UKRI Gateway to Research · FY 2025 · 2025-12

This project will replace the University of Manchester’s (UoM) end-of-life 7T preclinical magnetic resonance imaging (MRI) scanner with a new cryogen free state-of-the art 7T instrument. MRI is best known for its use in hospitals to diagnose and monitor diseases of the brain, heart, joints, liver and digestive system. However, it is also an essential research tool used in a preclinical and clinical setting to study how diseases occur, how they develop, and to evaluate novel interventions. In preclinical research, it is used to study disease processes and drug effects in mice and rat models of human disease, as well as to undertake basic methodological research (e.g. developing new MRI techniques). The translational impact of MRI can be significant, since any new method or scientific discovery arising from the use of MRI in a preclinical setting (e.g. diagnostic markers, drug effects), can then be translated to human scanners and tested in a clinical population. Our current instrument is 5 years beyond its serviceable life and was last upgraded in 2008. As such, the instrument is no longer state-of-the-art and is at high risk of non-recoverable failure. Despite these shortcomings, the instrument is highly utilised (~900 hours representing 90% of current operational capacity, underpinning £20M of grant income) and loss of the instrument would kill a wide range of research programmes. This project has two clear objectives: To mitigate the negative impacts associated with failure of our current instrument, preventing loss of preclinical MRI capability at the UoM, To dramatically upgrade software and hardware, boosting image quality and enabling new science not currently possible. The new instrument will enable and enhance a wide range of translationally important studies, from the development of new measurements of cerebrovascular and brain function, to the application of these measurements in understanding the biology of disease and assessment of drug efficacy (see Vision for full details). Upgraded hardware such as higher specification gradients will allow increased brain coverage and spatial resolution for routine as well as novel techniques used within our facility (e.g. filtered exchange imaging, arterial spin labelling, diffusion tensor imaging). This will allow resolution of smaller brain structures involved in cognition (e.g. hippocampus), smaller lesions or anatomies of interest (e.g. perivascular spaces), and to map lesion heterogeneity (e.g. tumour heterogeneity). Stronger gradients will also allow higher resolution imaging of low-frequency nuclei such as deuterium, and higher b-value diffusion MRI enabling kurtosis effects to be measured. Finally, multi-channel coils and improvements in software, particularly SmartMI AI technology, will provide clearer images in less time than our existing instrument, improving throughput. Our existing userbase predominantly use MRI to image the brain. Our longer-term objective will be to expand usage of the new instrument to additional areas including cardiology, capitalising on recent BHF Centre of Research Excellence funding. Automated analysis pipelines will be developed to provide robust and efficient service delivery, reducing barriers to research and increasing throughput, ensuring the instrument is sustainable and continues to deliver impact on the local, national and international stage.

UKRI Gateway to Research · FY 2025 · 2025-12

Artificial Intelligence (AI) is transforming the world and re-shaping multiple occupational sectors, such as healthcare, education, and more. One area where AI is having a substantial impact is scientific research, through presenting entirely new opportunities for sourcing ideas and information, and transforming the skillsets required for producing written academic outputs. Within this, an additional advantage of AI is its potential to create a more accessible and equitable research environment, particularly individuals with ‘Specific Learning Difficulties’ (SpLD), an umbrella term referring to challenges in areas such as reading, writing, and numeracy that include dyslexia, dysgraphia, dyspraxia, and dyscalculia. For whom academic research can pose barriers can include reading comprehension and writing skills, and access to scholarly literature, which may lead to less publications and slower dissemination of research outputs. This may impact career progression and funding opportunities. Individuals with learning disabilities also have a higher risk of burnout due to (i) the barriers stated above, and increased effort required to overcome these barriers and (ii) poorer time management skills and high workloads. This proposal is inspired by my personal experiences with overcoming obstacles and institutional biases related to my learning disabilities. Nonetheless, if implemented correctly, AI Large Language Models (LLM) could be implemented across academic institutions to reduce the inequalities in research output formulation affecting those with SpLD, and help to reduce many of the challenges in this area whilst better managing their workload. Despite the availability of AI technologies and increased use of LLMs worldwide, there remains a gap in knowledge around use of AI and systematically implementing these tools within research institutions to ensure accessibility and usability. This proposal aims to bridge that gap by exploring AI’s role in making research more inclusive and by advocating for policy changes to support AI adoption in academic environments. This project employs a comprehensive mixed methods design to investigate how AI can enhance research accessibility for those with specific learning difficulties. A systematic review will synthesise current literature on AI’s application and impact in academic research, establishing a solid foundation for subsequent studies. An online survey of 300 researchers with SpLD will gather quantitative data on the tools used, benefits realised, and challenges encountered across various research stages, with accessible formats to ensure broad participation. Complementing the survey, semi-structured interviews with both researchers with SpLD and institutional leads will explore in depth the experiences of using AI and uncover barriers and facilitators to its adoption in research. Purposive and snowball sampling will ensure a diverse range of views, enhancing the representativeness of the findings. Experimental case studies employing a within-subject design will compare AI-enabled versus traditional methods across tasks that mirror everyday research activities. These studies will measure improvements in efficiency, accuracy, and workload management through both descriptive statistics and reflexive thematic analysis. Together, these methods will yield robust qualitative and quantitative evidence on how AI can transform research practices for individuals with SpLD. The outputs will include a systematic review, several research papers, and a comprehensive report detailing policy recommendations. Dissemination will be achieved through academic publications and presentations to key stakeholders, including the UK Metascience unit and university equity bodies. Ultimately, the project aims to drive policy change and foster a more inclusive research environment, ensuring that AI adoption benefits researchers across all abilities.

UKRI Gateway to Research · FY 2025 · 2025-11

Hormones are biochemical messengers that are essential to maintain good health. In particular, the hormone cortisol helps protect our body from stressors by reducing inflammation and improving our metabolic, heart and brain function. Interestingly, cortisol levels are never constant, instead, they fluctuate throughout the day, sometimes in response to stressors. When we are not stressed, cortisol is secreted periodically with both an hourly and a daily rhythm. But when we get stressed, the body responds by rapidly secreting additional cortisol on top of these ‘basal’ rhythms. These dynamics are controlled by an endocrine system called the Hypothalamic-Pituitary-Adrenal (HPA) axis, which also works to restore ‘healthy’ hormonal rhythms after a stressor has ceased. From an engineering perspective, the HPA axis can be thought of as a well-adapted dynamical system, one that is highly responsive to a wide range of stressors. However, whilst the body copes well with minor disruptions like skipping a meal or occasionally going to bed late, it finds it difficult to withstand long-term disruptions which can cause hormonal rhythms to become misaligned. This happens for example in shift workers (~15% of the UK workforce, 20-30% worldwide), whose imposed behavioural schedule carries major risks to health. Despite overnight shift work being one of the most common sources of stress, we don’t quite understand how the HPA axis becomes dys-regulated during this and other types of stressors that lead to adverse health outcomes. My Fellowship proposal re-imagines this as a theoretical challenge. If we were able to mathematically understand and predict how certain stressors lead to hormonal rhythm misalignment, then we may be able to design strategies to prevent and reduce the health risks associated to such misalignment. The timing couldn’t be better: recently developed wearable devices such as U-RHYTHM now allow measuring daily hormonal rhythms without the need for blood. On the other hand, conventional wearables can simultaneously collect data from other body rhythms such as glucose, heartbeat, physical activity, and body temperature. These devices have been used to measure daily endocrine rhythms in hundreds of participants, including patients, in real life settings. Taking advantage of these existing human datasets that are unique in the world, I will analyse them using techniques from mathematical modelling, signal processing, statistics, and machine learning. My goals are to quantify variability in hormonal rhythms, determine what makes these rhythms robust to some stressors but fragile to others, and design computer algorithms that predict hormonal misalignment from non-invasive wearable device signals. Solving these challenges is crucial to bring endocrinology into the era of personalised medicine. Having prime access to these datasets, and in addition to my skills and experience modelling hormonal dynamics, I am now in an ideal position to address these challenges. My long-term vision is digital endocrinology: personalised tools that support the prevention, diagnosis and management of endocrine conditions. This could take the form of an automated endocrine management system (e.g., a computer platform) for processing wearable and cortisol sensor data, smartphone interfaces, and automated drug delivery systems, for which we will require mathematical models and algorithms predicting dynamic adaptation to stressors. Ultimately, this interdisciplinary proposal will benefit patients, clinicians, and offer commercialisation opportunities, aligning well with UKRI’s strategic priority of transforming health, particularly toward remote (at home) healthcare applications that take advantage of mathematical and AI tools for wider societal benefit.

UKRI Gateway to Research · FY 2025 · 2025-11

NF2-related schwannomatosis (NF2-SWN) is a rare tumour predisposition syndrome characterised by multiple benign neoplasms within the central and peripheral nervous system and brain meninges. Bilateral vestibular schwannomas (VS), which form from abnormal Schwann cells lining the vestibulocochlear (sensory) nerves that transmit signals from the inner ear to the brain, are the hallmark of the syndrome. VS tumours in individuals with NF2-SWN are life-limiting, causing profound deafness, imbalance, difficulties in speech, mental health problems, and can lead to brain stem compression, hydrocephalus and death. Surgery, radiation and off-label use of Bevacizumab (a drug that blocks blood vessel development) are the only current treatments for NF2-SWN, all of which have significant side effects and have limited long-term effectiveness in many patients. Consequently, new treatments for NF2-SWN patients and VS tumours are urgently needed. The overall aim of this project is to provide a step-change in our understanding of the immune response to VS tumours, underpinning the development of new therapeutic approaches for NF2-SWN. VS tumours grow in a specific location within the cranium (outside of the brain tissue).  Due to their location, how they are recognised by the immune system and how tumour materials are able to drain from them into specialised immune tissues (lymph nodes), to activate tumour-specific immune responses, is unknown. Specifically, how VS tumours and tumour materials interact with recently identified vessels within the border regions of the brain (meningeal lymphatic vessels) to support development of anti-tumour immune responses has not been investigated. Moreover, whether these routes can be targeted to enhance immunity to VS tumours and suppress tumour growth and symptoms, is untested.  In Objective 1 of this project, we aim to fully define how VS tumours interface with cranial lymphatic vessel networks and cervical lymph nodes to coordinate anti-tumour immunity. There is growing evidence that VS tumours are comprised of various populations of tumour cells, immune cells and tissue (stromal) cells. In particular, we have discovered that although CD8+ T cells (immune cells that are meant to kill infected and neoplastic cells) are observed in human VS tumours, they exhibit a particular signature (phenotype), suggesting that they are dysfunctional and have lost protective tumour-killing ability. This indicates that approaches to reinvigorate CD8+ T cells, to enhance their neoplastic cell-killing capacity, may be effective at treating NF2-SWN VS tumours. Whilst such T cell targeted therapies have been highly effective in other tumours, they have not been explored in the context of NF2-SWN. In Objective 2 of this project we will dissect the compartmentalisation, identity and function of CD8+ T cells in VS tumours, and we will examine how targeting T cell activation and function can improve tumour control. Collectively, the work in this project will transform our understanding of NF2-SWN VS biology and will reveal new immune-based approaches to potentially treat VS tumours in patients with the NF2-SWN syndrome. Our results will be of significant interest to NF2-SWN patient groups and charities, such as NF2 Biosolutions, who we are partnered with and which supports extensive PPIE for our research. Our results will also have substantial impact for clinicians and pharmaceutical companies and may pave the way for compassionate (off-label) use and clinical trials of approved immune-targeted drugs for individuals with NF2-SWN.

UKRI Gateway to Research · FY 2025 · 2025-11

About 160 million years ago the common ancestor of therian (marsupials and eutherian) mammals left egg-laying behind and evolved a completely unique system for developing offspring. This new reproductive strategy involved the embryo implanting in the wall of the uterus, a step which is necessary for successful pregnancy in all mammals. The majority of mammal pregnancy loss occurs at this stage, and improving our understanding of the mechanisms involved will have significant impact in human fertility and reproduction and beyond, with livestock management, sustainable agriculture, and conservation efforts for extinction-risk mammals dependent upon successful implantation and pregnancy. Whilst all therian mammals share the requirement for implantation to occur correctly, there are differences between species in terms of precisely when this occurs (e.g. humans at around day 7 but in cows this process takes up to three weeks), what the position of the embryo is within the endometrium, and the morphology of the placenta that subsequently develops. In other words, there are parts of the implantation process that are conserved and there are likely some other parts that are unique to particular mammals. We want to gain molecular level understanding of what controls these similarities and differences in implantation strategy across mammals. Here, we are focussing on a group of small, yet very powerful, molecules called microRNAs that can control (in a dynamic and highly sensitive way) what proteins are made in a cell/organ. The primary mode of operation of microRNAs is to stop a specific target protein being made. There are thousands of known microRNA genes, some are shared between species and some are unique to species. MiRNAs are known to emerge at critical time points in the evolution of novel phenotypes in animals - implicating them in the evolution of novel phenotypes/morphologies e.g. the origin of implantation. We have already made significant progress to meet our goal e.g we know specific miRNAs that are key players in implantation, we know particular proteins that have changed their function at the origin of theria and are expressed in the uterus, we know what is controlling the expression of these miRNAs and we have predicted how the miRNA targets have changed across species. We have also developed the protocols, code, and technologies to enable us to carry out this work. Fortuitously major international efforts to provide genomic resources for large numbers of mammals have completed providing us with unprecedented power to compare patterns across ~240 eutherian mammal species. Dr Forde has used and developed specific types of technology (omics, in vitro models) to help address the question of how the uterine environment and the embryo interact with one another in a number of species including cattle and humans. Dr O'Connell's work has addressed how mammals are related to one another, how the functions of genes change through time and how genomes of species respond and adapt. This proposal marries these two areas of expertise with outstanding resources to address the fundamental question of how regulatory innovations impacted upon the origin and subsequent diversification of implantation strategies in mammals.

UKRI Gateway to Research · FY 2025 · 2025-11

There is a constant economic drive to make electronic devices smaller, and this miniaturisation has been achieved to date by fitting more transistor nodes onto smaller integrated circuits. This “top-down” approach is soon expected to hit a physical limit, and therefore alternative “bottom-up” approaches are now needed to meet this societal need in future. Single-molecule magnets (SMMs) have emerged as potential candidates to achieve high-density data storage and deliver smaller devices as they can show magnetic hysteresis, which is a memory effect. This property is at the molecular level rather than cohesive bulk magnetic interactions, as is the case for bulk magnets, allowing each SMM to store a bit of information; the energy required to flip magnetic memory in a molecule is much less than that needed to flip a magnetic domain. However, although SMMs have been known for over thirty years they have not yet been used in applied technologies. This is mainly a consequence of them currently only showing long-term magnetic memory using helium cooling, which is energy-demanding, unsustainable, and economically impractical to implement. In this project we will set methods for the routine synthesis of SMMs that operate above 100 Kelvin. This temperature is easily achieved with liquid nitrogen cooling (boiling point 77 Kelvin), which is cheaper and more sustainable than using helium cooling for achieving SMM technologies. Lanthanide SMMs, especially those containing dysprosium and terbium, have shown the greatest potential for high-temperature data storage to date. Highly axial dysprosium compounds with the metal coordinated by planar carbocyclic rings have previously shown magnetic hysteresis up to 80 Kelvin, due to a combination of the large magnetic anisotropy induced by this molecular geometry for these metal ions and the rigidity of the rings, but this approach has appeared to reach a plateau. Axial lanthanide compounds are challenging to isolate as lanthanides are large and show mainly ionic bonding regimes, thus additional molecules will tend to coordinate equatorially and introduce transverse fields, unless suitably bulky rings are used. We have recently discovered magnetic hysteresis above 90 Kelvin for a bent dysprosium compound bound by two nitrogen atoms and a pendant alkene. These preliminary results show a route to achieve the next step change in SMMs. Here we target formally two-coordinate lanthanide compounds with geometries closer to linearity, shorter metal-donor atom distances and more rigid coordination spheres. Ideal linear geometries will maximise the magnetic anisotropy and the purity of magnetic states, and higher molecular rigidity will reduce the effect of molecular vibrations that can be major contributors to magnetic relaxation. As the charge densities of single donor atoms can potentially be far higher than their more charge-diffuse carbocyclic ring counterparts, the target compounds can show greater anisotropy. This work will therefore deliver a new family of high-temperature SMMs with high effective energy barriers to magnetic reversal, and new record magnetic hysteresis temperatures. Once the target compounds have been synthesised, we will perform comprehensive physical and computational characterisation studies to define their electronic structures and SMM parameters. This will provide a deeper understanding of magnetic relaxation mechanisms and their relationship to molecular structure, allowing improved SMMs to be designed and targeted. We will also deposit the novel SMMs on surfaces, and we will characterise their magnetic behaviour in this environment; this is the necessary first step towards SMM devices.

UKRI Gateway to Research · FY 2025 · 2025-11

Collagen VI forms microfibrils that are important for providing mammalian tissues with their structure and mechanical strength by connecting cells with the surrounding extracellular matrix. Collagen VI is found in almost all tissues in the human body, for example the musculoskeletal system, skin, joints, lungs, eyes, kidneys and blood vessels. Unlike many other types of collagen, collagen VI does not have a typical fibrillar structure and organisation, instead it contains many globular domains and a short collagenous region, and forms microfibrils with a beads-on-a-string appearance. The importance of collagen VI in maintaining normal tissue function, is highlighted by mutations in collagen VI leading to muscular dystrophy and increased risk of cardiovascular disease. Moreover, a lack of collagen VI has been linked to osteoarthritis, and excessive collagen VI promotes fibrosis, inflammation and tumour growth. Although collagen VI is essential for maintaining normal tissue structure, its size and complexity have limited our understanding of its structure and the molecular details of how it assembles into microfibrils. The microfibril is assembled from three different collagen VI chains which form a heterotrimer, the basic building block of collagen VI, and four trimers come together to form the assembly unit of the microfibril. However, the molecular interactions that drive this assembly are not understood, which limits our understanding of collagen VI biology. Until recently, we had been unable to determine the structure of extracellular matrix fibrils due to their complexity, but advances in imaging are now enabling us to resolve these complex structures. Therefore, to support our proposal, we have recently determined the high-resolution structure of the bead region of the collagen VI microfibril using cryo-electron microscopy. This is the first high-resolution structure of any extracellular matrix fibrillar protein and our structure has revealed C-terminal regions that appear important for the formation of the microfibril. Therefore, in this project, we want to determine the molecular interactions that drive the different steps in collagen VI assembly. Using our mini-collagen VI expression system, we will use cryo-electron microscopy to image heterotrimers of different chain combinations and introduce mutations to test the requirements for chain selection and heterotrimerisation from different chains. Then we will determine the interactions underpinning the assembly of the collagen VI microfibril and image collagen VI microfibrils containing different chains. We will test our findings from these structures in cells, using endogenously tagged collagen VI to track assembly. Using this system, we will determine the consequences of disrupting specific interactions in collagen VI assembly, by introducing mutations designed to disrupt different assembly steps. As collagen VI microfibrils play a vital role in maintaining the normal structure of tissues, our research aligns with the “understanding the rules of life” BBSRC strategic priority. Understanding the molecular requirements for collagen VI microfibril assembly, which provide the mechanical properties of most mammalian tissues, could have significant health and economic benefits to the UK by providing valuable information towards novel tissue engineering strategies. Results from this study will not only be important for understanding collagen VI structure, but will also be of future interest to the pharmaceutical industry in developing therapeutics to modulate collagen VI deposition. As many human diseases are linked to excessive or insufficient collagen VI, our findings could provide new opportunities for future therapeutic intervention by selectively targeting collagen VI assembly or processing.  

UKRI Gateway to Research · FY 2025 · 2025-11

The NXCT is a centre of excellence delivering a service for UK users allowing them to exploit lab X-ray computed tomography for their research. We provide access to scanners and support the design of experiments, data acquisition and data analysis through our expert technical team. We also enable in situ and time-lapse experiment through our rigs and sample environments. We work across almost every sector from arts and humanities to medicine and life science but our main focus is on engineering and physical sciences where we work over all technology readiness levels (TRL’s). The NXCT is made up of a Hub at Manchester and lab facilities at Manchester, Southampton, UCL and Warwick universities with partnerships with Diamond Light source and Strathclyde and Swansea universities. In addition, we are providing training to develop the next generation of researchers who can exploit the power of X-ray imaging. Our outreach events and involvement in documentaries and public science is helping build the wider community. We are pushing the latest techniques in lab-based X-ray imaging to support cutting-edge experiments. Our aim is to support and develop the whole community where X-ray imaging can provide a distinct advantage providing a tangible economic, environmental and societal benefit. We work extensively with industry providing a bespoke service for SME’s through to large multinational companies. In our first 5 years of operation we have already supported over 1000 unique users with over 3500 days of beamtime and trained over 500 people. We have worked with over 100 companies and published over 180 papers. We will continue to build on our success and established processes to bring the NXCT and the UK to the forefront of lab X-ray CT research Worldwide. It is our vision to: Help users exploit the power of X-ray CT for their research Provide access to X-ray CT scanners, support experiment design and provide resources to analyse the data Develop new cutting-edge techniques in X-ray Imaging and analysis Promote X-ray CT and advocate the benefits of this technique to the UK research community Enable in situ experiments through support and provision of rigs available for lab and synchrotron experiments

UKRI Gateway to Research · FY 2025 · 2025-11

Immunotherapy has significantly improved survival outcomes for patients with cancer. Advanced therapies (ATs), including chimeric antigen receptor (CAR)-T, T-cell receptor (TCR-T) and tumour-infiltrating lymphocyte (TIL) therapies, have demonstrated promising results for haematological and solid malignancies. To date, eight cell therapies have received US FDA approval, with two CAR-T (leukaemia/lymphoma) NHS-funded. Despite this, barriers persist in wider use of ATs. Patients receiving CAR-T encounter significant concerns regarding accessibility/logistics and long-term safety. Contemporary post-approval experience with immune-checkpoint inhibitors highlights a research bias toward efficacy over safety, in part due to underfunding of mechanistic studies on immunotherapy-related adverse events. This has resulted in predominantly reactive versus preventative/proactive patient management strategies. Adverse events associated with T-cell-specific ATs are dominated by cytokine release syndrome (CRS), with up to 22% classified as severe, potentially requiring intensive care. Other serious clinical manifestations include immune effector cell-associated neurotoxicity syndrome (ICANS), haemophagocytic lymphohistiocytosis (HLH), and macrophage activation syndrome (MAS). Further complications e.g. coagulopathy, prolonged cytopenias and infections, can result in extended hospitalisation, psychological distress and significant caregiver burden. Despite these challenges, there is a lack of comprehensive guidance on long-term pharmacovigilance. Following consultation with expert patient and public voice partners (PPVPs) (ATMP Engage), we developed RISE, a multidisciplinary public-private consortium dedicated to facilitating safe and efficient clinical adoption of ATs. RISE leverages NHS and academic expertise within Manchester’s ecosystem, supported by four UK-based business partners (Poolbeg Pharma, Pfizer, Sanius, Randox) contributing >£2 million in cash and >£2 million 'in-kind', to integrate discovery science and translational research to enhance patient outcomes. RISE will employ scalable technology platforms to profile n=80-100 patients receiving standard-of-care CAR-T through a prospective observational clinical study. Concurrently, our main business partner Poolbeg Pharma will fund the translational endpoints of a Phase 1/2 trial (n=30-40 patients) investigating POLB001, a novel CRS-prevention agent. Leveraging MCRC Biobank and existing governance frameworks, we will collect and analyse longitudinal blood samples for high-dimensional immunoprofiling, bulk RNA-sequencing of PBMCs (including TCR/BCR repertoire analysis and T-cell fitness assessment), and point-of-care cytokine testing. Bone marrow spatial profiling and stool microbiome analysis will further elucidate toxicity mechanisms. Additionally, RISE will integrate expertise from the Manchester Wearables Research Group, Sanius, and The Christie Patient-Centred Research Team to develop tools for long-term safety monitoring. Wearables will provide continuous inpatient and post-discharge tracking, complemented by AT-specific patient-reported outcome measures (PROMs) for real-time toxicity assessment. Finally, we will work closely with experts from University of Manchester’s computational and data science teams, including Christabel Pankhurst Institute, to deliver on multimodal data integration. To compliment our strategy and robustness of key findings, we will employ artificial intelligence and machine learning approaches to create digital twins and virtual cohorts, simulating diverse hypothetical trajectories in patient outcomes. In summary, RISE represents an ambitious, interdisciplinary programme to improve AT safety and efficacy. Through cross-sector collaboration, technology integration and patient-centred approaches, we aim to establish new standards for AT development, regulation and implementation. Our long-term vision includes expanding RISE into a UK-wide network and serving as an exemplar blueprint for attracting further industry investment. With consortium members already actively engaged with ATTC, MHRA and NICE, we anticipate that RISE will further contribute to regulatory efforts and shape guidelines for safer AT deployment. We will establish an open-access toxicity database to support further research and collaborate with PPVPs to further build expertise in this evolving field.

UKRI Gateway to Research · FY 2025 · 2025-10

This 2-year collaborative project on Coptic manuscripts in the John Rylands Research Institute and Library (JRRIL) will bridge the existing divide between traditional academic research on these artefacts and the local Coptic church, offering a radically new approach by centering Manchester in terms of both the collection and the community. Over six hundred Coptic manuscripts sit in the JRRIL, which are significant for understanding the history of the Coptic Church and for studying the religious and social history of late antique and early Islamic Egypt. Despite their importance, these manuscripts have received limited attention, and their potential to connect scholarly research with local communities has not been fully realised. A pilot project brought together researchers at the University of Manchester and key figures in the UK Coptic community, revealing that manuscripts in the JRRIL can shed light on issues of special interest to British Copts: the formation and development of authoritative practices between the fifth and eleventh century. As manuscripts do not exist in isolation, it is also vital to investigate the history of the collection. The project has three objectives: To collaborate with the local Coptic Orthodox community to identify key manuscripts in the JRRIL that can illuminate the formative period of Coptic history, followed by detailed analysis of the selected manuscripts. To investigate the history of the Coptic archive at the JRRIL, situating it within the broader narrative of colonial-era collecting practices and their contemporary legacies. To raise awareness and access to the Coptic collection in Manchester, through collection encounters, a public conference, and a co-created digital exhibition and edited volume featuring critical editions, translations, articles, and reflections. The initiative brings together specialised skills in Coptic philology and manuscripts, knowledge of colonial archives, curatorial expertise, and people of Coptic heritage and faith living in or near Manchester today. The project’s outcomes have wide-ranging applications and benefits. Building on existing relationships with the local Coptic community, the project is committed to co-creation, connecting the Coptic community to their heritage. Creating a digital exhibition and digitising manuscripts promotes digital humanities, global access, and inclusivity. For academic specialists in Coptic studies, history, theology, and manuscript studies, the detailed study of manuscripts will provide valuable new data. By addressing the history of the archive, the project will contribute to broader discussions about decolonisation and the ethics of collecting and displaying cultural heritage. By focusing primarily on the Coptic manuscripts, this project decentres the usual focus on Greek and Latin to understand late antiquity. The dissemination outputs and events will enhance awareness of the JRRIL’s collection and heritage in the city of Manchester.

UKRI Gateway to Research · FY 2025 · 2025-10

The overarching aim of this workstream is to develop sustainable infrastructure and services which solve critical problems and thereby support digital innovation in (UK) mental health (services). Across key work packages, this digital workstream addresses the key challenges for digital mental health innovators relating to: alignment to users’ needs and priorities; market access; reimbursement; implementation; adoption; sustainable investment and scaling pathways. Our vision is to simplify and streamline the innovation pathway for digital mental health innovators and SMEs by reducing the onus on companies to navigate the complex landscape alone. We will bring clarity on reimbursement models for digital mental health, creating a step change in the opportunities for industry, de-risking plans to approach the UK market and providing greater confidence to investors. The redundancy in Information Governance and regulatory documentation that currently wastes NHS and industry resource will be alleviated by developing shared standards aligned to the aims of the NHS 10 Year Plan. Tried and tested guidance on deploying and scaling within NHS clinical settings will be developed alongside an expert centralised team of Digital Navigators for hands-on deployment support. A national consortium of innovation-ready Trusts and ICBs will be established to streamline adoption, de-risk investment, support multi-site pilots, and provide a single route for innovators to generate real-world evidence. Complementary blended funding models, global R&D partnerships, and big tech alliances will create new, scalable pathways to accelerate research, adoption, and commercialisation for UK-developed technologies. Finally, we will prototype a Mental Health Technology Observatory to surface NHS demand signals and provide a data-driven backbone to funding, policy, and adoption decisions, ensuring innovations are demand-led and systematically tracked across the ecosystem. The workstream will work closely with lived experience experts to shape and inform all key work packages in partnership with the MHG LEIP. An international advisory board comprising leading experts from international markets with deep experience in key domains including lived experience, reimbursement, regulation, implementation science, scaling and funding models will be developed to provide strategic guidance and real world insights throughout the programme. Everything in this workstream is designed to encourage industry and investment to flow into the UK by removing recognised barriers and streamlining approaches. Key challenges to industry are the lack of clear procurement, adoption and reimbursement pathways which we address as a priority. We will embed international learning through our expert advisory group, as well as engaging extensively with the real world experiences of digital mental health SMEs operating in the UK currently.

UKRI Gateway to Research · FY 2025 · 2025-09

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

UKRI Gateway to Research · FY 2025 · 2025-09

This grant supports IRIS Federation to deliver compute to its science activities by placing hardware at GridPP sites.

UKRI Gateway to Research · FY 2025 · 2025-09

Lysosomal storage disorders (LSDs) are a group of rare genetic diseases affecting children, for whom there are almost no treatment options. Genetic mutations cause problems in the lysosomes of cells, leading to neurological problems, cognitive decline and ultimately death. Some of these processes are similar to those found in Alzheimer’s Disease (AD) and children are often referred to as having paediatric AD. Therefore, understanding the processes in these diseases will have broad implications for neurodegenerative research. This project aims to address if the immune system may play a fundamental role in exacerbating neurodegeneration in LSDs. A major advance of the past decade is the understanding that immune system plays a fundamental role in brain function in health and disease. At the cutting-edge of this research is understanding how the brain's borders, which are hubs of immune activity, drive brain disease. The specific aims of this research are to: 1) Experimentally target the brain's borders, called the meninges, to improve brain function in a model of LSDs. 2) Test whether novel anti-inflammatory molecules can protect from ongoing brain damage in models of LSDs. 3) Investigate biomarkers of CNS disease progression and treatment efficacy in a rare cohort of patients participating in an open label Phase I-II clinical trial. The potential applications and benefits are both specific and broad. This research programme has the potential to reveal new targetable pathways, understand underlying neurodegenerative mechanisms (not limited to LSDs), provide novel biomarkers to assess treatment efficacy and, crucially, enable experimental treatments in patients either in future or current clinical trials.

UKRI Gateway to Research · FY 2025 · 2025-09

Chiral NanoGraphene for multifled Semiconductor Security - ChiNGS   This project aims to pioneer a new frontier in semiconductor device security by harnessing the power of chiral nanographenes—specially engineered, twisted carbon molecules with unique electronic and optical properties. While today’s hardware security often relies on complex software or circuit design, our approach seeks to embed protection into the very materials that form electronic devices, making them inherently resistant to tampering, counterfeiting, and hacking. Led by researchers at the University of Manchester, UK, in partnership with the University of Cologne, Germany, our collaborative team will design, synthesize, and test chiral nanographenes as advanced security elements. By integrating these molecules onto atomically thin platforms—such as graphene and hexagonal boron nitride—we aim to produce prototype devices whose electrical and optical “fingerprints” are impossible to clone or forge. These fingerprints can be used as physical unclonable functions (PUFs), providing robust means to verify authenticity and detect intrusion directly at the hardware level. Cutting-edge fabrication techniques, including thermal scanning probe lithography, will allow precise placement and manipulation of these molecules, while advanced characterization tools will assess their performance under real-world electronic conditions. This multidisciplinary effort will also facilitate training for young researchers, knowledge exchange across borders, and engagement with industry and the wider public through workshops and outreach. Our vision is to lay the scientific and technological foundation for a new generation of secure-by-design electronics—where materials science and device engineering converge to deliver tamper-proof, resilient hardware. The outcomes will not only deepen our understanding of chiral nanographenes and their remarkable properties but also open crucial pathways for enhancing national security, digital trust, and the safety of future digital infrastructure.