University of Sheffield

UKRI Gateway to Research · FY 2025 · 2025-12

About 1.41% of adults worldwide struggle with problematic gambling. These individuals often experience relationship breakdowns, financial difficulties, and mental health problems. Several psychological therapies are used to address problem gambling. However, treatment outcomes can vary widely, including up to 40% of people dropping out of therapy. Therefore, it is important to understand why some people engage and respond better to therapy than others. As with other mental health problems, understanding treatment predictors and moderators can help us do this. Treatment predictors and moderators Most treatment predictors are characteristics that someone has before starting treatment, which influence how well they do, no matter what treatment they have. For example, being female and being of a younger age have been identified as predictors of poorer gambling treatment outcomes. Other predictors (process predictors) are factors occurring after the treatment starts. For example, client-rated therapeutic alliance develops after the therapy has started, and predicts gambling outcomes. In contrast, moderators tell us which treatments work best for which people. For example, gamblers with low and moderate-to-high readiness to change attended either cognitive motivational behaviour therapy (CMBT) or Gamblers Anonymous (GA) meetings. The CMBT group reduced their gambling spending and frequency regardless of motivation level, but only those with a moderate-to-high motivation reduced their gambling in the GA group. Gaps in the Literature There have been only two systematic reviews specifically examining predictors of gambling treatment response. They found that male gender and lower depression scores were the most consistent predictors of successful treatment outcome. However, evidence was generally limited or inconsistent. Neither review identified process predictors, and neither included moderators of outcomes. Therefore, there is limited evidence supporting consistent predictors and moderators of treatment outcome and drop out in gambling. Random-effects and quality-effects meta-analyses are also limited in this field. Quality-effects meta-analyses allow us to determine the differences in outcomes that are due to study quality, thus yielding more meaningful findings.  Variances in study quality are likely to introduce bias and therefore impact meta-analysis results. A comparison between the two types of meta-analyses will be beneficial when evaluating the effect of treatment predictors and moderators on gambling outcomes. Clinical implications Identifying who is more or less likely to do well and remain in treatment is important for improving patient outcomes and reducing rates of relapse. It has the potential to inform the development of new and existing interventions for problem gambling, and to personalise treatment to the individual (e.g., adding modules for people who have additional mental health problems, or matching patients to therapists whose style suits them best). This could make treatment more effective and efficient. Aims of this review The proposed rapid evidence review aims to: 1.      Update the two previous systematic reviews by including evidence relating to predictors and moderators of gambling outcomes and drop-out at different time points (including patient, therapy, and therapist effects, where available). 2.      Conduct a random-effects meta-analysis to estimate how strongly predictors and moderators influence treatment outcomes. 3.      Conduct a quality effects meta-analysis to see whether accounting for the quality of studies impacts the results of the meta-analysis. This will help to identify good practice in delivering high-quality, reliable, and valid research.

UKRI Gateway to Research · FY 2025 · 2025-12

Adaptation to the environment is usually driven through natural selection, with those that survive and reproduce in greater numbers making a greater contribution to the next generation. The variation that is available for natural selection usually arises through random mutation in the genetic material passed between the generations. Whilst we know this process gave rise to the diversity of life we see today, useful mutations arise infrequently and so adaptation to environmental change can be slow. However, there are evolutionary processes that can bypass the protracted time required for adaptive evolution. Lateral gene transfer (LGT) can accelerate adaptive evolution by moving genetic information between organisms without sexual reproduction, effectively expanding the genetic substrate that natural selection can act upon. This process is known to be ubiquitous in bacteria, where it can spread traits such as antibiotic resistance. However, over the last decade a number of examples have been identified in plants and animals, where it can drive environmental adaptation. LGT between different grass species is widespread in natural grasslands. However, beyond its documented occurrence, we know almost nothing about how these transfers happen or how commonly they occur. For this project, we will use grasses as a model system to address these unanswered questions, with three main objectives: Objective 1: Test if reproductive contamination underpins grass-to-grass LGT. We hypothesise that reproductive contamination (the introduction of DNA from a third party during sexual reproduction) is how genes are moving between reproductively isolated species in the wild. Objective 2: Quantify the background rate of LGT in a natural grassland. The background rate of LGT is what ultimately generates the substrate that selection can act upon, and its estimation is essential to determine the relative contribution of LGT to adaptive evolution. Objective 3: Test if LGTs are inserted non-randomly into the recipient's genome. For LGT to be successful, the third party DNA needs to be incorporated into the recipient's genome in a location where it can persist and influence adaptive evolution. This work will reframe our understanding of the importance of LGT in plant evolution, providing a plausible pathway by which “natural genetic engineering” can enable species to expand their genepool to incorporate novel genetic variation and fuel environmental adaptation.

UKRI Gateway to Research · FY 2025 · 2025-12

Feeding the growing global population will require an increase in total food production of around 50% by 2050. Though yields of our major crops are increasing, current annual yield increases are insufficient to meet this demand. To produce enough food, we need to improve crop productivity, producing greater yields on a per-area basis. At the same time, the climate crisis brings unprecedented challenges for crop production, with adverse environmental conditions such as heat waves decimating harvests. We need crops that are more productive, whilst also being more resilient and yielding well under hostile environments. My research addresses these pressing needs to boost productivity and heat resilience by exploring the overlooked contribution of crop reproductive physiology. The flowers and grains of cereal plants, such as rice and wheat, are surrounded by specialised modified leaves called bracts. These bracts can help to cool the vulnerable flowers by evaporative cooling through microscopic pores called stomata. In leaves, by controlling gas exchange between the plant and its environment, stomata determine the rates of carbon dioxide uptake for photosynthesis, and also water vapour release for cooling. Bracts also photosynthesise, producing extra sugars to fill the grains, and in wheat we know that this can contribute 12-42% of total grain yields. The function of bracts and their stomata offers untapped potential for yield gains and protective cooling of the vulnerable flowers and developing grains. In this project I will explore the function of bract stomata in wheat to reveal this potential. Then, this knowledge can be transferred into rice. Unlike wheat, rice lacks outward-facing stomata on its bracts and has much lower rates of floral organ photosynthesis, suggesting an even higher yield gain potential. The project is divided into three core objectives, with high value deliverables. Objective 1 explores the function of wheat spike stomata in photosynthesis and cooling. By characterising the physiological consequences of different bract stomatal densities, in heat stressed and controlled field grown conditions, we can determine their contribution to crop yield. Lab work will also demonstrate the functional characteristics of these stomata. Objective 2 will determine how bract stomatal distributions are determined. Uncovering the gene regulatory networks that control bract stomatal development in wheat and rice will allow us to understand why their stomatal distributions differ and offer targets for further manipulations. Objective 3 will involve manipulating rice stomatal distributions to enhance panicle cooling and photosynthesis. Transferring targets from Objective 2 into rice will allow us to optimise stomatal distributions in this core crop and verify their effect on photosynthesis, cooling and yield to engineer crops for the coming climate crisis. With a rapidly increasing population, and a climate crisis endangering the global food supply, generating climate ready crops is essential. This project will offer new breeding targets for two of our core crops, wheat and rice, to allow us to increase yield by optimising bract photosynthesis. Furthermore, precision manipulations to bract stomatal distribution have the potential to protect flowers from high temperatures that devastate crop yields, increasing stress resilience.

UKRI Gateway to Research · FY 2025 · 2025-12

Generative AI is now used by hundreds of millions of people worldwide. In the United States alone, 18% of adults have used ChatGPT. As the fluency and affordability of generative AI continue to grow, so does its wide-ranging misuse in cheap, but highly convincing large-scale disinformation campaigns. For example, NewsGuard has identified close to 800 AI-generated news and information sites, which operate with little human input and are propagating false narratives. Therefore new research is urgently needed to better understand how new AI models can be misused for the generation of false narratives in multiple languages and formats. To counter AI-generated disinformation in the wild, novel more effective, multilingual AI models for disinformation detection are also urgently needed. To this end, we will leverage on the two teams’ world leading research in Natural Language Processing (NLP), Machine Learning, and mis/disinformation detection. Thus this project will also strengthen the capacity of both UK and US in the key growth areas of NLP with machine learning methods and practical applications of AI. To accomplish this vision, the following objectives will be addressed: O1 GENERATE: Investigate different ways of bypassing the safeguards of Large Language Models (LLMs) to generate disinformation in multiple high/medium- and low-resource languages and formats (including news articles, social media content, and blog posts). We will leverage translation, paraphrasing, and perturbation methods with prefix-style prompts to create a total of 12 snapshots (quarterly across 3 years) of LLM-generated disinformation in 9 languages, 5 formats, and using multiple evolving state-of-the-art LLMs per snapshot. O2 DETECT: We will start by studying the ability of citizens, journalists, and fact-checkers to distinguish AI-generated disinformation from human-authored disinformation and true news. Next we will use these insights to develop novel multilingual LLM-based models for accurately detecting human-written and LLM-generated disinformation, taking into account the effects of multilinguality, text length, domain/topical diversity, and the different AI generators themselves. O3 INTEGRATE & VALIDATE: Test the real-world application of the detection models from O2 by integrating them within Agence France Presse (AFP)’s open source content verification browser plugin, currently used by over 100,000 professionals worldwide.  Validation activities will involve all our fact-checking partners listed below. O4 IMPACT: Impact activities will target fact-checking and media organisations, policymakers, social media platforms, law enforcement agencies, and academics. Training and capacity building activities are aimed at academic beneficiaries, including students, early career researchers, and academics from social sciences and computer science. The outcome from O1, O2, and O3 will be an open-source benchmark dataset and novel methods for analysing AI-generated disinformation, useful both for the research and professional communities. O2 will also help improve our understanding of human capacity to unearth AI-generated disinformation, and help design better fact-checking and content verification tools in O3. For reproducibility, the codebase and models from O2 will be made available to vetted researchers, to prevent AI misuse by disinformation actors. The plugin integration code in O3 will be provided as a branch on AFP’s github repository. O4 will produce numerous peer-reviewed publications in top AI venues, across the UK and US teams, as well as online training materials, a summer school, and a policy-oriented white paper. The teams will ensure broader impact through their collaboration partners in Europe (FullFact, AFP, Deutsche Welle, the Journal, EDMO, FuJo, GLOBSEC, ATC) and worldwide (IFCN, SNUfactcheck, Washington Post).

UKRI Gateway to Research · FY 2025 · 2025-12

This is a project about belonging: to a family, to a nation, and to a generation shaped by war. Over 1.2 million African soldiers fought for Britain and France during the Second World War (WWII) while their families survived the instabilities of colonial rule. War temporarily expanded the boundaries of national belonging, as Britain and France depended on and celebrated colonial soldiers. Wartime violence and trauma continued into peacetime, as African soldiers were returned to family life under racial hierarchies. It is unsurprising that questions of citizenship and national belonging surfaced in 1945 and remain vitally important today. Examining how African soldiers experienced their integration home after WWII enables us to understand the connection between government treatment of veterans, celebration and commemoration of conflict, and feelings of national belonging among marginalised and racialised communities. This project will, for the first time, examine the comparative ways men, women and their families from Zambia, Senegal, South Africa and Congo-Brazzaville rebuilt their lives and created new independent nations after the trauma of WWII. Its timespan of 1945-60 shows how boundaries of post conflict trauma move between family circles and larger societal arenas, impacting on national and transnational issues. By concentrating on ex-servicemen as political agents, colonial rulers (and some scholars) have assumed that political engagement was male-dominated, an assertion this project challenges. By focusing on home-coming, this project draws women and families into the frame of analysis, asking how global and domestic contexts affected the reintegration of ex-servicemen into their civilian lives; and interrogating how gender shaped the connections between war and independence movements that flourished between 1945-60. This historical approach is vitally important to understanding processes of decolonisation and how legacies, continuities and reiterations of inequalities in post-colonial Africa and Europe impacted feelings of national belonging. With support from the Imperial War Museums and non-academic partners we will: create opportunities for international collaboration; diversify our our understandings of WWII creating stronger feelings of national belonging; improve understanding of the mental health needs of Black veterans and their families; use this research to influence policy; engage with local Black and African artists; create resources for schools; and draw new audiences to heritage collections. At a time when British and French nationalism are contentious and divisive issues, this project seeks to present an alternate way for people to connect with their heritage and nationality, reflecting truly global and multicultural nations. Better understanding of war trauma will lead to better mental health provision for current veterans and their families, often from or serving in former colonial territories. This Future Leaders Fellowship (FLF) will transform the academic landscape on veteran and war studies, gender and imperial history, and medical humanities while achieving the long-term goal of ‘decolonising’ popular histories of WWII; engaging critically in debates on race, integration, Black Lives Matter, systemic racism and islamophobia currently taking place in France and Britain; and thus contributing to the process of becoming genuinely postcolonial nations.

UKRI Gateway to Research · FY 2025 · 2025-11

Quantum technologies (QTs) have the potential to revolutionise fields like computing, communication, and sensing by leveraging the unique properties of quantum dynamics, enabling information processing beyond classical devices. However, precise control over these fragile quantum systems presents a significant challenge to realising QTs. Even in idealised, isolated systems, rapidly changing the system induces undesirable transitions, disrupting the control protocol and introduces errors. This creates a fundamental trade-off: faster operations increase the likelihood of errors, while slower operations, though more reliable, are impractical for real-world applications. The challenge becomes even more complex in practical quantum devices, which are never fully isolated from their surroundings and are often significantly impacted by environmental fluctuations. These environmental interactions, such as those between a system’s electronic degrees of freedom and the vibrational modes of the surrounding material, lead to decoherence and dissipation which, in-effect, erases quantum phenomena necessary for QTs, thereby degrading the performance of a device. Solid-state quantum devices, for instance, face significant challenges in maintaining a quantum state under these conditions, limiting their scalability. Therefore, to ensure reliable operation, accounting for these environmental influences is essential when designing control protocols for real-world quantum systems. This is particularly challenging, as the complexity of environmental interactions often prevents their effects from being accurately captured using conventional methods which assume weak environmental coupling., This project seeks to overcome these challenges by integrating cutting-edge methods from open quantum systems theory with machine learning tools. Open quantum systems theory allows us to model the interactions between quantum systems and their environment, providing insights into how these interactions degrade performance. Central to our approach is integrating tensor network methods—efficient numerical techniques for simulating quantum systems with strong environmental coupling—with machine learning tools, such as Bayesian neural networks. This hybrid framework will enable the design of optimal control protocols for complex systems, significantly reducing computation time compared to traditional methods. Ultimately, this project aims to develop control strategies that effectively counteract environmental interactions while enhancing the speed of quantum operations. A key focus will be on developing Shortcuts to Adiabaticity (STA) for open quantum systems strongly coupled to their environment. In isolated systems, STA protocols cancel the unwanted transitions that occur when control fields are applied rapidly, reducing the trade-off between fast quantum control and the accumulation of errors. However, developing such protocols for strongly coupled open systems remains an open challenge. The theoretical framework developed in this project provides a novel approach to addressing this challenge with implications for solid-state QTs, such as quantum dots and defect centres in crystaline materials. By collaborating with experimental partners, the developed methods will account for real-world constraints and complexities in experimental setups, ensuring the practicality of the resulting protocols. This project will provide a flexible theoretical framework capable of addressing key challenges in the control of realistic quantum systems. The aim is to make QTs more robust and scalable, bringing us closer to their widespread application in various industries, from secure communication to computation, helping to drive the next generation of technological innovation.

UKRI Gateway to Research · FY 2025 · 2025-11

Sustainable bioprocessing for commodity chemicals/materials faces several challenges to be economically competitive with those petroleum-derived.  Feedstocks used for fermentation are typically sugary materials which could be used for foodstuffs.   Hence, gas fermentation, which uses waste gases, is a promising approach.  Conventional downstream separations in bioprocessing are appropriate for high value added bioproducts, such as biopharmaceuticals and nutraceuticals.  But these methods are too expensive for low value added commodity chemicals and materials. In BIOMPOLY, we propose microbubble mediated methodologies to enhance gas fermentation for faster metabolism, and then microbubble mediated downstream separation schemes, both aimed at reducing costs.   The exemplar gas fermentation is to produce a bioplastic, polyhydroxybutyrate (PHB), which is one of a class of polyhydroxyyalkanoates (PHAs) that are biodegradable in all environments, including seawater.   Although only ~100 kilotonnes annually are produced, PHAs have the potential to replace up to 90% of fossil polymers.  Global PHB Production Market Value was $102 million in 2021 and is expected to be worth $283.5 million by 2028. A CAGR of 18.5% is set to grow heavily in the EU due to bans on single-use plastics. Conventional gas fermentation must take special care as the two major nutrient gases, methane and air, are potentially flammable in the headspace of the fermenter.  Separate microbubble dispersions of methane-rich waste gases and of air can be designed and controlled so that one of the gases is outside the flammability limits, as the microbubble size can be controlled to be non-buoyant, so all the nutrient gas is used in the fermenter. Conventional downstream PHA extraction and purification is energy-intensive and involves the use of hazardous chemicals and solvents such as chloroform, dichloromethane, or a combination of solvents.  Our methodologies use gentle, microbubble mediated cell lysis, so as not to damage the PHB nodules, with selective flotation by tuning microbubble sizes to harvest the cells and then separate the PHB from the remaining biomass. BIOMPOLY will involve two types of engineering biology from the unique UK laboratory producing methanotrophs (methane and potentially CO2 consuming bacteria) that generate PHBs currently.  The methanotroph strain will be genetically engineered to maximize the yield, increase the growth rate, and stop the PHB from being consumed by the bacterial host.   Secondly, we will symbiotically engineer a co-culture of microalgae with the methanotroph strain, to consume the CO2 produced by the methanotroph, and produce oxygen for the methanotroph.   Both approaches aim to match microbubble size distribution to the size distribution of the microbes, so that complexes of microbes and microbubbles will be formed, called Desai artificial lichen (DAL).  DALs exploit the gas exchange across the microbubble, which is orders of magnitude faster than dissolving the practically insoluble nutrient gases like methane, in the fermentation media.  From observations in the literature, some DAL complexed microbial consortia have much faster coupled metabolisms than those without the local gas exchange.  By matching the microbubble/microbe size distributions, we aim to optimize the formation of such complexes.  The co-culture will have the benefit of not needing to introduce air microbubbles, so an intrinsically safe design. Techno-economic and sustainability assessment of the potential upscaled BIOMPOLY will be undertaken -- necessary to allow decision makers to determine likely commercial feasibility so that an impact plan can be developed.

UKRI Gateway to Research · FY 2025 · 2025-11

Context The average age of water supply pipes in the UK is around 80 years and their length is ~350,000km. We have no idea of the condition of this infrastructure. Buried pipes continue to lose water at 2,924M litres every day. The majority of water loss is through so-called hidden or background leaks which are impossible to detect through the existing sensor network and signal analysis. The UK Water sector has committed to triple the rate of sector-wide leakage reduction by 2030 and half leakage by 2050 but lacks technology to reliably detect these leaks and onset of critical changes that lead to water losses. In response to this we propose to develop new biologically-inspired miniature devices called neuromasts that are incredibly sensitive and capable of detecting hidden leaks and damage leading to failures. We will integrate these devices with autonomous robots to make searching for leaks pervasive and in real time. This idea is inspired by sensing mechanisms found in aquatic animals. It will require a new theoretical basis to revolutionise the way buried water supply pipes are inspected and rehabilitated. The challenge the project addresses There is a lack of science to explain: (i) how to make the bio-inspired sensors to measure mathematical quantities that are rarely measured; (ii) how to interpret signals from bio-inspired sensors;  (iii) how to deploy these sensors to maximise the probability of pipe failure detection and to minimise the effect of the sensor's shape; (iv) how to use this technology to make pipes failure-free. Aims and objectives The aim is to develop a world lead in acoustic sensing for condition detection of buried water supply pipes. The objectives are: To develop a new theory for the behaviour of high-order acoustic pressure derivatives in waveguides with imperfections.  To develop new micro-electromechanical sensors (MEMS) to measure high-order acoustic pressure derivatives.  To deploy the new sensors on board a robot, configured for measurements in water in a pipe; to validate the new theory and the implementations via experiments and simulations.  To engage with end users to iteratively develop and demonstrate the benefits of the new science and technology.  Potential applications and benefits This work is timely. Despite considerable investment from both government and industry to improve traditional technologies for inspecting buried water pipes, these technologies continue to require significant human intervention. They work over a relatively short pipe length, limited resolution, are specific to the wall materials and are usually static or relatively slow to meet the future challenges, e.g. pipe network resilience, zero-failures, ‘No Dig’ and climate change. None of them is bio-inspired or supported by crafted sensor technologies. The need for a radical new solution is reflected in the message from major end-users that bio-inspired sensors delivered by smart robots are the future of inspection of their buried pipe infrastructure. This is a main application of the science and technology this project proposes to develop. This solution can be deployed dynamically and pervasively in the buried pipes supporting the UK’s water industry initiative for zero failures and ‘No Dig’. Originally intended for clean water and pressurised wastewater pipes, these sensors can be adapted to work in other pipes, e.g. petrochemical and nuclear. A number of industrial foundries are well placed to develop the new sensor technology into a successful product to be marketed globally.

UKRI Gateway to Research · FY 2025 · 2025-11

Context Understanding the impact of global increases in atmospheric CO2 concentration [CO2] on crops is a key global research objective. Research over the last 10 years has revealed that, while there can be beneficial effects on yield, there are also trade-offs in terms of negative impacts on plant-water relations, nutrient uptake and leaf temperature. This is largely due to elevated [CO2]-induced reductions in stomatal aperture. These play out as reductions in evapotranspiration, which result in warmer leaves and reduced water and nutrient uptake from the soil. Accordingly, understanding the cellular mechanisms that allow stomata to respond to elevated [CO2] is vital for mitigating the negative effects of climate change on food production and nutrient content. Recently (unpublished) we have found that a long non-coding RNA (lncRNA) has a major role to play in the response of stomata and other cells in the leaf to increasing [CO2]. Our discovery is a completely novel and unexpected insight into plant CO2 responses and as such represents a potential step-change in our understanding. It opens up a totally new avenue of research investigation into the regulation of CO2 driven processes. The challenge LncRNAs are important regulators of gene expression in animals and plants. Unlike protein coding genes, lncRNAs do not usually encode for functional proteins. Instead, they regulate the expression of protein encoding genes. In Arabidopsis we have identified a lncRNA locus that we named Regulator of Stomatal CO2 sensitivity (LRSC1), whose transcripts are extremely highly enriched in guard cells compared with other leaf cell types and that has homologues in other members of the Brassicaceae. lrsc1 mutants consistently display significantly increased evapotranspiration, suggesting that the mutants’ guard cells are less sensitive to CO2. Remarkably, given the guard cell enrichment of the lncRNA transcripts, changes in whole leaf gene expression in response to increased [CO2] are also virtually eliminated in the mutant. Our challenge now is to understand the mechanism by which LRSC1 regulates plant responses to increasing [CO2]. Aim: To understand how LRSC1 regulates plant responses to CO2. To achieve this aim, we will address three objectives: 1) Determine the molecular mechanism of action of LRSC1. 2) Establish how LRSC1 regulates sensitivity to CO2. 3) Determine conserved functions of LRSC1 across the Brassicaceae.   Potential applications and benefits In 2023, the UK Brassica and field vegetable market was worth £1.5 billion. Determining how LRSC1 regulates stomatal and leaf sensitivity to [CO2] will allow us to manipulate crop water use, nutrient, uptake and cooling in economically relevant Brassica species. More widely, we critically lack knowledge of cell-type specific responses to CO2. This project will identify CO2 responsive genes in different types of leaf cells, which may provide novel targets for engineering more productive crops that are resilient to increasing global CO2 levels. Relevance to BBSRC priorities Rising [CO2] and associated global warming is already having major impacts on crop productivity. Our research aligns with the BBSRC strategic delivery plan for sustainable agriculture and food and also addresses fundamental questions focused on understanding the rules of life.

UKRI Gateway to Research · FY 2025 · 2025-11

People spend most of their lives in a variety of indoor environments. This occurs principally in homes, but also in schools, workplaces, and health and care environments. Scientists, practitioners and the public are increasingly aware of the impact of poor quality buildings on health and wellbeing, as emphasized in the last few years with the tragic death of Awaab Ishak from indoor mold and the role of ventilation design in the spread of SARS-CoV-2. Poor outdoor air quality from PM2.5, NO2, and ozone exposures was estimated to contribute to 17,000 premature deaths and 345,000 Disability Adjusted Life Years lost in 2021 in the UK, making it the single most important environmental contributor to the burden of disease. However, there is much we still do not understand about indoor air quality. We cannot simply transfer our understanding from outside air research to the complex indoor environment - both the composition of pollutants and the airflows that carry them are vastly different, creating a complex set of exposures we do not yet understand. The drive to net-zero provides substantial opportunities for building and retrofitting buildings to make them healthier as well as energy efficient. Yet, this also poses substantial risks for increasing poor building quality, and reducing air exchange and dilution of pollutants. Further, it is well understood that a focus on the performance of an engineered system without considering the role of the users leads to underperforming systems. This has been well demonstrated in buildings where ventilation systems are often not used appropriately, are ill maintained, and are sometimes even switched off and covered up, all resulting in a buildup of pollutants and often a reduction in air quality post retrofit. Through this network we intend to tackle the challenge of creating healthier indoor air for everyone, including a focus on the most vulnerable. We will achieve this we will create collaborations and co-design research projects around the question “How much and what is in PM2.5 indoors, what are its health impacts, and what are the most effective and equitable ways to reduce those impacts?”. Specific network activities will include: Co-creating feasibility studies and research proposals with members of the public, particularly those sensitive to the effects of poor indoor air quality. Developing collaborations between a range of health expert, engineers and indoor air scientists to inspire novel approaches to assess health implications of poor indoor air quality by making better use of the existing UK birth cohorts. Working with industry to understand current and near future technologies for delivering healthy indoor environments and the industrial perspective of the related research needs. Exploring sampling methods to better understand the constituents of PM5. Both using static samplers and personal samplers to capture variations in exposure as an individual travels through a range of engineered environments that they encounter in their daily life. Exploring the ethical implications of personal air quality sampling with academics and members of the public to develop research protocols that acquire useful and robust datasets while respecting a participants privacy and ensuring ethically sound research. Engaging with a wide academic audience through a mix of online and in person events. In particular developing the future research capacity of the UK by providing specific early career training and support to apply to our feasibility fund.  

UKRI Gateway to Research · FY 2025 · 2025-11

An enormous amount of fluids — from water to oil and natural gas — is transported across the globe through pipes and ducts. In the United Kingdom alone there is over 215,277 miles of water pipelines, enough to travel the circumference of the world 8 times. Most often these flows are turbulent, and the associated frictional losses are much larger than those of laminar flows, making it a far less energy-efficient way of transporting fluids. According to estimates, around 10% of the global electric power consumption is spent by pumping systems to overcome frictional drag in pipelines,  including not only large-scale oil/gas pipelines, but also domestic networks. Fighting against climate change, the most desirable, yet challenging, outcome that a flow control method could achieve is to completely extinguish turbulence, hence zeroing the associated frictional losses. Even when relaminarisation has been achieved in lab experiments and numerical simulations, it was not possible to explain on a theoretical basis why the control strategy worked, and under which conditions. This lack of understanding has so far prevented up-scaling of relaminarising control strategies for deployment and implementation in practical engineering systems. To overcome these limitations, this project will exploit recent advances in machine-learning and data-driven methods to unravel the physical mechanisms underlying the phenomenon of forced relaminarisation and to provide a mathematical description of its dynamics through the theory of dynamical systems. The understanding gained in this way will be leveraged to develop novel control strategies, based on the same principle, to completely suppress turbulence in pipeline flows of industrial interest. Such vision has important societal and economic implications because vanishing turbulence will massively curb carbon emissions, thus leading to improved air quality and contributing to meeting the net-zero-by-2050 target. This achievement is also of great fundamental interest as it would provide a better understanding of the universal mechanisms sustaining wall-bounded turbulence. As this knowledge applies not only to pipelines but to many other flows of industrial relevance (e.g. flows over the wing of an aeroplane or a turbine blade), it will enable us to control and improve e?iciency of these systems in a variety  of engineering and technological applications.

UKRI Gateway to Research · FY 2025 · 2025-11

This project addresses the urgent challenge of climate change by exploring land-based carbon dioxide removal (CDR) strategies, such as afforestation/reforestation, wetland restoration, and enhanced rock weathering (applying crushed basalt rocks to soils to accelerate natural carbon capture). While these methods hold great promise for reducing atmospheric carbon and mitigating climate change, their broader impacts on air quality, ecosystems, and the climate itself remain poorly understood. These knowledge gaps limit their effective and sustainable implementation. Building on findings from the first phase of my UKRI Future Leaders Fellowship, this research will investigate how natural events, like wildfires, and human-driven factors, such as air pollution, influence the effectiveness and durability of land-based CDR strategies. For example, my initial work has shown that atmospheric chemistry and albedo feedbacks (ie, changes in how surfaces reflect sunlight) can reduce the cooling benefits of tree planting by up to 30%. This underscores the need for a deeper understanding of the trade-offs, synergies, and unintended consequences associated with these strategies. The project has three main objectives. First, it will evaluate how disturbances, such as wildfires and air pollution, impact the carbon storage potential of afforestation/reforestation strategies under future climate scenarios. Second, it will assess the effectiveness of combining different land-based CDR strategies, such as enhanced rock weathering with afforestation/reforestation, and bioenergy crops, identifying ways to maximize benefits while minimizing trade-offs. Third, it will focus on land-use strategies specific to the UK, providing detailed assessments of their air quality and climate impacts and their contributions to achieving the country’s Net Zero targets. This project will fundamentally advance the science of land-based CDR strategies by addressing these complex and interconnected questions, providing actionable, science-based recommendations for policymakers and practitioners. For the UK, the findings will support Clean Air Strategies, sustainable land management, and Net Zero commitments. Globally, the research will inform upcoming Intergovernmental Panel on Climate Change (IPCC) assessments and guide international climate negotiations, including the United Nations Framework Convention on Climate Change COP meetings. Collaborations with leading organizations such as the National Center for Atmospheric Research (NCAR), WWF, and DESNZ will ensure the research is grounded in real-world challenges and directly applicable to policy and practice. Partnerships with industry, including UNDO and the Future Forest Company, will translate findings into scalable solutions for land-based carbon removal, bridging science, policy, and implementation. An essential aspect of this fellowship is training the next generation of Earth scientists. The project will provide early-career researchers with opportunities to develop expertise in advanced Earth system modelling, big data analysis, and interdisciplinary collaboration. Through professional development programs and partnerships with leading institutions, team members will gain critical skills to integrate science with policy and practice, equipping them to tackle the global challenges of climate change and air quality.

UKRI Gateway to Research · FY 2025 · 2025-10

The rise of Artificial Intelligence (AI) has evoked a transformative journey in many disciplines of science, technology, engineering, manufacturing, medicine, and art, promising unlimited possibilities for innovation, efficiency and creativity. In the field of architecture, the growing interest in AI-empowered tools, such as Midjourney and DALL-E, have sparked new lines of enquiry into disruptive architectural design technologies and methods: they herald the revolution of contemporary practices to come and contribute significantly to (re)shape our built environment. This project aims to delve into the burgeoning realm of generative AI (GAI) in architecture and focus on GAI for transforming architectural practice through innovative Building Information Modelling (BIM) processes. The advent of GAI in architecture marks a shift towards more integrated, adaptive, and sustainable design processes, but more work is still needed to ensure a seamless integration of GAI. A significant gap exists between the technological capabilities of GAI and its practical implementation with inter-connected, domain-specific BIM models in everyday architectural practice. The proprietary nature of individual building projects limits public access to BIM data for direct AI use. Existing AI applications with BIM are often task-driven projects with bespoke software development. Therefore, the broader use of GAI with natural language prompts would require further development with BIM to fully understand the extent to which GAI technologies can support the transformation of the built environment. Wang has investigated AI-enabled technologies to be integrated with building information modelling (BIM) processes in contemporary Architecture practice. The central inquiry revolves around understanding how AI can boost efficiency and creativity in BIM processes within practices, ultimately impacting sustainability and innovation in built environments. Wang's recent work on automating room classification using 2D images was to reduce labour-intensive modelling processes for easy-access building performance evaluation (BPE) in early residential building planning (Zhao et al., 2022). Another example investigated a streamlined parametric modelling workflow to automate daylight glare assessments for the Chinese green building standard (Wang et al., 2022) and afford optimised design solutions, rendering opportunities to address intricate architectural challenges with unprecedented precision and creativity. Research conducted in this secondment aims to bridge the gap between the theoretical potential of GAI and its practical implementation in architecture. By examining the current state of GAI use in architectural practices, the project will identify key challenges that hinder its widespread adoption, such as technical limitations, knowledge gaps, and resistance to change. Furthermore, this project will explore the ethical considerations and implications of AI-generated designs, ensuring that the GAI integration with BIM upholds the creative integrity of the architectural profession. In this project, Hawkins\Brown (HB), one of the leading Architecture firms investigating future affordable, inclusive, sustainable built environments, will host the secondee (Wang) to co-develop a deployable GAI for BIM toolkit for the broader architecture, engineering, and construction (AEC) industry uptake. The outcomes from this secondment will alleviate the stress and anxiety of inundating GAI tools and boost the confidence of stakeholders in leveraging GAI for enhanced efficiency and creativity across various stages in architecture design and construction. With the prowess to analyse vast datasets, GAI is envisaged to drive the architecture revolution forward, from streamlining BIM processes to fostering innovative design ideas that respond to ever-evolving environmental and societal demands.

UKRI Gateway to Research · FY 2025 · 2025-10

Located at the Eastern edge of the Venetian Empire and the Western edge of the Ottoman Empire, early modern Crete and Cyprus have been at the periphery of musicology. As spaces of coloniality and shifting hegemonies, shared by acoustic communities with very different histories, this area has been ill-served by traditional methods. Sources amenable to philological and archival research are scarce, and a paradigm built around composers and institutions has so far failed to capture the lived historical realities of a complex intercultural situation. SONICC investigates long-standing processes of friction and hybridisation based on different sounds, noises, musical practices and languages, that affected local Greek, Ottoman, Jewish, Armenian, Arab and Italian populations. The project will approach this complex topic via two strands of methodological innovation. First, drawing on the emerging fields of Sound Studies and Auditory History to address sound as a distinct historical category with a key role in identity formation, using state-of-the art critical approaches to investigate Mediterranean sonic identities through decolonial and global history perspectives. Second, an intermedial approach investigating literary, visual, material and architectural materials as sources for the history of sounds and musics, as well as archival and notated music sources. Dr Hatzikiriakos has a strong track record in the study of musical identities, and is skilled with primary sources in Italian, Greek and Latin. At Sheffield, he will work with Prof Tim Shephard, a prominent authority on early modern musical identities and visual and material sources in musicology; and Dr Erin Maglaque, a leading expert on Venetian colonies. Secondments at the Orient-Institut Istanbul and the University of Athens will meet training and research needs. The MSCA will establish Dr Hatzikiriakos as an independent voice advancing global and decolonial approaches to early modern musical identities.

UKRI Gateway to Research · FY 2025 · 2025-10

Project Dates: (15 September 2025-14 December 2027) Elizabeth Bishop (1911-1979) is one of the twentieth-century’s most important and influential poets. Yet few of the hundreds of postcards she sent during a lifetime of peripatetic travel, or her photographs, slides, and other art works, have been exhibited or published. Our project argues that these hitherto unseen visual works profoundly influenced Bishop’s poetry: looking at them transforms our understanding of Bishop’s art and methodological approaches to modern poetry more generally. In 2023, as part of an innovative pilot study, I co-curated the first exhibition of Bishop’s picture postcards at Vassar College, USA, with my PcL, Susan Rosenbaum. The exhibition was composed of fifty-five Bishop postcards from Vassar’s collection, with an exhibition catalogue and online version of the exhibition at Vassar. The exhibition attracted widespread media attention, featuring in The New York Review of Books, The Paris Review, and The Times Literary Supplement. A key aim of our project is to expand the scope of this pilot study and professionalise the distribution process via two major book publications. Bishop’s publisher, Farrar, Straus and Giroux, has contracted Professor Rosenbaum and I to edit a trade book of 150-200 Bishop postcards. While the pilot study centred on Bishop’s postcards at Vassar, research carried out at six additional archives (Harvard, the New York Public Library, the Rosenbach Library, Princeton, the Smithsonian, and the University of Delaware) during the grant will allow us to locate never-discussed postcards and to publish over triple the number from the pilot study in a book attractive to the general reader. Research on Bishop’s visual art undertaken at these archives will also allow us to complete a scholarly analytical edition. Our proposal for this analytical edition is currently under review for an advance contract at Harvard University Press, provisionally titled An Art of Looks: Elizabeth Bishop and Visual Culture. This second book will make a powerful case for approaching Bishop as an intermedial artist, and for expanding the Bishop canon to incorporate the many visual arts (postcards, photography, collage, watercolours, film and architecture) that Bishop practised. Alongside these book publications, we will work with Vassar College on organising two new exhibitions of Bishop’s postcards at sites important to Bishop’s travels: Paris, France and Sheffield, UK.  Rather than simply repeat the pilot exhibition, we will use the grant to create site-specific exhibitions with postcards relevant to each place, and will organise public-facing events to attract a diverse audience. Collaborating with colleagues at the Sorbonne University, we will design an exhibition at the Sorbonne Libraries and a number of creative writing workshops, along with an international symposium on Poets and Postcards. At the University of Sheffield we will work with the Rare Books Librarian to draw attention to the importance of visual ephemera like postcards, with the goal of inviting donations to the library’s collection. Our methodological insights on modern poetry as a visual art form and on the inter-relationship of poetry and other visual forms extend beyond Bishop Studies. Our project breaks down long established disciplinary walls, speaking not just to literary critics but to practitioners and scholars. To achieve this aim, we have assembled an advisory board representing multiple disciplines, and will mentor a RIA in cutting-edge interdisciplinary research.

UKRI Gateway to Research · FY 2025 · 2025-09

"What is the Universe made of, and why?" Sheffield's HEP programme addresses this fundamental question. There are two problems here: about 5/6 of the matter in the Universe seems to be made of yet undiscovered particles (dark matter), and the remaining 1/6 is mostly matter, not the 50:50 matter-antimatter mix we produce in laboratories. We search for dark matter particles in two ways: at the energy frontier, by searching for particles created in high-energy proton-proton collisions of the LHC, and in direct searches, attempting to observe these particles in the Galaxy itself. Our ATLAS programme searches for new Higgs bosons, and for particles related to the SM quarks and gluons. We also study processes involving the force carriers of the weak interaction, probing our understanding of the Standard Model (SM), and measuring the properties of the SM Higgs boson. We are contributing essential work to the upgrade of the ATLAS experiment required to take full advantage of higher event rates in future running of the LHC. In the LZ experiment, we search for evidence of dark matter colliding with Xenon atoms, and we are a world leader in the study of backgrounds originating from surrounding rocks, detector impurities and cosmic rays. The design of the next-generation Xenon detector (XLZD) is underway and it is proposed to host XLZD at the Boulby Underground laboratory in North Yorkshire. We are also constructing a detector based on quantum technology to be hosted in Sheffield to search for axions: another possible type of dark matter particle which cannot be detected at the LHC or in standard dark matter experiments. Why is the matter in the Universe all matter, not antimatter? The answer to this question lies in subtle differences between particles and antiparticles, an effect called CP violation. The CP-violating effects so far observed are not large enough to create the Universe we see. The most likely source for more CP violation is in the interactions of neutrinos. A key observation is that neutrinos have mass, and that different types of neutrinos can interchange their identities in flight. The T2K experiment made measurements of this and detected tantalising hints of CP violation. We plan to build on this work and study neutrino properties both in running experiments (T2K and SBND), and in designing the next generation of neutrino experiments (DUNE and HyperK). We have taken a leading role in developing tools to assist the neutrino community in processing and analysing data in the search for new physics and improving our understanding of how neutrinos interact. The group is committed to applying HEP technology to challenges in the industrial sector to maximise wider societal impact. We are a leader in the development and simulation of cosmic ray muon detectors for industrial applications. We recently established Geoptic, a company applying STFC know-how to improve safety in the UK rail sector and support carbon capture and storage in the international oil and gas sector. Our expertise in neutrons and machine learning is also being used to monitor and improve irrigation in water-scarce regions, and our experience in gamma-ray assay is being used to develop new methods to monitor soil health in sustainable farming practices. We are using techniques developed for ATLAS to contribute to the development of robotics with highly radioactive environments.

UKRI Gateway to Research · FY 2025 · 2025-09

Organic (carbon-based) semiconductors are leading to a more sustainable future in electronics. What sets organic based electronics apart is their cost-effective production through easy-to-use printing methods. They are also mechanically flexible and lightweight, making them ideal for unconventional device shapes. Additionally, these devices can be energy efficient, contributing to reducing power consumption, aligning with the goals of a sustainable energy landscape. The applications of organic electronics are diverse, including energy-efficient displays and low-cost photovoltaics for renewable energy generation. I specialise in optical spectroscopy and device physics of organic semiconductors. In my approach to research, I believe that merely understanding the potential of a molecule in isolation is insufficient. It is crucial to consider the context of the molecule within its environment and the diverse behaviours relevant to the timescales and energy-scales present in a functioning device. By integrating these considerations into opto-electronic models, we can facilitate more effective material and device design, thereby optimising their performance and functionality. Although organic based devices are already successfully incorporated into commercial products such as Samsung smartphones and LG TVs, their full potential remains untapped. For example, we have yet to develop stable blue high-performance organic light-emitting diodes (OLEDs) or electrically driven organic lasers. These advancements are hindered by a fundamental lack of understanding of exciton (electron and hole pair) dynamics within operational devices. Current research relies on photoexcitation (light) to probe exciton dynamics, which explains very well exciton dynamics in thin films. However, this method does not fully replicate true device operating conditions. The discrepancy arises because the excited states generated in electronic devices differ significantly from those induced via photoexcitation, primarily due to variations in the spin of the excitons generated. Therefore, a paradigm shift is needed in the study of exciton dynamics to unlock the potential of organic based devices. My proposed project will develop exciton dynamics models under actual device operational conditions and link these to performance and degradation of organic based devices. The project will study OLEDs using a novel device characterization methodology and currently available electro-optical techniques to unravel fast processes occurring in devices. The primary scientific outcome is to uncover key insights into how organic based devices operate. This involves understanding the mechanisms of exciton generation and emission in OLEDs. Specifically, I aim to obtain critical exciton parameters such as spin, energy, efficiency, and lifetime directly from the devices. By analysing these parameters and assessing their effects on OLED performance metrics (like efficiency, colour purity, and lifespan) we will be able to establish new guidelines for designing materials and devices. Moreover, this program will delve into device engineering methods for controlling exciton degradation mechanisms, which must be mitigated to realise significant breakthroughs in the field, such as stable blue high-performance OLEDs and electrically driven organic lasers. These achievements will impact direct industrial applications, especially in the development of displays that consume less power. Finally, I highlight that grasping the fundamentals of these emitting devices will yield broader implications for other organic based technologies. For example, sustainable organic solar panels currently face challenges on reducing non-radiative charge and exciton recombination which is critical to achieving high-performance conversion from light to electricity. This project holds the potential to ultimately understand this obstacle, promising advancements in the realm of solar energy technology as well.

UKRI Gateway to Research · FY 2025 · 2025-09

Overview and context ECOSOLUTIONS will train 39 transdisciplinary, solution-focussed PhD students who can apply systems-thinking to facilitate the delivery of a non-toxic UK environment and sustainable chemicals products sector. Chemicals are essential to society and the chemical industry is a major contributor to the UK economy yet chemicals pose a threat to biodiversity and human health globally and in the UK. To address this challenge a new way of working is needed where chemical impacts on whole systems, now and into the future, are considered and which has a greater focus on management and mitigation. Existing training programmes around chemical pollution take a single ecosystem approach and focus on chemical impacts. ECOSOLUTIONS is different in that it will deliver a training programme to develop graduates trained in systems-thinking and approaches to manage and mitigate chemical risks. They will be able to think across disciplinary boundaries and work across sectors. Aims and objectives ECOSOLUTIONS is an innovative and transdisciplinary training programme that has been co-designed with our 22 project partners to meet a systems thinking and solutions skills gap. It combines cutting-edge environmental science with approaches from other disciplines (natural, health and social sciences, engineering) to deliver a new approach to chemicals assessment and management that moves from describing chemical risk to a solution based, systems approach to prevent or manage both current and future impacts. It will deliver training that: implements a systems approach to chemical impacts on both humans and the environment; embeds cutting edge environmental science into future chemical-based scenarios and solutions; facilitates effective and agile approaches to pollution regulation and policy that cut across disciplinary silos.   Delivery and training ECOSOLUTIONS brings together 150 world-leading researchers and practitioners across the three partner institutions and 22 project partners.  We will train 39 PhD students via a 3 year 9 month training programme, co-designed, co-funded and co-delivered with our project partners to produce graduates that have the skills and knowledge to: (i) help the UK Government meet its target to deliver a non-toxic environment, (ii) support the design of sustainable chemical products and the development of a sustainable chemical manufacturing sector, and (iii) manage pollution to conserve biodiversity and protect human health.  All students within a cohort will undertake challenging research projects that relate to the same systems challenge (delivering non-toxic: urban systems (cohort 1), food systems (cohort 2), sustainable chemical production systems (cohort 3)) and will follow a core training programme providing knowledge and understanding of chemical assessment and management and supporting development of transferable and systems thinking skills. ECOSOLUTIONS graduates will be excellent researchers able to work across the natural, health and social sciences, engineering disciplines and across government, industry and third sectors. They will be innovative thinkers who can design safe chemicals and develop nature-based solutions for mitigating impacts. They will be equipped to effectively translate their work to a range of stakeholders via effective collaboration, networking and communication.

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

Cyber security is an increasingly serious issue particularly in domains such as finance, public services, medicine, and other high value targets.  Neurosecure brings together complementary expertise at the University of Sheffield and Forschungszentrum Jülich GmbH to enhance hardware security especially in low power smart sensor or smartphone applications.  It aims to address  vulnerabilities in next generation memristor crossbar array based AI hardware, arising from leakage paths, or other forms of malicious attacks to steal IP sensitive model weights and introduce classification errors. Neurosecure  explores Physically Unclonable Functions, PUFs, which are one of the most promising hardware-based security primitives available today. PUFs generate a cryptographic key “on-the-fly” based on the device-to-device variability of memristors that is inherent to a manufacturing process and cannot be replicated. Our proposed technique aims to make the relationship between the challenge and its response even more obscure for machine learning to hack in a conventional PUF. The teams will carry out characterization of memristors at their respective sites, supply data to each other to examine the feasibility of their proposed technique against adversarial attacks. Mutual visits are planned to develop collaborative links that can provide a route towards manufacturing which is a core competence of FZJ who have previously heterogeneously integrated memristor crossbar arrays on 180 nm CMOS.

UKRI Gateway to Research · FY 2025 · 2025-09

Modern electronic devices—from smartphones to critical infrastructure systems—rely on hardware-based security foundations called "root-of-trust" to protect sensitive data and operations. However, current security-designs have a fatal flaw: once compromised through physical access, devices become permanently unusable and require complete replacement. This creates significant economic costs, security vulnerabilities, and operational disruptions across homes and industries. Physical access attacks are becoming increasingly common, targeting a wide range of systems, from industrial control systems to personal devices. Current security approaches force organisations to discard expensive equipment after any suspected compromise, creating unsustainable costs and supply-chain vulnerabilities. This raises an essential question: ‘How can we maintain security even after device tampering and dramatically reduce replacement costs and improve system resilience in the process?’ Our research challenges this fundamental limitation and addresses this question by developing dynamic-hardware-security-systems that can detect attacks, isolate-threats, and recover functionality without device replacement. Unlike traditional static security that fails permanently when breached, our approach investigates real-time adaptation and ‘self-healing’ capabilities through innovative hardware and software integration. This collaboration between the UK-and-Germany combines the University of Sheffield’s significant experience in advanced cryptographic hardware research with WIZnet’s deep expertise in secure embedded systems and manufacturing security. The partnership addresses growing concerns about semiconductor supply chain security and manufacturing vulnerabilities that threaten both nations' economic and security interests. The broader-impact extends beyond technical innovation. For policymakers, this research supports digital sovereignty goals by reducing dependence on device replacement and strengthening domestic security capabilities. For industry, it offers pathways to more resilient products and reduced security maintenance costs. For the public, it promises more secure and longer-lasting devices that better protect personal data and privacy. This feasibility study establishes foundational concepts for a transformative-security paradigm that could reshape how we design, manufacture, and deploy secure systems across critical-infrastructure, consumer electronics, and defence-applications.    

UKRI Gateway to Research · FY 2025 · 2025-09

Microsatellite repeat expansion disorders are a group of over 50 neurological conditions that collectively affect 1 in 3,000 adults worldwide. There is no cure and in addition to unmet medical needs, they lead to profound distress for carers and economic burden in an ageing world population. Fragile X-associated tremor/ataxia syndrome (FXTAS) is a debilitating neurodegenerative disorder characterised by progressive loss of nerve cells in the brain, tremor, balance problems, cognitive decline and death within 5-25 years from symptoms onset. It is more common in males than females over 50 years of age and manifests in people carrying 55-200 microsatellite repeats of the trinucleotide CGG in the fragile X mental retardation 1 (FMR1) gene. The precise mechanisms leading to disease are still being elucidated, however one key driver of neuronal injury involves production of abnormal toxic poly(glycine) repeat proteins known as FMRpolyG. FXTAS affects approximately 1 in 8,000 people. Symptomatic treatments only can be provided to patients. They include beta-blockers and anti-epileptic medications, psychological counselling or rehabilitative speech, occupational and physical therapies. Developing a disease-modifying therapy that treats the root cause of FXTAS is therefore of paramount importance. We recently developed promising gene therapy approaches for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a spectrum of other incurable neurodegenerative diseases caused by GGGGCC microsatellite repeat expansions in the C9orf72 gene. They work in cell and animal models by diminishing the transporter function of Serine/Arginine-Rich Splicing Factor 1 (SRSF1) that carries disease-altered repeat RNA molecules from their synthesis site in the cell’s nucleus into the surrounding compartment, the cytoplasm, where they serve as instruction manuals for the manufacturing of faulty and toxic proteins. This work also led to granted and pending patents as well as to founding Crucible Therapeutics, a University of Sheffield spinout company developing SRSF1-interfering gene therapeutics with a potential clinical trial envisaged for C9orf72-ALS/FTD patients within the next few years. In this grant proposal, we present pilot data showing that lowering SRSF1 also reduces the production of toxic FMR-polyG proteins and restores the growth of FXTAS cell models, supporting the investigation of a repurposed application to FXTAS. We now aim to test two SRSF1-interfering gene therapy modalities, based on viral and non-viral approaches, to reduce the cytoplasmic transport of CGG repeat transcripts and production of toxic FMR-polyG proteins in disease-relevant models. The main objectives of the research proposal are to: Aim 1: To demonstrate the neuroprotective potential of lowering SRSF1 in vitro in nerve cells grown from FXTAS patients. Aim 2: To demonstrate the safety and efficacy of lowering SRSF1 in vivo in FXTAS mice. Aim 3: To identify all changed RNA molecules to understand the global mechanisms protecting nerve cells from death and assess potential inaccurate effects in nerve cells grown from patients and in mouse brains treated with SRSF1-interfering gene therapeutics. Overall, the research proposed here aims to expand our gene therapy approaches developed for C9ORF72-ALS/FTD for potential future application to the treatment of FXTAS patients. If successful, it will generate a robust preclinical proof-of-concept package allowing protecting new intellectual property and incentivise future translational funding or private investments to fast-track a clinical trial for FXTAS patients. Our work is also regularly presented and discussed in outreach events involving local schools, the public and patients with neurodegenerative conditions.

UKRI Gateway to Research · FY 2025 · 2025-09

As the number of people waiting for or receiving a diagnosis of dementia increases, urgent attention is needed to support independent living across community and residential care. The BRIDGES for Dementia network (Building Research Innovation co-Developing Greater Empowerment and Support for people living with Dementia) will build research innovation communities that put empowerment at the heart of supporting people to live life on their own terms. The network's approach is anchored in partnerships with people living with dementia; we will drive the development and use of adaptive technologies that evolve alongside individuals and families, addressing the progressive changes in abilities such as memory, speech, and sensory processing throughout their dementia journey. Whether it is tools to support word-finding, platforms to engage with music or the arts, or new intuitive ways to interact in the face to face or online world, we envisage the network to encourage the co-design of new or adaptation of existing technology that empowers people living with dementia to be in charge of what they want to do and how they want to remain as integral parts of their communities. The BRIDGES for Dementia network integrates expertise across disciplines including languages, arts and humanities, build environment, computer science, engineering, medicine and population health spanning diverse clinical and social contexts. Led by researchers with transdisciplinary experience in co-design and participatory approaches, the network partners with organisations to invigorate research incorporating lived experiences and to implement innovative technologies at scale. Our dual integrated activity programmes of co-design for transdisciplinary learning and equality, diversity and inclusion inform research across four key themes: Indoor and outdoor spaces Arts, sports and culture In-person and online communication Digital technology development and translation These themes prioritise tools that enable individuals with dementia to feel agency and “in control” as they continue to have an active role in a rich daily life, and technologies that open up the world rather than dictate a limited set of activities or interactions. The network will stimulate and build new interdisciplinary and transdisciplinary communities driving tool and technology innovation to support people living with dementia to live independently. It will host technology design sandpits and conferences, facilitate researcher upskilling through lived experience masterclasses, and fund a wide range of scoping, pump-priming, and feasibility studies. The wide network membership will include organisations with expertise across clinical and community life including community health and wellbeing, supermarkets and town centres, cultural institutions, councils, volunteer networks, support agencies and directly those with lived experience. Together, our activities will develop the transdisciplinary interface and synergies between lived experience, technology design expertise, and community organisations and will co-produce rich and engaging technology design agendas for the future.

UKRI Gateway to Research · FY 2025 · 2025-09

In both cellular biology and chemistry, many critical processes that affect our quality of life are not yet well understood. These processes happen within systems surrounded by high levels of environmental noise. Enter the nitrogen-vacancy (NV) defect in diamond — an ambient atom-like probe that yields single photons, particles of light, correlated with its spin property. Capturing single photons enables the spin-based sensor to function as an extremely sensitive monitor of its immediate environment, as information can now exit the environment, free from electromagnetic disruption. This quantum sensing technology has already provided a unique window on processes within cellular structures and chemical reactions. There is now over a decade of scientific evidence that this technology would transform areas where classical techniques have stalled and there is unmet demand. However, to date, these sensors are constrained to physics laboratories with complicated optics, mechanics, and associated infrastructure. They cannot be used at scale or by non-physicists who would benefit from this transformative technique. In my fellowship, I will take the tools used to produce computer chips to level-up this solid-state sensor. Semiconductor tools, refined over half a century to possess unmatched control and yield, would evolve solid-state spin-based techniques into manufacturable, robust, low-power, and ultimately low-cost sensors by: (i) lithographically depositing diamond in micron-scale regions to realise a 64-pixel spin-based sensor array (the current state-of-the-art is two pixels), (ii) routing pixel information at micron-scale densities using manufactured silicon photonics, (iii) using robotics in new ways to produce milliradian-accurate fields to sensitise these systems where current vector magnet technology fails (iv) combining the above with silicon microelectronics to extract and process nanosecond sensor information at unprecedented efficiencies. The primary aim of my fellowship is to demonstrate a manufacturable spin-based sensor to replace bulky experiments: routing and controlling an optically-active defect using foundry photonics, microelectronics and robotics, making the sensor smaller and therefore more accessible. My secondary aim is to unlock improved sensitivity through robust control, photonic enhancement and quantum enhancement. The objectives to achieve these aims are as follows: Photonic integration of the sensor: the rise of silicon quantum photonics has shown that commercial foundries are the most reliable way to achieve scale and robustness in quantum experiments. Co-integration of precise robotics to provide robust three-dimensional field alignment. Quantum-enhanced readout: engineering the spin energy levels with the precise field produced by the robot removes non-spin-conserving emission. This allow photonics to increase the sensor readout rate. Benchmarking performance against the commercial spin-based sensors offered by Project Partners to demonstrate the benefit of this scalable technology. Full-stack design of control and user interface. Broad usability feedback to ensure the sensor is ready to move forward into commercialisation by fellowship end. By fellowship end, I will use the newly-manufacturable quantum sensor to demonstrate two key real-world applications: mapping signals in a single biological cell to gain insight into disease pathways and imaging a single molecule, an important advance for nanolitre chemical analysis to replace bulky spectroscopy apparatus. Collaborating with the pioneering researchers in this field and those experienced in developing market-ready products, we will take the steps that put solid-state spin-based sensors into both the hands of medical practitioners, where adoption has the potential to enable precision in disease diagnosis, and research chemists, developing clearly scalable use cases in spectroscopy across the chemical industry.

UKRI Gateway to Research · FY 2025 · 2025-09

Steel is the world’s most important engineering material, with the often stated “If it’s not made of steel, it’s made using steel”. The need to reduce CO2 emission from the steel industry is patently obvious and is driving global investment in steel production; the UK is making an abrupt change from the blast furnace to electric arc furnaces, which primarily use scrap steel as a feedstock and emit just a fraction of the CO2 content. This brings marked problems from the increased residual (“tramp”) elements (Cu and Sn) in the final steel. Daehn et al. forecast that by 2050 all new steel will contain more Cu and other tramp elements than can be tolerated and will thereby be rendered useless. This is a ticking time bomb in the steel industry. Whereas these elements are hitherto regarded as deleterious to hot shortness, ductility and toughness, we can make a virtue out of a necessity and turn these intruders to our advantage through alloy design for impurity tolerance. The metallurgical reasons for the effect of residual elements are far from clear. Residual elements have a complex effect on the mechanical properties of the steel, with significant contradictions in the literature, and a very curious observation that both the proof stress and tensile strength increase linearly with Cu content with the same slope with a small decrease in ductility. We urgently need an abrupt advance in knowledge to mitigate the role of residuals, but this will not be brought about by the classic “knowledge informed trial and error” approach: the number of variables is simply too large. The only way forward is to understand the fundamental role of residuals at the atomic scale and how they interact with other alloy additions, with migrating and transforming boundaries.  This will open up robust strategies for mitigation, and indeed turn the presence of residuals to an advantage. Therefore, we will have to develop theory and modelling to understand the role of single and multiple solutes, both in the lattice and at interfaces. The use of fast and accurate machine learned atomic cluster expansion (ACE) interatomic potentials will enable the calculation of these interactions in a way that was inaccessible to previous computational techniques. Preliminary modelling work has shown an interesting interaction between Cu and Ni in Fe, indicating that Cu on its own will segregate to the boundary, but when combined, the presence of Ni will reduce the tendency of Cu to segregate. This brings a very different view on the role of Ni in Cu bearing steels than hitherto considered. Model alloys will be manufactured with targeted tramp element contents based on the outcomes of the theory and on initial proof of concept work. High temperature simulations will be made of solubility, grain boundary segregation, work of separation with a view to concentrate on the synergistic and competitive behaviour of tramp elements (Cu, Sn) and additions (C, Mn, Ni, Si, Cr) in combination. Laboratory experiments will accurately simulate the full industrial process, with site-specific high spatial resolution techniques through a combination of TEM and APT to comprehensively characterise the grain boundary segregation, solute clustering, crystal structure of precipitates, composition and coherency at the atomic scale.  This new understanding will feed into industrial case studies and plant trials to deliver new tramp element tolerant green steel.