University of Nottingham

UKRI Gateway to Research · FY 2025 · 2025-06

The transition to PI is the largest career adjustment academics experience. The recent Research Culture: A survey of new PIs in the UK (eLife, 2019 PMID: 31538616) highlights the huge challenges faced by new investigators; establishing their identity, securing funding, meeting teaching and administrative demands, limited staff and fragmented institutional support. This survey laid bare a range of barriers: Funding: Over 40% of New Investigators had no external funding. Grant success: Between 2012-2018 numbers of new investigators externally funded within their first year declined annually (from 95% in 2012 to 30% in 2018). There have been no data collected since 2018. Staff: Up to 50% of New Investigators did not have a postdoc, and up to 75% did not have a RA or technical support. PhD provision: New Investigators found it difficult to recruit PhD students who often favour established research groups. Facilities: 45% of New Investigators were dissatisfied or indifferent regarding their space and facilities. Current systems are not adequate to sufficiently support the success of UK-based New Investigators. Crucially, this undermines efforts to deliver world-class ideas, impact. We aim to overcome these barriers through the formation of NOBLE. A bottom-up, community-led network of New Investigators providing the infrastructure, support, training, and access to facilities required for New Investigators and those approaching independence to succeed. In doing so, NOBLE will drive collaborative, discovery science and bring together teams to solve the most pressing questions across the fields of obesity and metabolism. To this end, our 5 overarching objectives reflect the multidisciplinary nature and inclusive culture at the heart of NOBLE: Bottom-up collaboration through a UK-wide, community-led network sharing resources and protocols, facilitating technical development, knowledge exchange, and training. Interdisciplinary network to establish new cross-cutting collaboration and drive discovery bioscience. Self-supporting community through flexible funding provides collaborative network grants, skill sharing, and training opportunities. Co-created training providing new investigators, and underrepresented groups with professional skills for long-term future success. Building capability to provide opportunities for all new investigators to succeed with access to world-leading facilities and industry expertise. A joint initiative by the University of Nottingham and Nottingham Trent University, we build on our established reputation as a centre of excellence in discovery bioscience and doctoral training. Together, we will offer network members access to expertise, models, and facilities as a central, accessible ‘hub’. Further, in collaboration with project partners Sygnature Discovery and We Are Pioneer Group we will provide network members with training and support from industry leaders in drug discovery and innovation. Through these tools, our goal is to eliminate the dysfunctional experience faced by New Investigators. By supporting a collaborative network, with open access to expertise, facilities, and training we aim to drive researcher development and shared success. We believe this initiative will create a lasting impact. It will establish a new paradigm for how New Investigators can work within UK bioscience, whilst simultaneously increasing the quality, and output of the sector.

UKRI Gateway to Research · FY 2025 · 2025-06

This project pilots a novel method for testing historical judgement that has the potential to transform how scholars and policy-makers research, assess, and learn from the past. Gaps in the historical record present significant challenges but also valuable opportunities. Instead of avoiding gaps, scholars and practitioners can test the accuracy of inferences about the past by carefully outlining their assumptions and explicitly predicting what they believe to have occurred in the absence of evidence. Subsequent discoveries or declassifications can then be used to assess the accuracy of these hypothesised explanations and, when collected and analysed, enable better predictions about the past, or “retrodictions.” The importance of making and testing predictions about the future has been well documented. Yet there has been limited effort to make, collect, and assess predictions about the unknown past. Our interdisciplinary pilot project addresses this gap, drawing on the expertise of political scientists, historians, psychologists, and relevant practitioners to establish a proof of concept for how to identify, assess, and improve the practice of retrodiction. As a pilot study, it will test the viability and power of retrodiction, aiming to answer three questions: what are the most effective ways to collect and assess retrodictions? What lessons can be learned from accurate and inaccurate predictions about the past? How far are these lessons generalizable? By answering these questions, we will provide a springboard for a new research agenda on retrodiction. We will work with our Project Partner (Moody’s Analytics), key stakeholders (Forecasting Collective [FC], HM Treasury), and three supporting Labs (the Rights Lab, the Wisdom and Culture Lab, and the Decision Neuroscience Lab) to collect and test retrodictions in three different subject areas: human rights, nuclear proliferation, and sovereign debt. These choices reflect salience and relevance, availability of data, and our own expertise. As few testable examples exist, we will identify and test up to 300 retrodictions. Our methods for data collection include novel retrodiction tournaments. We will assess the accuracy of historical judgement by using existing forecasting criteria and standards supported by industry experts. Our findings will generate a novel dataset for testing and comparison. We will identify lessons from our findings, examine the rationales for predictions, and share findings with forecasting experts to establish broader generalisations. This project’s contribution and value reflect the creation of a new mode of inquiry to generate original data and novel insights, moving beyond the constraints of only predicting the future. Using retrodiction to test existing hypotheses about why forced labour persists or how states manage sovereign debt, for example, may help to improve understanding of both subjects and refine thinking about enduring real-world problems. By providing innovative methodologies, we aim to assess the efficacy of previously untestable work, promote better scholarly practice, and improve historical judgement across multiple disciplines. We believe this pilot can set a new research agenda by promoting a more rigorous, testable set of methodologies that will benefit scholars and policymakers who seek a clearer, richer, and more usable past.

UKRI Gateway to Research · FY 2025 · 2025-06

In order to meet the UK's net-zero goals, new energy storage technologies that can store enough energy for large transport applications on land, air and sea will be required. The lithium-ion batteries that have revolutionised the EV market lack the gravimetric energy density needed for such high-energy applications. Lithium-sulfur batteries exploit redox reactions on sulfur-based positive electrodes, rather than the metal oxide found in lithium-ion batteries, offering drastic enhancements in energy density and potentially game-changing progress in electrified transportation. The most pressing challenge is to extend the cycle life to the thousands of cycles needed in transport applications. In current systems the lithium metal electrode reacts with dissolved sulfur species found in the liquid electrolyte resulting in degradation and hindering long-term cycling of the battery. Gelion has pioneered the quasi-solid-state lithium-sulfur battery, which contains a high concentration electrolyte that forces the sulfur and its intermediates into the solid-state, significantly improving the battery performance by preventing sulfur loss from the electrode. However, the reaction between the lithium metal and the cell components remains problematic for long term use and cycle life does not meet requirements for large transportation applications. The University of Nottingham and Gelion have co-developed this proposal to tackle this problem by developing hybrid electrolyte cells. This ambitious target can only be met through the synergistic collaboration of our teams. In the hybrid electrolyte cell, lithium metal is protected from reacting with the cell components by coating it with a solid electrolyte, which is in turn separated from the positive electrode by the high concentration electrolytes used in the quasi-solid-state lithium-sulfur battery. Degradation reactions between the solid and liquid electrolytes are expected, and these will be studied using fundamental chemical and electrochemical methods to understand the mechanism of these unknown reactions and determine how they impact the electrochemical properties of the cell. The impact of these degradation processes on cell performance will be determined and mitigation strategies will be employed, such as the addition of protective coatings onto the surface of the solid electrolytes to stabilize the solid-liquid interface. We aim to build a lab-scale prototype cell that can achieve hundreds of cycles with high capacity retention. The programme will yield significant new intellectual property which will be captured through close collaboration between the academic and industrial partners for exploitation and commercialization of the quasi-solid-state lithium-sulfur battery within the UK.

UKRI Gateway to Research · FY 2025 · 2025-05

Human brain health has been revolutionised by techniques like MRI, which provide a non-invasive window on brain structure. However, in many diseases, structure appears normal, and it is changes in the function of brain cells that underly symptoms. It follows that next generation healthcare critically requires the development of techniques to measure brain function. A good example is epilepsy, where abnormal electrical activity in neural networks underlies symptoms. Epilepsy affects ~900,000 people in the UK and in ~30% of cases, symptoms are not controlled by medication. Patients become candidates for surgery, where the tissue generating seizures is removed. Extensive assessment is required to identify the regions to be removed, however this is a significant challenge. EEG (the standard technique to diagnose epilepsy) has poor spatial precision and cannot pinpoint the target regions. MRI doesn't always detect abnormalities and when it does, multiple abnormalities are often found, and we don't know which is responsible for seizures. The "gold standard" measurement involves placing electrodes in the brain. This gives a measurement of activity with the highest possible sensitivity and spatial precision. However, it requires major surgery. We will develop a new technology, which will be completely non-invasive, yet will rival the performance of invasive electrodes. Our system will use "quantum" sensors, which exploit the quantum properties of atoms to detect magnetic fields generated by brain activity - a process called magnetoencephalography (MEG). MEG is already a proven tool in research and has significant clinical applications - especially epilepsy. However, conventional scanners use low temperature sensors. Consequently, sensors are kept a long way from the head - limiting sensitivity and spatial precision. Our system will use sensors called OPMs, which can detect magnetic fields without low temperature. OPMs can be sited much closer to the scalp, providing higher sensitivity and spatial accuracy. Furthermore, because OPMs are very small, we can pack large numbers together in a 'high density' (HD) array, further improving sensitivity and spatial precision. Theory suggests that our new system, which we call "HD-OPM-MEG" will rival the performance of implanted electrodes. There are significant technical challenges that must be overcome to make HD-OPM-MEG work. We must understand the spatial patterns of magnetic field generated by the brain, and how those patterns differ in children and adults - this will help us design the best possible sensor arrays. We must develop novel devices to ensure that the magnetic fields we measure are accurate. We also need new tools to ensure that magnetic interference cannot impact our data. Having collected data, we need techniques to turn the measured fields into 3D images of activity - this includes novel methods to determine where on the scalp our OPMs are located. We will solve these fundamental problems; we will then undertake studies in healthy children and adults, to show that our new HD-OPM-MEG system can map electrical brain function with performance that has never before been achieved using a non-invasive technology. Finally, we will apply our system in patients with epilepsy, showing that we can map the regions responsible for seizures with a precision comparable only to that of invasive electrodes. HD-OPM-MEG will be a non-invasive imaging technique with unprecedented performance. Although our demonstration will be in epilepsy, this technology will revolutionise the capability of imaging across a wide range of neurological and psychiatric conditions.

UKRI Gateway to Research · FY 2025 · 2025-05

Asthma is a common lung condition with symptoms such as shortness of breath, wheeze, cough and chest tightness. Approximately 10% of individuals with asthma suffer from a severe form of the disease. They struggle to control their symptoms despite high levels of medications, resulting in lower quality of life, risk of hospitalisation and even death. New therapies are needed for this group of patients. The lungs produce the jelly-like substance mucus that acts as a gatekeeper controlling access of harmful agents (particulates, microbes, and toxins) into the body by trapping and removing them via the mucociliary escalator. However, in asthma, accumulation of mucus with abnormal properties can plug the airways worsening symptoms (known as exacerbations). The framework of mucus is provided by large molecules called mucins; in the lung there are two types of mucin (MUC5AC and MUC5B). We and others have shown that MUC5AC is increased in airway mucus in asthma. Importantly, we identified genetic changes near the genes encoding MUC5AC and MUC5B that alter the levels of these proteins and affect the risk of severe asthma. We propose a highly integrated, multidisciplinary research programme that will provide new understanding of the mechanisms that lead to the increase in mucins and how this changes the properties of the mucus in severe asthma which could lead to the development of new treatments. Main objectives: 1. Determining the genetic changes that affect MUC5AC or MUC5B expression or structure and increase risk of severe asthma. We will assess prioritised genetic changes to pinpoint which may alter the type of MUC5AC or MUC5B produced and at what level including how this is related to the risk of severe asthma. This will provide vital clues about the mechanisms involved in MUC5AC and MUC5B production. 2. Testing the effects of these genetic changes in lung cells. To understand how these genetic changes cause differences in the amount or properties of mucus proteins, we will study these genetic changes in lung cells from asthma patients. Lung epithelial cells can be grown in the laboratory to mimic the airway lining in the lung, enabling study of the different cell types present, their development and function, as well as the composition and properties of the mucins and mucus produced. We will also investigate the effects of exposing cell models to viruses known to trigger asthma exacerbations. Having identified genetic changes, we will try reversing or removing some of these changes in cell models and in human lung slices to confirm their effects on mucus production and properties. This will provide new novel targets for drug development. 3. Testing the effects of genetic changes on mucus production and composition in severe asthma patients before and during exacerbations. We will use lung biopsies and sputum samples from patients with severe asthma to identify the effects of genetic variants on the regulation and mucus composition in patients when stable or when having an exacerbation. Access to other translational studies, including intervention studies, will provide further understanding. We are bringing together international leaders in respiratory research and are employing state-of-the-art techniques spanning biology and physics to understand the mechanisms that control how mucus is regulated in our airways, how it contributes to severe asthma and how we might target it for therapeutic benefit.

UKRI Gateway to Research · FY 2025 · 2025-04

Climate warming is thawing permafrost in polar regions resulting in increased methane (CH4) emissions and as CH4 is a potent greenhouse gas, this exacerbates climate warming and its associated impacts. Additionally, rising atmospheric CO2 concentrations can cause increased CH4 emissions via altered plant soil interactions. Increasing CH4 emissions from thawing permafrost has been suggested as one of the drivers of the strong increase in atmospheric CH4 concentrations during recent decades and is expected to become an even stronger emitter of CH4 this century. However, data that quantifies CH4 emitted from tundra landscapes is limited - both the area of permafrost wetlands that are thawing and the resulting regional increases in CH4 emissions requires investigation urgently. This project is designed to quantify how permafrost thaw has contributed to rising atmospheric CH4 concentrations and to predict how these emissions will change in the future. One of the project targets is to use satellite measured atmospheric CH4 data to generate maps of CH4 emissions through time. To evaluate these in the context of ground measurements and permafrost thaw, we will compare them to up-scaled data of ground and drone-based measurement of CH4, as well as to regional estimates of areas affected by permafrost thaw using satellite data capture of the land surface. To predict how CH4 emissions may change under future warmer and higher CO2 conditions, growth room experiments mimicking future climate conditions will be used to determine how vegetation responses to these new conditions impacts CH4 emissions. In combination with detailed vegetation maps from drones and satellite data, this data will be extrapolated to the landscape to quantify CH4 emission associated with vegetation responses to future climate scenarios. The geographical focus of the research activities will be regions with large expanses of permafrost wetlands in Fennoscandia, Canada and Russia. Field work (ground and drone measurements) will be carried out in Sweden and Canada only, while the satellite data analysis will enable us to carry out work on the extensive permafrost wetland areas in Canada, Fennoscandia as well as west Siberia. The satellite data used for the research is freely available from the European Space Agency and the project team has all the relevant skills to process the data to generate the outputs needed and integrating the satellite data with the field and experimental data. The main outputs from this project will be: (i) regional estimates of permafrost thaw and CH4 emissions from permafrost wetlands and (ii) spatially explicit quantitative understanding of key processes controlling current and future CH4 fluxes from permafrost wetlands. Taken together this project will deliver quantification of the contribution of permafrost wetlands to global atmospheric CH4 concentrations over the last two decades and an assessment of the vulnerability of these to future climate warming. This information is needed for realistic global climate predictions and underpins climate mitigation actions.

UKRI Gateway to Research · FY 2025 · 2025-03

My 7-year vision for this fellowship is to design, build and test hair-thin imaging devices that can better see diseases such as cancer in previously inaccessible areas of the body. Cancers occurring deep in the body are hard to detect due to their inaccessibility via natural orifices: ovarian cancer has a 50% 5-year survival rate while for pancreatic cancer this is just 1%. Early detection of these cancers could allow surgeons to treat or remove them before they spread, dramatically improving survival. However, early cancer is only subtly different to healthy tissue so accurate detection requires very high resolution imaging, much higher than MRI or X-rays. Imaging using light achieves this resolution but requires the camera to be very close to the tissue being examined, which is difficult for internal organs like the pancreas. In this fellowship, I am overcoming this limitation by developing a new generation of devices that take images through optical fibres: hair-thin pieces of glass that fit inside tiny needles and can be harmlessly inserted deep into the body. Progress: During the first 3 years of my fellowship I have built a team of 7 people (3 post-docs, 3 Ph.D. students, 1 intern) and led them to develop two new technologies that enable my overall vision. First, a nanotechnology technique for making tiny (<0.1mm) lenses and attaching them to tips of hair-thin optical fibres. These lenses enable our fibres to perform special types of imaging that improve contrast between healthy and diseased tissue compared to conventional imaging. Second, a new AI technique that corrects for image distortion created by the optical fibres as they bend while in use. This is analogous to 'seeing through frosted glass' by precisely reversing the scattering effect of the frosted glass surface. Together, these two technologies enabled me and my team to build a first-generation prototype and led to 10 journal publications (2 under review), 7 conference presentations and numerous invited talks (Arizona, St. Etienne, ICAMD in South Korea, Bath, Southampton, Cambridge). My reputation in the field has grown, and since 2022 I have sat on 3 committees for major conferences, sat on a group updating NHS Endoscopy guidelines, written an invited piece for Science China, China's domestic flagship Science journal, and been in working groups for the new ARIA funding agency and the Photonics21 partnership that defines Horizon Europe work programmes. To support my growing team I have attended two major leadership training courses and receive regular leadership coaching. I run regular lab-meetings and skills-focussed away days to mentor my team, and co-developed with my team a 'lab charter'. Plan for renewal: I will address two key challenges towards achieving the overall vision. First is the need to minimise false positives and false negatives to avoid cancer being missed or prevent unnecessary life-changing treatments. To do this, I will probe multiple biological features of tissue simultaneously by multiplexing several types of imaging in one fibre using the multi-layer lens technology we have developed. Second is the need for the instrument to be fast and robust for clinical usage. To address this, I will work with collaborators in Zhejiang to combine their new ultra-fast fibre characterisation technique with the new AI techniques we developed and test on ex vivo pancreas tissue. I will also prepare larger consortium-based bids (EPSRC Network, Horizon) to bring together the national and international community on ultrathin imaging and work with industry partners to accelerate clinical translation (MRC DPFS, KTP, iCASE). I will support my growing team to develop and fund their own research projects via pump-priming, or as Researcher Co-Investigators. Long term, I envisage a versatile endoscopy platform: wherever a needle can reach there will be an opportunity to perform a smart 'optical biopsy', offering unprecedented vision deep in the body.

UKRI Gateway to Research · FY 2025 · 2025-03

Violent crime has enormous costs for society. There are 614,400 incidents of violence each year in the UK, costing the economy £29 billion. Most of this violent crime is committed by people with antisocial personality disorder (ASPD), a type of mental disorder emerging in youth and lasting throughout life. These individuals engage in violent and antisocial behaviour from childhood. Many have difficulties with empathy, that is, understanding and responding to other’s thoughts and emotions. Evidence for good treatments is poor in both groups. About one third of these people also have a more severe form of ASPD, called psychopathy. They struggle greatly to empathise with others, commit more serious and violent crime, and respond especially poorly to treatments, compared to those with ASPD without psychopathy. A better understanding of the empathy abnormalities (and their underlying biology) within these groups of violent offenders is needed to develop options for more effective treatments, including medications. There are two key types of empathy — cognitive empathy, which is the ability to understand what other people are thinking and feeling, and affective empathy, which is responding emotionally to others' emotions. Some studies suggest that problems with affective empathy drive violent offending by people with ASPD, especially in those with psychopathy. However, studies examining both cognitive and affective empathy in samples of violent offenders with ASPD, with and without psychopathy, are lacking. In this study, I will address this problem. I will compare both cognitive and affective empathy in violent offenders with ASPD with and without psychopathy to empathy in healthy non-offenders. I will measure this by having participants watch and respond to videos showing realistic social scenarios and assessing their responses to others' problems and emotions. Along with this, I will use cutting-edge technologies to further understand the brain abnormalities underlying empathy problems in people with ASPD with and without psychopathy. Firstly, I will use a new technology called OPM-MEG, which is the world's first 'wearable' brain scanning technology. This allows for measurement of brain activity, while performing tasks, like watching and responding to the video in this study, outside of a standard MRI scanner. This is especially useful in some groups, including those with ASPD, who have difficulty focusing on such tasks in a noisy MRI scanner. Secondly, I will explore the role of the neurochemicals glutamate and GABA. I will do this using a high-resolution MRI scanner, measuring glutamate and GABA in parts of the brain that are especially important in empathy. This step requires participants simply to lie still in the scanner. Finally, in a small group of adolescents who have offended, I will show that these investigations can also be used in young people. This is important for finding future interventions in young people at risk of developing ASPD in adulthood. This work could be a major stepping stone in developing treatments for ASPD and psychopathy. By linking empathy abnormalities to underlying brain biology and chemistry, we can start to develop precise, effective treatments. Such treatments would first be tailored for individuals with ASPD with psychopathy or without psychopathy. As our understanding increases, they would eventually be tailored to the specific individual. This approach, known as 'personalised medicine', is increasingly recognised as the ideal approach across both mental and physical health. The long-term benefits to society of reducing violence are enormous.

UKRI Gateway to Research · FY 2025 · 2025-03

Climate change and related extremes represent one of the most significant challenges of the twenty-first century. Yet lived experiences of climate change vary, with negative impacts disproportionately felt by marginalised populations who have historically contributed the least per capita emissions. The proposed study advances understanding of an under-researched topic within this urgent context: the role of colonial power and knowledge in shaping climate adaptation and vulnerability past and present. Current analyses and practices of adaptation rarely investigate deep histories of colonialism and repeated disaster, but a historical lens is particularly vital here as there is now mounting concern that today's adaptation strategies are resurrecting ideas and initiatives propagated through colonialism, for example by undermining local adaptation strategies (Eriksen et al. 2021; Gengenbach et al. 2022). At worst, this risks reproducing rather than reducing the vulnerability of populations that are already on the frontline of the climate crisis (Schipper 2020). This research aims to build new, usable pasts of climate and society in three regions of southern Africa (southern Mozambique, western Zimbabwe, southern Malawi), where the imperative of climate change adaptation has been underscored by recent cyclone and drought disasters. Specifically, it will draw upon diverse archival collections to examine the origins and transformation of climate knowledges and adaptation practices during the 19th and early-20th centuries, when colonial rule intensified. Together with project partners and local stakeholders, it further aims to elevate this historical knowledge of climate coloniality into new interaction with climate foresight to drive equitable and sustainable adaptation. The data and findings generated from these historical deep dives will be interrogated through fresh theoretical and empirical lenses, addressing the following research questions: 1) How did climate coloniality emerge in different settings via the (re)construction of climate knowledges and imposition of material practices? 2) What was the multidirectional nature of interaction between climate knowledges, adaptation strategies and recurring climatic extremes? 3) How did Africans resist or influence climate thinking amongst Westerners despite colonial relations of power? 4) How can these climate histories be integrated into climate foresight planning and scenarios to drive equitable and sustainable climate change adaptation? The study is transdisciplinary in scope, spanning environmental and climate history, historical geography, climate foresight, African studies, historical climatology, disaster studies, climate science and the history of science; fields that will be drawn upon and integrated. The scale of the research will yield the place-based insights needed to develop geographically and culturally specific climate histories, but also the comparative understanding required to develop a theoretical framework of the emergence of climate coloniality. This mixture of approaches will create innovation in the environmental humanities, and - through its impact - help place the SHAPE (Social Sciences, Humanities and the Arts for People and the Economy/Environment) disciplines at the fore of efforts to address climate change. The working practices and theoretical framework developed through the project will have wider transferability across former colonial contexts, boosted through the project's partnerships with the UN Food and Agriculture Organisation and leading foresight planners.

UKRI Gateway to Research · FY 2025 · 2025-03

One of the seven Millennium Prize Problems listed by the Clay Mathematics Institute is the Birch and Swinnerton-Dyer conjecture.  This is one of the biggest open problems in number theory.  By now, we know some results but a complete proof still seems far away -- and there are generalisations that put this at the very heart of a vast programme to understand how to solve equations in integers.  The aim of this proposal is to reformulate the Birch and Swinnerton-Dyer conjecture and to put it into a new perspective. Let A and B be two integers and consider the equation y2 = x3+A x+B.  Such equations are called elliptic curves and they have important applications in cryptography among many other areas of mathematics.  We are interested in solving this equation in rational numbers x and y.  For some choices of A and B there might be no solution at all, like for A=B=2; for some only finitely many, like when A=1 and B=2; but quite often there are infinitely many, like in the case A=B=1.  It is hard to predict or calculate for a given A and B in which case we are.  In the infinite case, we can refine the question and count the number N(T) of solutions (x,y) such that both numerators and denominators are between -T and T for a given number T. The new formulation of the conjecture now compares this counting function to the number of solutions of this equation "modulo p" for prime numbers p below T.   Essentially, this means that we are looking for x and y between 0 and p-1 such that y2 and x3+A x+B have the same remainder when dividing by p. The usual formulation of the conjecture involves difficult analytic functions and intricate arithmetic terms like the mysterious Tate-Shafarevich group.  The new version is simpler to state and has a more geometric flavour.  But beyond the fact that the reformulation drops the level of difficulty of the mathematical objects involved, there is also hope that one can use it to change the way mathematicians look at it.   One hope is to find somewhere a patch of finite area containing the points counted by the function N(T).  It will not be a patch in the usual plane, but instead in the plane of adèles, a mathematical construction invented to bring tools from mathematical analysis into number theory.

UKRI Gateway to Research · FY 2025 · 2025-03

This follow-on project applies approaches, findings and outputs developed as part of the AHRC-funded project Coronavirus Discourses: Linguistic Evidence for Effective Public Health Messaging to enhance a London-wide immunisation campaign ('Why vaccinate?') developed by UKHSA, NHS England, Association of Directors of Public Health, Office for Health Improvement and Disparities, London Local Authorities, and community outreach organisations. Coronavirus Discourses responded to the need to tailor health communications to cater for a diverse audience in an information environment that was constantly changing as the pandemic progressed. We produced a guide for health communications professionals containing insights into public preferences for sources of health information, the effectiveness of different messaging types and framing of instructions, and understanding of language used in Covid-19 communications. By understanding these preferences, message writers may improve the reception of health communications and increase compliance with guidance. We now have the opportunity to enhance the value and benefit of the Coronavirus Discourses project by taking its insights in the new, broader direction of vaccine hesitancy. We have been approached by UKHSA, one of our original partners, to apply the learnings from Coronavirus Discourses to their new pan-London, multi-agency campaign 'Why Vaccinate?' (2024-2027). Immunisation uptake has been identified as an urgent global health priority by the World Health Organisation, and the 'Why Vaccinate?' campaign has been designed to improve vaccine uptake and address hesitancy in London, a region with a highly mobile population and social inequalities. We will apply the approaches and insights developed during the Coronavirus Discourses project to the new context of health messaging on vaccination against common infectious diseases, which will allow us to: (i) appraise and inform message design; (ii) design a blueprint for public health messaging best practice around vaccination; (iii) develop training materials to support tailoring of health campaigns for diverse audiences and deliver training workshops to partners; (iv) develop a collection of discourses around vaccination, focusing on multicultural and multilingual communities, to support public health agencies. We will achieve this through the following programme of activities: Applying the Coronavirus Discourses findings and approaches to immunisation communications in multicultural and multilingual contexts Informing a series of campaign design iterations based on audience feedback to be applied throughout the campaign's duration (2024-2027), beyond this follow-on project Adapting guidance produced as part of Coronavirus Discourses for health crisis communication for specific immunisation contexts in consultation with UKHSA Sharing the refined guidance for vaccination messaging with key stakeholders in public health communications (e.g., government agencies, health communication organisations) The assets developed for this project will be open access for any public health agency, organisation, or professional to use, and will have value for wider immunisation campaign communications beyond London. The ability to apply our research to this important campaign will illustrate the leading role of arts and humanities approaches to inform public health practice by reducing the gap between the language traditionally used by message designers and the linguistic needs and preferences of different audiences, thus improving shared understanding and decision making.

UKRI Gateway to Research · FY 2025 · 2025-03

Summary Context: This research will be conducted during the first 18 months of the new Labour government term. During the 2024 election immigration control was a key issue for the UK political agenda. This project will examine the issue of 'tied' visas that bind migrant workers or partner/spouses to designated households. We will explore the extent to which tied visas facilitate abuse as victims are dependent on their employers or spouse/partner for their legal immigration status. We will partner with the NGO the Gabriela Safehaven Southeast and East Asian Women's Association (SEEAWA). SEEAWA will function as a partner and subcontractor for this project. Challenge: To investigate the extent to which Filipino women, who have escaped from abusive traffickers, spouses and employers, end up as undocumented ‘illegals’ that are presented as a problem for UK society. This project aims to test the extent to which this situation contradicts other UK laws that work to stop comparable abuses, such as honour-based abuse and/or domestic abuse. We hypothesise that the tied-visa system compromises UK laws designed to protect the fundamental rights of women. This issue is challenging because it is legally and politically contentious. Aims and Objective: The overall research objective of this project is to examine the experience of SEEAWA service providers and UK-based service users. We aim to show how these experiences could inform future policy amendments that better protect fundamental women's rights. We will: Gather primary evidence of women’s lived experience of abuse and escape. Gather evidence of their experience of the law and how far the law has protected or undermined them. This approach will amplify a plurality of voices following the EDI aims and objectives of the AHRC. Identify all the services being provided by SEEAWA. Gather evidence on legal and political cases and developments that have addressed the legal standing of abused women migrants whose visa status is tied to abusive households. Co-develop with SEEAWA and other service providers and users tools to improve protection under the law for abused and trafficked women.  Identify the roadblocks to meaningful legal change. Outline how the contradictions between the law on immigrants and the laws on domestic violence have been experienced since the start of the UK Home Office hostile environment policies under the leadership of Home Secretary Theresa May in 2012. Identify which politicians and political parties are acting on these issues and how we can engage with them. Potential Application and Benefits: The impact of the project will be to determine the extent to which these women fall between gaps in the law and are denied their fundamental human rights.  Our work will benefit policymakers as we will create a roadmap to protect fundamental migrant women's rights. It will also benefit migrant women as a source of information and support. The project could benefit businesses, such as the healthcare sector, that are currently struggling to recruit legal migrant staff, with the skills these women currently have or could be trained in. 

UKRI Gateway to Research · FY 2025 · 2025-03

How do ecotypes develop and maintain a coherent identity on the way to becoming species? We are surrounded by many, identifiably different, species, each having some coherent set of properties that distinguish them from related species. Yet it is difficult to understand how these properties come to be associated with each other in the early stages of speciation. In a landmark paper, Felsenstein (1981) highlighted two defining properties of species: adaptations to their environments and a tendency to mate with others in the same species (assortative mating). Felsenstein went on to show that it is not difficult to explain how either of these properties alone are shaped by natural selection, but a fundamental problem is to discover how the genes underlying environmental adaptation and assortative mating become associated with one another in the genomes of diverging taxa. This must take place for coherent new species to emerge but is opposed by the genetic reshuffling (recombination) that occurs between generations in sexual species and breaks apart genetic associations ("linkage disequilibrium"). How can these associations be maintained? The answer must involve selection that favours the associations, but progress in understanding how has been inhibited by limited study of the major sources of selection and when they act during the life cycle. For many years Felsenstein's paper was largely overlooked because for most species we lacked the necessary genetic resolution to test his theory by identifying the genes that define species. Recent developments in genomic technology have reduced this difficulty. Cutting edge studies of ecotypes, local variants within species that maintain their identities through time and space, show that some genes underlying environmental adaptation and assortative mating are held together in "structural variants", genomic regions where recombination is prevented (eg "inversions", where the direction of the DNA is reversed). However, these studies cannot yet explain how such regions originate, or are held together across the whole genome with other such regions, to form the genetic associations that define ecotypes. In animals, ecotypes often differ in migratory behaviour (e.g. one ecotype migrates but another does not). The physiological demands of migration could be an important source of selection that drives a wedge between populations and allows the accumulation of suites of associated traits to suit different migration strategies. The three-spined stickleback is a common, widely distributed and genome-sequenced fish that provides an excellent model to quantify the differences between ecotypes and carry out ambitious experiments to understand how these differences might be maintained by the selection caused by variation in migration. In the North Atlantic, migratory and resident stickleback ecotypes breed alongside each other in many locations, yet the differences between them are maintained by some combination of assortative mating and natural selection, likely due to differences in migratory behaviour. We will quantify the genomic differences between the ecotypes, using state-of-the-art approaches, and investigate how these genes contribute to the adaptive differences between ecotypes in assortative mating and migratory behaviour. We will go on to use a novel and ambitious programme of experiments to understand how selection shapes and maintains the differences between the ecotypes. We will weave together the different strands of our work to shed new light on the fundamental problem of how nascent differences between taxa are maintained at the earliest stages of divergence, advancing our fundamental understanding of biodiversity.

UKRI Gateway to Research · FY 2025 · 2025-03

Brain disorders represent the biggest challenge for 21st century healthcare. 14.7M people in the UK live with a neurological condition whilst around 10M Canadians have a neurological or psychiatric disorder. These problems come at a significant cost: brain disorders cost the UK ~£100 billion per year; mental health issues alone cost Canada ~$50 billion per year. A barrier to effective management of brain disorders is the lack of technologies to objectively assess brain health. Whilst techniques like MRI have revolutionised diagnosis of disorders relating to structural abnormalities (e.g. tumours), for many conditions the underlying pathology relates to function - meaning either a change in brain chemistry (i.e. the chemicals that control electrical activity in cells) or the electrical activity itself. These are harder to measure and much of what we understand comes from research involving animals. Whilst it is possible to measure brain electrophysiology in humans (and to use these methods to infer underlying neurochemistry), the gold-standard is to place electrodes in the brain, which is highly invasive. Non-invasive techniques exist, which rely on measuring either electrical signals from the scalp surface (EEG) or magnetic fields generated by neural currents (MEG). EEG is limited in spatial resolution and sensitivity, particularly to ‘high-frequency’ signals which are markers of healthy brain function. MEG is more robust and has good spatial precision, yet classic MEG instrumentation lacks sensitivity and practicality, with scanners being costly and not well suited to many patient groups, particularly infants. Quantum sensors promise game-changing advancements in the assessment of human brain function. Quantum enabled magnetic field sensors – called OPMs – can lift the restrictions surrounding MEG recordings and recent simulations suggest that an appropriately constructed OPM-MEG device could even rival invasive measures of brain function in terms of sensitivity. This dramatic increase in sensitivity also comes at a low cost. In addition, OPM-MEG devices are much more practical, adapting to scan anyone (even babies) and enabling free movement whilst scanning. This could prove disruptive in the quest for cheap, accurate and non-invasive assessment of brain health. Here, our vision is to develop a quantum sensor-based imaging system for biophysical modelling of brain data. Specifically, our system will enable measurements of brain electrophysiology with a precision and sensitivity that has never previously been possible using non-invasive imaging. This, in turn, will permit mathematical models of brain circuits to be fitted to the data, elucidating the neuro-chemical pathways that underly the electrical function. Enabling this key advance will allow us to track how our brains change, for example over time, or following treatment. In our programme we will build the first quantum enabled scanner tailored to biophysical modelling and develop algorithms to exploit this increased sensitivity. We will test our new system in two ways: First, we will undertake a neuropharmacological study – exploring how brain chemistry and electrophysiology change with alcohol administration. Second, we will measure how brain networks alter with maturation, across the intense developmental period of adolescence. These studies will prove the principle, and the value, of biophysical modelling. Moreover, they will exploit the unique capabilities of quantum sensors for monitoring brain health. Ultimately, this will be transformative in human neuroscience and the technology we develop will find use in drug development, improving success rates in clinical trials, and moving the needle on precision medicine.

UKRI Gateway to Research · FY 2025 · 2025-03

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

UKRI Gateway to Research · FY 2025 · 2025-03

Brain tumours are the main cause of death in children and young people (CYP) under the age of 40 years. A significant proportion (30-50%) of paediatric high-grade (malignant) tumours relapse or reoccur within two years with the vast majority coming back in the same area despite evidence of a complete response on MRI scans. This suggests that there is minimal residual disease (MRD) present at the end of treatment. Finding better ways of detecting MRD could help identify patients who require additional treatment or continuation chemotherapy beyond standard-of-care (SOC), to reduce the risk of relapse. We also need to have a more sensitive method of detecting relapse early so that further treatments may be possible and effective. We know that tumour cells alter their metabolism to help them survive and evade the body's immune response. Metabolomics is the study or analysis of all the metabolites produced as a result of cellular processes. We have developed a novel metabolomics-based assay using cerebrospinal fluid (CSF) collected as part of SOC, to identify key metabolites that are specific to tumours. Thus far we have focused on two highly malignant tumours in children and young people called medulloblastoma (MB) and ependymoma (EPN). We have identified eighteen metabolites in CSF taken 14 days after surgery in tumour-specific levels, and sixteen of these metabolites are reliable biomarkers in patients (reproducible and clinically relevant). The current  NHS SOC test involves collecting CSF at the same time point (day 14) and testing for the presence of tumour cells; this test is only positive in a small minority of patients who don't have other evidence of disease spread or metastasis. We can detect metabolomic signatures in patients whose cytology is negative. We know that the key metabolites that we identify correlate with that expressed in tumours in EPN and these also broadly correlate with MRI spectroscopy data.There is also published evidence of the role of the pathways involved in synthesising these metabolites in MB and EPN. It is important to note that we have some disease-specific metabolites that distinguish MB from EPN, but we also have common metabolites that are different from patients who don't have brain tumours but are broadly similar between MB and EPN. This is particularly exciting as we propose that these common metabolites could have greater value in detecting MRD across different brain tumour types. We are seeking funding through the MRC Developmental Pathway Gap Fund (DPGF) fund to expand this work across EPN and MB to validate our results. compare samples taken from the same patient at different time intervals to see if the metabolites fluctuate with disease burden. We have some pilot work ongoing at the moment which suggests it is conserved at relapse. identify tumour-specific metabolomic signatures for other types of brain tumours where CSF analysis is currently done as standard of care. characterise the CSF proteins mediating the production of these metabolites. This step aims to see if we can develop an immunoassay- based test for MRD using CSF for several tumour types which could be implemented easily within the NHS. It is anticipated that successful DPGF funding will help us achieve the above-listed objectives in readiness for a future developmental pathway funding scheme (DPFS) application to translate this work into a clinically validated test.  

UKRI Gateway to Research · FY 2025 · 2025-03

The poor mental health of university students constitutes a contemporary global crisis. Black students’ mental health is particularly at risk due to institutional processes of anti-Black racism, ableism and sanism; discrimination often not addressed by theory, policy and practice. This project addresses this truly intersectional problem. We draw on Black, Mad and Disability Studies to explore and enhance the mental health of Black students in four English universities. We will work with Black students, academics, and professional service colleagues. First, we will identify responsive theories, concepts, and resources through intersectional conversations between and across Black, Mad and Disability Studies. Second, we will explore Black students’ experiences and aspirations of mental health support across four universities in England. Third, we will develop innovative methodologies that provide opportunities for Black students, universities, and non-academic organisations to collate and share enabling practice. Fourth, we will identify examples of enabling practice currently existing in the university that can be shared across institutions. Finally, we will raise public debate about the mental health experiences and aspirations of Black university students. Our work will inform the university, research, and third sectors to promote Black, Mad and Disabled Lives in the academy.

UKRI Gateway to Research · FY 2025 · 2025-02

The transition to net zero carbon emissions by 2050 requires an acceleration of advances in fundamental science that will have a pragmatic impact on critical technologies. The high level of research on hydrogen materials for hydrogen storage over the last decades has led to significant breakthroughs in fundamental science. Climate change now calls for a re-focus of the hydrogen material science to translate the properties of these materials toward superior and pragmatic solutions needed beyond just storage to across the hydrogen supply chains. Light transport decarbonization can be tackled through electrification, but hydrogen remains an option to decarbonize the hard-to-abate sectors such as heavy-duty transport, off road vehicles, marine and aerospace. However, implementing hydrogen as a clean energy vector has challenges in other related technologies such as compression, sensing, purification, storage and distribution of hydrogen. In this project, we focus on the challenges associated with hydrogen compression. Due to its low density, hydrogen compression is required along the entire supply chain from production to end use. A wide range of hydrogen compression technologies have been investigated, and the most common hydrogen compressors on the market are based on mechanical compression, such as reciprocating, diaphragm, linear, and ionic liquid compressors, which are costly to purchase upfront and consume high levels of electricity to run, typically requiring 20-30% of the calorific value of the hydrogen to compress hydrogen to high pressures to 700 bar and beyond. The operating cost of mechanical hydrogen compressors is high due to the requirements of constant and significant maintenance, particularly for valves, packing, and piston rings. The potential for an alternative technology such as metal hydride compressors is significant offering opportunities for compressing hydrogen using waste heat from electrolysers or other renewable sources (e.g. solar thermal) delivering high efficiency.  Metal hydride compressors do not require moving parts in the compression process, and have, therefore, much lower operational cost and significantly enhanced reliability and safety. The vision of this joint UK-Japan project is to address challenges associated with one of the main bottlenecks of developing efficient metal-hydride hydrogen compressors, i.e. identifying the optimal metal hydride materials for hydrogen compression that can be used with sustainable heat. This will be accelerated by a combined experimental-computational approach as well as the combination of the research expertises and facilities on hydrogen storage materials of the University of Nottingham and the AIST Tsukuba supported by the ICMPE (Paris) and the Sandia National Laboratory. By this approach we will be able to identify optimal metal alloy compositions that can be utilised to compress hydrogen gas from 20~30 bar (produced by an electrolyser using renewable energy sources such as wind and solar) to high pressures, e.g. > 700 bar  for hydrogen refuellers via multiple hydride combinations, or 80 bar for hydrogen pipelines via a single stage metal-hydride compressor. As experimental data is very limited and in parts very difficult to obtain, to accelerate the metal alloys discovery, we need to combine a wide range of experimental and computational techniques, including atomistic materials modelling, materials synthesis, and materials structure and hydrogen storage property characterisations using a one of a kind high pressure Sieverts apparatus. The best candidate metal alloys on hydrogen compression applications will be scaled up and tested in our in-house multi-stage prototype metal-hydride compressor device.

UKRI Gateway to Research · FY 2025 · 2025-02

Osteoarthritis (OA) affects ~10million adults in the UK, damaging multiple inter-connecting joint tissues. Inflammation of the joint lining (synovium), which contains nerves that detect painful signals, involves substances which promote swelling and pain, and other substances which inhibit these processes to allow healing. Our research is focused on a group of molecules (EETs) that reduce inflammation and pain. We showed that people with lower levels of EETs and higher levels of the inactive metabolites (DHETs) have more severe OA pain and greater progression of OA joint damage. EETs are metabolised by the enzyme soluble epoxide hydrolase (sEH). We found that levels of this enzyme in the synovium are higher in people with painful OA, and we have linked small genetic differences (variants) in the gene (EPHX2) for sEH to the amount of OA pain people experience. Hypothesis: the effectiveness of sEH in breaking-down the beneficial EET molecules into their inactive metabolites contributes to the amount of OA pain people experience, providing an opportunity for new targeted treatments. Here, we will determine the cellular processes by which knee joint sEH contributes to OA inflammation and pain, and demonstrate the analgesic properties and therapeutic potential of directly and locally inhibiting this enzyme. Project Outcomes will be delivered by 3 Objectives (Objs): Obj. 1: In 120 people undergoing knee surgery for OA pain, we will determine the relationship between sEH expression and activity in the synovium and pain (assessed by validated questionnaires and nurse-led testing). The presence of known pain-related EPHX2 variants in the synovium will be tested. Relationships between levels of EETs/DHETs in plasma and synovial fluid, and their associations with pain and sEH activity, will be established. In pre-collected knee surgery synovium, relationships between sEH expression and activity and OA joint inflammation scores will be analyzed, and sEH localization to cell populations in the synovium determined. Obj. 2: Using human derived cells and gene editing technology, the effects of an OA-relevant inflammatory stimulus and EPHX2 variants on the ability of sEH to break-down EETs and modulate the responses of inflammatory-regulating cells (fibroblasts and macrophages) will be determined. This will establish the critical importance of sEH in the crosstalk of inflammatory processes that may contribute to OA pain. Obj. 3: The role of sEH in regulating the signals that communicate pro- or anti-inflammatory messages between inflammatory cells and how these can impact sensory neuron function will be studied. To maximize the translational potential of our findings we will use a clinically relevant mouse model of OA pain, to test the effects of pharmacological inhibition of knee joint sEH on established OA pain behaviour responses and levels of EETs/DHETs. Project outcomes will provide new clinical knowledge and mechanistic insight into how sEH regulates inflammation and pain signaling to support future development of new treatments for OA pain. Outcomes will benefit academics studying mechanisms of inflammatory signalling, pathological cellular interactions in pain and other chronic inflammatory diseases linked to sEH function (Alzheimer's disease, kidney and cardiovascular disease, stroke). Outcomes for the pharmaceutical sector include new knowledge to support the development of novel efficacious treatments, which have less side effect risk. Outcomes will be disseminated via our existing national clinical networks, the Pain Centre Versus Arthritis and the UKRI funded Advanced Pain Discovery platform, conference presentations, publications and social media.

UKRI Gateway to Research · FY 2025 · 2025-02

This research project aims to develop advanced healthcare materials in the form of novel lipid nanoparticles (LNPs) for applications in vaccines and wider therapeutics. Although successfully developed for COVID-19 vaccines, LNPs have great potential for improvement, specifically with regards to their interaction with the immune system as well as storage stability. This project aims to optimise an existing polyethylene glycol (PEG) based LNP system, modifying PEG composition and exploring a recently proposed alternative to PEG to enable an appropriate immune response and improved storage stability. Improved storage will help to tackle inequalities faced by developing nations where LNPs cannot be effectively distributed worldwide.   Our innovative approach utilises recent methodology advances by our research team at Nottingham using OrbiSIMS analysis to simultaneously study LNP uptake in immune cells and the associated immune responses. This approach is high throughput and cost effective compared to existing as it can assess LNP uptake and cellular response simultaneously throughout a broad range of chemistries using very low cell numbers (tens of cells as opposed to hundreds of thousands). The OrbiSIMS data-sets generated with this new protocol are vast and complex and so in order to ensure they are fully utilised this research project will further expand an existing collaboration with experts in machine learning at Seikei University (Japan). This analysis will enable a correlation to be made between the LNP modifications and cellular uptake and metabolomic response. Our research will enable a new understanding in the impact of parameters such as LNP size, PEG molecular weight, concentration and the impact using the PEG alternative, polysarcosine (pSar). The ability to tailor these aspects will allow LNPs to be developed which can maximise delivery, immune response, transfection efficiency and storage stability. The interdisciplinary team combines unique experimental and data-processing capability and expertise from the UK and Japan and is well-positioned to drive innovation in LNP technology.   This international research collaboration will have global reach advancing areas of vaccine and therapeutic delivery, contributing to the development of more efficacious and stable healthcare materials for vaccine and therapeutic delivery. This work aligns with UKRI EPSRC's priorities impacting multiple research themes, including physical sciences and healthcare technologies. Benefits will be realised in numerous fields such as medicine, materials science, biotechnology, biology and pharmaceutics. The research supports the UKRI's strategic theme of 'Securing better health, ageing, and wellbeing' and the United Nations Goal to 'Ensure healthy lives and promote well-being for all at all ages' amongst others. This research will establish a novel high throughput approach to developing advanced healthcare materials.

UKRI Gateway to Research · FY 2025 · 2025-02

Destructive lung diseases are the third largest cause of death worldwide, with chronic obstructive pulmonary disease (COPD) alone costing the NHS £1.9bn annually. COPD is characterised by destruction of the tissue that make up the air sacs (alveoli) within the lung, leading to airspace enlargement, which reduces the ability of the lung to exchange carbon dioxide and oxygen (i.e. loss of lung function). The damage or injury to the lung tissue is driven by environmental exposures, genetics and ageing. The underlying mechanisms by which injury, abnormal repairprocesses and tissue mechanics interact to cause this destruction are not well understood. This gap in understanding makes estimates of disease activity inaccurate and delays diagnosis and timely treatment. In turn, this makes clinical trials prone to failure, delaying the translation of scientific discovery to personalised care. There is therefore an urgent need for tools that help us better understand the underlying mechanisms and for new sensitive measures(biomarkers) to detect active disease, enabling early interventions to prevent lung damage and death, and facilitating rapid evaluation of new treatments. Lung tissue destruction in COPD is complex, with multiple mechanisms causing lung tissue damage. In contrast, lymphangioleiomyomatosis (LAM), another lung disease associated with tissue destruction that can cause respiratory failure and death, involves a single gene and has a well-understood progression. LAM is rare, primarily affecting younger females; however, the simpler nature of LAM allows a more straightforward starting point for interdisciplinary study of lung tissue destruction and makes it an effective model system for understanding destructive lung disease more widely. We will exploit this to develop and validate mathematical, imaging, and biological approaches for subsequent application to COPD and with broader implications for destructive lung diseases. We will use quantitative imaging, biological and clinical data of tissue injury and repair from LAM and COPD patient lungs alongside the development of mathematical and computational models to predict changes in lung structure and function. The tools developed will enable us to address the following questions: Q1. How do gene-level and cellular mechanisms underpin tissue degradation and repair, and how are they disrupted in disease? Q2. How do (sub)cellular, biochemical, and mechanical processes interact to cause airspace enlargement? Q3. How does lung tissue loss evolve over time and how is it related to lung function? Outcomes, applications, benefits: Addressing these questions through novel combinations of biological and imaging data with computational models will help establish the relationship between injury/repair processes at the genetic/cellular level and lung tissue loss, leading to eventual clinical outcomes. In particular we will understand how the balance between injury and repair is maintained in a healthy lung. We will then identify which mechanisms cause changes in lung structure and function in disease and their early biomarkers (and how they change with time). These are essential tools for detecting LAM or COPD before the damage is severe or irreversible, addressing a significant unmet need for patients suffering from these debilitating conditions. Our validated computational models will enable prediction of disease progression and a virtual platform for testing novel therapies, ultimately contributing to a digital twin of the lung that will enable clinicians to provide the appropriate treatment, to the right patient, at the right time. The complex challenges posed necessitate an integrated interdisciplinary approach, but reciprocally will also drive innovation in each discipline individually.

UKRI Gateway to Research · FY 2025 · 2025-02

Millions of medical devices are surgically implanted every year, with annual sales approaching US$500 billion worldwide. Failure of implanted devices designed to be permanent can be as high as 20%, impacting patients' quality of life and burdening health services. Glucose sensors are used by most diabetics in the UK, with fine needle electrodes to sense glucose in the outermost tissue - they have recommended lifetimes of only 10-14 days because foreign body encapsulation renders them inaccurate, with each disposable unit costing £50. The foreign body response (FBR) is the hostile immune cell reaction of the body to implants, with chronic inflammation, infection and fibrosis being the major underlying causes of implant failure. With sustained support from Wellcome Trust and EPSRC over the last fifteen years, including a current Large Grant, we are developing novel cell-instructive polymers to reduce and ultimately eliminating medical device failure. To underpin cell-instructive polymer development, we need to be able to monitor the response of the body to novel implants in real-time. Only a snapshot of the complex biological interplay between inflammatory pathways is provided by current histological assessment of inflammatory responses measured on explants. The lack of technology to sense real-time changes of these complex processes hampers our ability to comprehensively understand these intricate inflammatory mechanisms in the hunt for polymers providing the best implant outcomes. We propose the development of a disruptive method to achieve continuous, minimally invasive monitoring of implants in both animal models and humans. Longitudinal real-time measurements of signature inflammatory markers and FBR will be made possible using an innovative wireless bioelectronic approach: conductive nanoantennae will be decorated with antibodies to achieve continuous and minimally invasive electrical monitoring of cytokines and macrophages in a multiplexed fashion. This novel wireless monitoring method will allow us to assess new polymers in situ in real-time, aiding their successful development. When used in humans, sensing will allow the continuous monitoring of the body's response to the new implant and therefore faster and better therapies that will ultimately improve implant success, patient outcomes and savings for healthcare providers. It will have broader application in the clinic for a variety of conditions where (device-unrelated) fibrosis is the source of morbidity and mortality. People with diabetes suffer disproportionately from adverse implant reactions as well as chronic wounds. Through a clinical partnership with a diabetologist, we will develop an impedance sensor that does not require nanoantenna injection for earlier clinical adoption proved on glucose monitors worn by healthy volunteers. This proposal has been co-developed by our interdisciplinary and international team, integrating expertise in cell-instructive materials, immunology, analytic devices engineering, clinical application and medical device commercialisation. The scope spans EPSRC, MRC and BBSRC remits, making it challenging for a single council and review college to fully address the multifaceted expertise and methodological range assembled to tackle this unmet need. Benefits for the biomaterials and medical device fields include mechanistic understanding and acceleration of the novel device development process which will speed impact through MedTech products to improve options for clinicians. Immunologists will better understand the kinetics of the inflammatory response enabling more complete mechanistic descriptions. Reciprocal benefits for the rapidly advancing bioelectronics discipline will be through the clinical and pre-clinical examples it will deliver, along with the methodological experience that will be contained within the journal publications and patent filings.

UKRI Gateway to Research · FY 2025 · 2025-02

This demonstrator generates key new knowledge on responsible innovation and creativity when AI is used to create, document, reactivate and conserve artworks and their archives. We will analyse how we can draw on AI to reactivate, document and archive complex artworks, including artworks created through AI, how to curate the exhibition of artworks, whether through historical records or their reactivations, and preserve them for posterity. We will develop a practical intervention in archival and conservation studies informed and led by humanities research on how to use responsible AI innovation to foster creativity and make archives more resilient. More specifically, we will investigate how to enhance existing visual and hybrid media archives through the use of AI. Through three case studies, focused on dance/performance, locative media, and the use of AI in archiving complex hybrid artworks (including AI, Extended Reality (XR) and video art), we will provide a blueprint for the responsible use of AI as a creator, documenter, and conservator of artworks and will propose implementable frameworks of what constitutes responsible AI practice within this context. We will take into consideration the inclusion of all foreseeable stakeholders, including two institutions currently facing complex demands on the conservation of their collections (The National Archives and LI-MA). Building on an AI project led by Farina and funded by the BRAID Scoping programme and two AHRC-funded projects led by Giannachi on the documentation of performance and digital art (respective partners were Tate and LI-MA), we will analyse three case studies to understand: 1) what constitutes responsible use of AI in the context of the creation, documentation, reactivation and conservation of artworks and their archives by artists, libraries and national archives, museums and galleries, and cultural organisations in the private sector; 2) how this impacts the concepts of creativity, legacy creation, authenticity, trust and responsibility in this context; 3) how the use of archives as a case study can improve AI itself. We will show that using AI could resolve what are now considered insurmountable challenges for archives and museums tasked with documenting and preserving often-mutable, complex and hybrid artworks in their collections in perpetuity. We will create a framework which will be made available to leading institutions in the field to significantly advance the status quo in archival and documentation studies, enhancing our understanding of the concepts of responsibility and authority in complex ecosystems and developing the understanding of relational or distributed responsibility by testing it in practice. This project aligns closely with BRAID’s main themes of equitable, humane and inspired innovation. Our research objectives embrace inspiration in innovation; we focus on perspectives from the arts and humanities and seek to answer research questions relating to both art creation and the conservation of artworks, and their impact on the development of AI. We emphasise the importance of equitable and humane innovation in our approach. Our case studies involve marginalised stakeholders such as disabled artists and we bring in national institutions which are not usually involved in the AI development process. We create space for these actors to take centre stage in the development of frameworks for the responsible use of AI in practice and legacy creation.

UKRI Gateway to Research · FY 2025 · 2025-01

Cholangiocarcinoma (CCA) affects 3000 people in the UK each year, with a dismal prognosis: only 13% of patients survive 3 years. CCA arises in the bile duct, which is a narrow tube with a diameter of about 6mm. As the cancer grows inside, the bile duct is further narrowed and routine scans cannot confirm if the narrowing is due to inflammation or the cancer. Diagnosis relies on the microscopy of samples taken from the narrowed area, but, when narrowed or blocked, it is even harder to obtain samples. In addition, CCA tissue is spatially variable with different areas being genetically different which accounts for resistance of CCA to drug treatment. Moreover, insertion of devices for the diagnosis and mapping of the narrowed bile duct (biliary stricture) must be combined with biliary drainage (stent insertion) to reduce the risk of complications such as infections. Our vision is to bring expertise from multiple disciplines together to develop a new technology with enhanced dexterity to navigate the biliary stricture, develop capabilities for tissue molecular mapping, and create capability to deliver treatment with greater precision. This is expected to then lead to improved survival and quality of life outcomes for patients with CCA. We aim to (a) develop the first ultra-slender snake-like robot to navigate the bile duct and obtain a 3-D mapping (b) deliver nanoparticle based new treatment to the narrowed segment due to cancer and (c) correlate the mapping of the bile duct with the molecular patterns in surgically-removed patient CCA tissue. To address the combination of challenges in both diagnosis and treatment we bring together expertise from medicine, endoscopy, engineering, robotics, imaging, bioelectrics and genomics. The proposed research will be carried out in 4 interdependent work packages (WP). In WP1, a snake-like robot carrying an imaging device that can navigate to the narrowed bile duct will be developed. This will be inserted into the narrowed area of the bile duct (in CCA tissue removed from patients during standard surgical cancer treatments) and take 3D pictures. In WP2, we will create nanoparticles which will be loaded on to the stents that are usually used to open bile ducts blocked due to CCA. These nanoparticles are taken up by the cancer cells. When a wireless electrical field is generated in the vicinity, the nanoparticles stimulate the death of cancer cells. WP3 involves the clinical characterisation of patients with CCA including assessment of their cancer using different types of imaging and tests. These images will be used by WP1 to inform the design of 3D bile duct models/dummies in which we will test the snake robot. In addition, samples from the cancer will be used in WP2 laboratory experiments to assess biological properties and process of cell death in CCA cells. We will create a database and tissue bioresource to characterise variability in CCA types. We will also use CCA tissue resected during surgical treatment to evaluate devices designed and developed in WP1 and WP2. WP4 will co-ordinate and integrate activities across disciplines and WPs to maximise shared learning across the team and deliver the work proposed. This cross-disciplinary approach will provide a new understanding of CCA, innovative tools to secure an accurate diagnosis and a novel approach to its treatment, ultimately leading to dramatically improved outcomes.

UKRI Gateway to Research · FY 2025 · 2025-01

We request core equipment funding to upgrade and renew several items of multi-user underpinning research equipment that supports the day-to-day activity of a large number of researchers based at University of Nottingham (UoN). These items have been put forward on the basis that they are very heavily used and the investment will support both large numbers of users and large research grant portfolios, ensuring maximum possible benefit. The intention is to improvement the reliability and capacity of core equipment relied on for running research projects on a daily basis by our staff and students. Requested equipment upgrades are presented as four main items: an upgrade to a 400 MHz NMR instrument; a replacement Optical Sampling Engine and ELMO system; upgrades to three X-Ray Diffractometer instruments; an upgrade to a Nikon metallurgical microscope. These investments will be of particular benefit to early career researchers, PhD students, and research technical professionals, these groups being the primary users of the equipment.