University of Nottingham

UKRI Gateway to Research · FY 2025 · 2025-10

Idiopathic pulmonary fibrosis (IPF) is a devastating condition characterised by progressive fibrosis, debilitating shortness of breath, and early mortality, with a median survival of only 3-5 years from diagnosis. There are limited treatment options to slow IPF progression and improve patient outcomes and new therapies are needed. The cause of IPF is unknown. Complex interactions between genetics and environmental exposures (virus, cigarette smoking, air pollution) cause repeated damage to the alveolar epithelium and drives fibrosis in the parenchyma. Pathology throughout the lung is heterogenous, and there is an unmet need to understand the molecular mechanisms driving and defining pathology and by extension reveal novel targets for therapeutic intervention. DNA methylation (DNAm) is a reversible epigenetic modification, with exploitable therapeutic potential, at the nexus of environmental exposures and genetics. Coupled with the potential for targeting site-specific DNAm, now is the optimum time to fully characterise the lung DNA methylome, providing a step change in our understanding and tangible targets for patient benefit. DNAm is the addition and removal of methyl groups to DNA cytosine residues, by DNA methyltransferases and Ten Eleven Translocation enzymes. DNAm consists of four DNA cytosine modifications, each with a distinct role in transcriptional regulation. Most studies profiling DNAm use technologies unable to distinguish cytosine modifications, limiting understanding and translatability of disease associated findings. DNAm is dysregulated in IPF. Global decreases in DNAm occur in IPF lung tissue linked to genes involved in lung development and fibrosis. Airway macrophages, immune regulatory cells, show differential DNAm associated with lipid/glucose metabolism and IPF severity. Fibroblasts, important for lung structural integrity, have IPF-associated DNAm changes correlated with fibroblast-myofibroblast transition and resistance to apoptosis. However, validation of links between DNAm and gene expression by direct manipulation and functional response assessment are required. Understanding the role of DNA cytosine modification to the generation of IPF pathology is not feasible in tissue with developed pathology. Instead, study of a potential driver and its alteration of DNA cytosine modification is required. Air pollution contributes to lung disease, causing 7 million deaths worldwide annually. Long-term air pollution exposure increases IPF risk, and subsequent air pollution exposure increases the risk of respiratory failure, hospitalisation and mortality. Air pollutants including vehicle exhaust alter DNAm, and our data show IPF fibroblast DNAm overlaps with air pollutant driven changes. We will test the hypothesis that: Dysfunctional DNA cytosine modification contributes to distinct IPF pathology and identifies novel therapeutic targets. Objective 1: Map individual DNA cytosine modifications associated with specific radiological fibrosis in IPF lungs, linking to gene expression. Objective 2: Define the functional impact of specific IPF pathology-associated DNA cytosine modifications on gene/protein expression and cellular function. Objective 3: Define the generation of DNA cytosine modification dysfunction in IPF using air pollution (engine exhaust) as a disease driver. DeCyFir will provide the first comprehensive profiling of DNA cytosine modification in the lung, including functional impacts on cellular biology. The focus on IPF will provide a step change in our understanding of DNA cytosine modification specific targets for translation to patients. This paradigm shift will put me in the ideal position to drive subsequent studies confirming specific targets in larger populations and conducting pre-clinical programs to assess functionality of targeting central mediators with inhibitors/repurposed therapies and modifying specific DNA cytosine modifications, springboarding and solidifying my reputation in the field.

UKRI Gateway to Research · FY 2025 · 2025-09

Context Recent research on maritime connections between Britain and Atlantic Europe (including France and Iberia) during the Middle Ages, and maritime engagement in medieval Wales, hint at far greater use of seaways by a broader spectrum of people than previously appreciated. Welsh connections have been studied in detail for the early medieval period but new discoveries of later-medieval excavated and stray-find evidence have received limited attention. In addition to exchange networks mediated via ports, such as Bristol and Dublin, the evidence now hints at more direct interaction between Wales, Ireland and Atlantic Europe between c. 1000-1500 CE., both from new archaeological discoveries and textual research activities of Welsh people in Ireland, France and Iberia. Lack of research on these recent discoveries has been influenced significantly by a growing crisis in Welsh and UK archaeology caused by the retirement of many experts on medieval finds. Aims and Objectives This studentship project aims to: 1) provide new narratives of interaction between South Wales and Atlantic Europe between c. 1000-1500 CE, by identifying representative contexts of connection within medieval Britain and western Europe; 2) produce an expert on the portable material culture of medieval Wales for the academic-, museum- or commercial archaeological sectors; 3) enhance understanding of Amgueddfa Cymru (AC) medieval collections and enhance public participation in archaeological/cultural heritage through outreach/knowledge exchange events with regional (museums) and ‘citizen science’. The aims will be pursued using two case-study regions in southeast and southwest Wales, respectively. The key research questions comprise: 1) what was the true extent of coastal exchange/embarkation points beyond port-towns to assess extent of maritime engagement? 2) what was the geographic scope and scale of connections? 3) what were the contexts of connection and maritime engagement? (fishing, exchange, pilgrimage, conquest, acculturation) Portable objects (metalwork, coins, ceramics) provide the data, principally from Amgueddfa Cymru (AC) collections, augmented by targeted material from Newport, Porthcawl, Swansea, Tenby, and Scolton-Manor museums, and PAS/Heneb HER records generated by community groups and metal-detectorists. Potential Applications and Benefits Specific outputs will comprise the PhD thesis, publications, enhanced collections at Amgueddfa Cymru (AC) and Welsh regional museums, and the digital displays. It will deliver inclusivity between academia, AC, regional museums and citizen science partners, meeting the Welsh Heritage Consortium ‘everyone represented’ CDP4 research priority. The project will have supported the development of an expert finds researcher with flexible skills for a career in academia, commercial archaeology, or the museum/wider culture-heritage sector. In recognition of the debt to citizen science, there will be three outreach/knowledge exchange events, held at AC and regional museums, hosting metal-detectorists, community archaeology groups and PAS/Heneb/Cadw colleagues. A web-based platform will also host the project website and a digital display and disseminate project results to the public.  

UKRI Gateway to Research · FY 2025 · 2025-09

There is an acute and unmet need for effective antivirals for veterinary diseases. Coronaviruses cause significant disease in both companion and livestock animals, from feline infectious peritonitis virus (FIPV) in cats, infectious bronchitis virus (IBV) in poultry, and transmissible gastroenteritis virus (TGEV) in pigs. These viral diseases significantly impact animal welfare and, in livestock animals, productivity. Antivirals may be used in lieu of a vaccine or to complement existing vaccination strategies where there may be inadequate efficacy with available vaccines. Our host-centric antivirals trigger multiple innate immune responses that target a virus at multiple steps of its life cycle. Their advantages over virus-directed antivirals are (i) their ability to inhibit multiple viruses (broad-spectrum), thus enabling versatility of deployment and (ii) the apparent lack of active selection for virus resistance. Inspired by natural compound thapsigargin (TG), we have generated a compound library of semi-synthetic antivirals with a range of antiviral activities.  These have been screened for activity against viruses of significance in human medicine, including influenza virus, SARS-CoV-2 and respiratory syncytial virus. We have identified a subset of compounds, novel tetrahydrofuran (THF) compounds, with vastly improved drug-like characteristics and improved safety profiles. Our project goal is to expand their application into veterinary medicine, enhancing their impact and commercial significance. We hypothesise that several candidates of our novel THF series of antivirals are highly effective against animal coronaviruses, demonstrated by in vitro, in ovo, and in vivo models, possess strong safety and drug-like profiles, and do not promote virus resistance. Thus, we will develop promising lead compounds based on antiviral efficacy against different animal coronaviruses, and characterise their toxicity/safety and drug-like profiles to pave the way towards clinical use against coronavirus infection in companion and production animals. Aim 1: To identify strong antiviral candidates from the novel THF series against a spectrum of coronaviruses from different animal species. Objective 1.1. Screen THF antivirals against TGE virus in vitro. Objective 1.2. Screen THF antivirals against IBV in ovo. Aim 2: To determine in vitro drug metabolism and pharmacokinetics (DMPK) properties of selected THF antivirals, and to assess the in vivo pharmacokinetics (PKs) and tolerability of selected candidates, resulting in the shortlisting of 1-2 most promising lead antiviral compounds. Objective 2.1. Screen in vitro DMPK properties of THF antivirals to assess drug-ability. Objective 2.2. Conduct in vivo pharmacokinetics (PK) of selected antiviral candidates in mice. Objective 2.3. Perform in vivo dose range-finding study of  1-2 most promising antiviral candidates in mice. Aim 3: To demonstrate antiviral efficacy of 1-2 highly promising antiviral candidates in vitro, in ovo and in vivo. Objective 3.1. Characterise in vitro and in ovo antiviral activity against FIPV, IBV and TGEV. Objective 3.2. Determine in vivo efficacy of up to two lead THF antivirals in mice against model coronavirus MHV-A59. In summary, we seek to develop our novel semi-synthetic THF antivirals for use in the treatment of coronavirus infection in companion and production animals. The making of bespoke veterinary antivirals against coronavirus infections, with the added prospect of broad-spectrum antiviral applicability, will be unprecedented in veterinary medicine and can have profound impact on the promotion of animal health and welfare. Effective treatment and shorter recovery time of infected animals will save animal lives, improve animal wellbeing, and, for production animals, reduce economic losses from infections that hitherto are untreatable.

UKRI Gateway to Research · FY 2025 · 2025-09

During the first three Observing Runs, the LIGO-Virgo-KAGRA (LVK) network of gravitational wave detectors observed 90 signals from pairs of black holes and compact stars spiraling into each other and eventually coalescing. The Fourth Observing Run is ongoing and the Fifth is expected to follow in 2027. Every run follows an upgrade that allows the LVK to "see" further into the universe and further into the past, drastically increasing the number of observed events. More sensitive ground-based detectors and a space-borne detector are expected to start operating in the 2030s and continue this trend. Several research communities, including astrophysics, cosmology, and theoretical physics, are already considering gravitational waves as one of the main discovery probes in their search for new physics.  Satisfying their needs and harnessing the full discovery potential of current and future observations requires faster data analysis methods, more accurate parameter estimation, and high-precision modelling of the new physics one hopes to discover. Our programme is designed to push the boundaries of all three of these frontiers. We will develop machine learning methods and our code DINGO for fast parameter estimation that is more accurate than existing methods. We will introduce a new approach for parametrising deviations from the predictions of general relativity in the inspiral phase, which will enable the LVK to efficiently and consistently combine multiple signals to test general relativity. We will also employ powerful numerical simulations to model gravitational wave signals that include such deviations and use them to benchmark our parametrization and calibrate waveform models. Finally, we will train DINGO to search for astrophysical environments and for new fundamental physics in gravitational wave data. Our goal is to maximise LVK capacity to discover new physics, broaden its exploitation potential and its science community, and set the stage for the exciting era of gravitational wave astronomy with the next generation of detectors.

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

The Vindolanda tablets are an unrivalled documentary source for the Roman army and its activities in Britannia. The research will examine if Generative Artificial Intelligence (AI) can support the recovery of the handwritten Latin texts and in turn how this might be applied to aid the decipherment of other similar objects across the British Museum collections. Although much work has been carried out on the tablets, numerous texts are not deciphered, and the work to recover them is painstaking. A quarter of a century ago, research was undertaken to see if computers might help (Terras 2006 Image to Interpretation: An Intelligent System to Aid Historians in Reading the Vindolanda Texts), but the disproportionate effort required did not encourage development. Now massively increased computing power and the success of Generative AI in various ancient world applications (Sommerschield et al. 2023 ‘Machine Learning for ancient languages: A survey’, Computational Linguistics, 49.3) mean that it is time to test the latest digital tools (e.g. GPT-4o) to undertake four main tasks: identify and recognise handwritten characters; digitally reassemble fragments; restore missing text when objects are fragmentary or text has been lost; decipher palimpsest (overlying) texts. These tasks would be undertaken using Generative AI pipelines that have already been created for Greek papyri (e.g. Swindall), oracle bones (e.g. Zhang), and cuneiform tablets (e.g. Dahl) and have the potential to bring new texts to light from the extraordinary Vindolanda collection, and to create improved models which could be applied to other BM collections.

UKRI Gateway to Research · FY 2025 · 2025-09

Dependent type theories are logical systems that enable us to formally verify theorems and certify the correctness of software. An example of a commercial application is Google's encryption used by the web browser Chrome, while computer-based proof assistants can verify modern mathematics. In recent years, new type theories have started to even serve as highly specialised languages for the study of complex mathematical disciplines. Around 2010, the research field was revolutionised by the inception of homotopy type theory, a variation that combines insights from logic, programming, and abstract homotopy theory. Inspired by this, the last decade has seen a plethora of new type theories including cubical, cartesian cubical, modal, spatial, cohesive, directed, and two-level type theory. Their relationships with each other are almost completely unknown and a success in one subfield has a priori limited consequences for other subfields, significantly hindering the progress of the research area as a whole. The project Triple-T will construct translations between type theories, unifying the efforts of different communities. This will be achieved by creating multi-level type theory, a framework that combines the advantages of individual (currently incompatible) theories and presents a radically new approach to studying correlations known as conservativity of extensions. As a side effect, it will greatly benefit the design of new type theories by determining in advance which features are needed in order to preserve certain desired properties. While the project will provide the field with powerful tools that can be applied immediately, it also has the potential for enormous long-term impact. By making it possible to combine the most useful aspects of currently incompatible systems, Triple-T will permanently speed up the development of new type theories and more advanced proof assistants, the formalisation of mathematical results, and the formal verification of software.

UKRI Gateway to Research · FY 2025 · 2025-09

The main goal of this research is to understand how reversible protein phosphorylation - a key process that switches proteins on and off - regulates sexual development of single-cell parasites belonging to the genus Plasmodium, which are the causative agent of malaria. These parasites have a complex life-cycle in mammalian hosts and the mosquito vector, and the sexual stages in the mosquito are responsible for transmission to the host. Of particular importance for this application, we have shown previously that the malaria parasite relies on two enzymes - a protein kinase called NEK4 and protein phosphatase called PPM2 - to drive an essential process in sexual reproduction called meiosis. Meiosis is an essential part of sexual reproduction that produces sex cells (e.g. sperm and egg cells) ready for fertilisation. Compared to model systems, such as humans, meiosis is highly different in the malaria parasite since it proceeds post-fertilisation in the developing zygote, a crucial stage required for transmission from the mosquito. NEK4 and PPM2 drive this process; however, the proteins they switch on and off are largely unknown, as are the functions of the proteins they target. Hence, identification of the proteins NEK4 and PPM2 regulate may uncover the key players that drive Plasmodium meiosis, and most importantly whether these could be targeted by drugs that will prevent malaria transmission. The sexual stages of the malaria parasite (i.e. meiosis stages) that infects humans are difficult to study experimentally, and therefore we will be using a rodent malaria parasite called Plasmodium berghei as a model that mimics the human parasite. Crucially, with P. berghei we can access and study the whole parasite life cycle, particularly the sexual stages in the mosquito. We also will utilise several state-of-the-art methods including proteomics, phosphoproteomics and cell biology techniques towards understanding how NEK4 and PPM2 control meiosis in the malaria parasite cell, and whether we can identify new proteins that drive its function. The main questions to be addressed are where and how these molecules work, what proteins do they target during meiosis and can we identify new functions for their targets? Overall, we aim to deliver fundamental knowledge of the meiotic processes that govern malaria development in the mosquito and potentially uncover novel therapeutic agents, and expect that the discoveries and new insights provided will be directly applicable to human malaria parasites.

UKRI Gateway to Research · FY 2025 · 2025-09

This fellowship builds upon my PhD which explored the impact of release on male life-sentenced prisoners’ identities and their experiences of returning to the community. A life sentence is the ultimate criminal sanction in England & Wales. In 2024, over 7,000 individuals were serving life sentences in England & Wales. There are three different types of life sentences in legislation but mandatory life sentences are this project’s focus. A mandatory life sentence is a court-imposed sentence for an individual convicted of murder, directing them to serve a minimum prison term –a ‘tariff’– before being considered for release by the Parole Board and subject to a life licence (Criminal Justice Act 2003). Despite most life-sentenced prisoners eventually being released from custody and returning to the community, we know strikingly little about the process of release for life-sentenced prisoners, and their experiences of re-entry after many years behind bars. Instead, studies that have examined ‘life after life imprisonment’ (Appleton, 2010; Coker and Martin, 1985) have all been cross-sectional, providing insights at a particular period in time post-release or upon recall to prison. My PhD helped to redress this imbalance by exploring the release experiences of life-sentenced prisoners longitudinally (i.e. before and after their release from prison), and in doing so generated theoretical insights which are of wider relevance to studies of imprisonment and release. Further, it provides the first account –longitudinal or otherwise– that explores post-release experiences and outcomes in England & Wales for those convicted of murder and subject to a mandatory life-sentence. My PhD focused on three areas of particular salience to these men’s release experiences, none of which had been explored previously for those released from life sentences: first, participants’ experiences of release on temporary licence and how such releases prepared them for release and re/settlement; second, the interaction between the ‘moral weight’ of murder and release trajectories, including what these men thought they deserved, their ability to move on, and their capacity to repair a morally injurious identity; and third, the function of social relations upon release and the power they hold in the re/integration process. All three of these areas were centred around the fact that these men were serving a mandatory life sentence for murder. Committing this particular offence changed the ways in which participants were seen by other people and how they saw themselves, whilst the length of time they had spent imprisoned limited their understanding of how to function in the world outside. This fellowship will enable me to publicise and disseminate my findings, making them available to a range of audiences. To do so, I will use the fellowship to finalise my monograph (with Bristol University Press), to publish two new journal articles (for Punishment & Society and the European Journal of Criminology), to write a policy briefing to assist practitioners and policy makers and present at academic conferences. Throughout the fellowship, I will conduct a pilot study for a third round of interviews. This pilot will be used to develop a research proposal for fellowships and grants which would allow me to extend this project further. The final aim of this fellowship concerns professional development which will help to establish myself as a rising researcher. Such activities include further training in methods and analysis techniques and acquiring a postgraduate teaching certification.

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

The global population is ageing rapidly due to advancements in healthcare. However, while people are living longer, many spend a greater portion of later life in poor health. One major factor contributing to this is a decline in neuromuscular function, where muscles become weaker and harder to control. This increases the risk of falls, social isolation, and reliance on healthcare services. Although we understand a great deal about how muscles change with age, we know far less about the nerves that control them. These motor nerves vary based on the tasks they perform. For example, nerves responsible for small, precise movements, like picking up a pen, may be less affected by ageing than those controlling powerful movements, like climbing stairs or recovering balance after tripping. Importantly, much of what we know about ageing nerves comes from studies focused on smaller, less affected tasks. This project aims to fill the gap in our understanding by studying how these changes impact the larger, more critical movements needed for daily life and independence. This gap in knowledge is largely due to methodological limitations. However, recent technological advancements have led to the development of new equipment capable of recording muscle and nerve activity across the full range of muscle forces, even during functional tasks like walking. These devices have been successfully tested in various animal models, and we are among the first to trial them in humans. The technology consists of a small, flexible film embedded with sensors that can be safely and securely injected into human muscles during activity. This allows us to measure how effectively motor nerves communicate with muscles, with the added advantage of recording from deeper muscle regions and during larger contractions—something that was previously impossible. The aim of this project is to use cutting-edge technology to advance our understanding of age-related adaptations in the human motor system, with a focus on exploring the full range of motor nerves involved in functional tasks. In healthy young and older males and females, we will record muscle and nerve activity across different muscle groups during various tasks. From this data, we will estimate the total number of motor nerves, assess their activation patterns, and evaluate how effectively they communicate with muscles. Full-body MRI scans will measure muscle size and quality, and this information will be combined with functional assessments such as walking and balance. Together, these insights will help us determine how motor nerve function contributes to everyday activities in older age. The successful application of this innovative technology will significantly enhance our understanding of how the human motor system adapts with age and how these changes impact everyday function. By identifying the most affected components of the motor system and the motor nerves most susceptible to ageing, this research can inform the development of more effective, targeted interventions. These may include the creation or repurposing of drugs that act directly on motor nerves to improve their function. Beyond advancing research into healthy ageing, these findings will also have broad implications for clinical conditions involving neuromuscular dysfunction, providing new avenues for treatment and rehabilitation strategies.

UKRI Gateway to Research · FY 2025 · 2025-09

This proposal seeks to revolutionise understanding of plant adaptation to altitude, by defining the molecular, genetic and physiological mechanisms that link the action of the only known plant oxygen-sensing pathway to genetic adaptation to altitude. With work described in this proposal we will describe new components and mechanisms of altitude adaptation through oxygen-sensing. The work packages of the proposal will address key knowledge gaps that will completely redefine understanding of plant genetic adaptation to altitude.  Understanding how plants are adapted to altitude is a key component of plant ecology and high-altitude agriculture and until recently there was no known mechanism for altitude adaptation in plants. We identified one mechanism that directly senses atmospheric oxygen (that decreases with altitude) in etiolated seedlings (Abbas et al Nature 2022 10.1038/s41586-022-04740-y). However, key knowledge gaps were revealed through this discovery. These include the importance of this mechanism throughout the plant life-cycle, genetic loci that control the mechanism, and the potential importance of the mechanism in agriculture and biotechnology. This project will directly address these knowledge gaps. The hypothesis of the proposal is that oxygen-sensing is a core mechanism of plant adaptation to altitude. Three work packages will address three key questions underling this hypothesis, to discover the importance of altitude adaptation through oxygen-sensing; What molecular and physiological processes do oxygen-regulated altitude adaptation target throughout plant development? What genetic loci might oxygen-regulated altitude adaptation target? How might oxygen-regulated altitude adaptation be a useful biotechnological tool for abiotic stress tolerance in crops? The proposed work is particularly timely, building on our preliminary data and our recent publication providing the first molecular mechanism for altitude adaptation (Abbas et al Nature 2022 10.1038/s41586-022-04740-y). The partners who will carry out work detailed in the proposal represent the best mix of expertise and background in the world to carry out the proposed work, including plant physiology, biochemistry, genetics, genomics, biotechnology and metabolomics. It offers the promise of providing for the first time a solved molecular and physiological understanding of altitude adaptation throughout the plant life cycle, solving an outstanding important problem in plant biology. The relevance of this mechanism is becoming increasingly important and urgent as global warming leads to displacement of crop plants and alpine species to higher altitudes. Results obtained will be of broad biological interest as the oxygen-sensing PCO/ADO N-degron pathway also exists in eukaryotic non-plant systems, including animals. The project involves inter-disciplinary experimental approaches spanning biochemistry, genetics and plant physiology, including exciting experimental approaches at a high-altitude laboratory, and will provide exceptional training opportunities for the associated staff, possible only through the proposed multidisciplinary collaborations and sub-contracts.

UKRI Gateway to Research · FY 2025 · 2025-09

We will develop a miniature imaging device to improve early cancer diagnosis in pancreatic cysts—fluid sacs that may become cancerous—leading to better patient outcomes and reducing surveillance and repeat biopsies. Every year 500,000 people worldwide including 10,000 in the UK develop pancreatic cancer, an aggressive disease with a mere 5% ten-year survival [CRUK,WCRF]. Early detection is crucial but hindered by the lack of effective screening programmes. However, some pancreatic cancers begin as cysts and so examining these holds great promise for early detection [Fischer2018]. Currently, doctors insert a long needle via the small intestine to extract cyst fluid for analysis. However, this method often misses early-stage cancers since the hallmark chemical is also produced by benign cysts. Therefore, for a definitive diagnosis, doctors use a ‘cell biopsy’ that collects cells for analysis using special tweezers [Cizginer2011]. However, this carries >10% chance of insufficient cell collection, necessitating a repeat attempt with 10% risk of potentially fatal pancreatitis [Balaban2021]. Further, cell biopsy may miss over 28% of cancers (sensitivity ranges 40-72%, depending on cyst type) partly due to inadequate sampling during biopsy [Genevay2011;Balaban2021]. Consequently, many hospitals avoid cell collection entirely. Direct visualization of cyst wall cell structures could enhance biopsy accuracy by guiding sampling to promising areas, reducing repeats and the risk of missing cancers [Genevay2011;Pitman2008]. Our commissioned health economic analysis indicates that confidently ruling out cancer in healthy patients, removing them from surveillance, could save £13-16 million in UK healthcare costs and prevent delayed treatment in over 600 patients annually. Globally, this could lead to 100,000 earlier pancreatic cancer detections and save £1-2 billion in healthcare costs. We have developed a 3mm diameter prototype imaging device that enhances cancer detection by capturing three additional imaging features. Unlike existing methods, our prototype projects an engineered light pattern onto tissue to capture absorption (lightness/darkness), scattering (surface roughness), and 3D texture using lasers [Crowley2024]. We call our device the Ultra-thin Scattering, Absorption, and Shape (U-SAS) endoscope. While each of these features individually can identify cancer in various tissues (pancreas, colon, oesophagus, skin) [Sweer2019;Angelo2017;Picot2017;Awe2020;Rex2019], no existing imaging instrument combines them in a package small enough for endoscopic use while offering the wide field-of-view required to guide biopsies [Angelo2017]. Our proposed device addresses this unmet clinical need. In this project we will develop a second-generation U-SAS endoscope suitable for clinical deployment. Specific objectives are: Improve hardware design for compactness (<0.7mm diameter to fit into 19-gauge needles used for pancreatic cyst biopsy), robustness, and manufacturability. Enhance software to produce high-quality malignancy “heat maps” over a 1cm field-of-view for guided biopsies. Conduct pre-clinical validation studies on ex vivo human pancreatic tissue. In future our device could complement emerging pancreatic cancer screening methods like blood and breath tests that may boost referrals for cyst investigation [Rhim2014;Markar2018]. In addition to improving biopsies, it could classify cysts by risk in hospitals where pancreatic cell biopsies are not routine. Further when paired with emerging cyst ablation therapies—which can avoid invasive, life-altering surgeries [Cho2024]—it could catalyse a dramatic shift in the pancreatic cancer treatment pathway, greatly improving patient survival and quality of life. Finally, the device’s small size opens possibilities for diagnosing diseases in other organs, such as the ovaries, bile duct, urethra, tear ducts, salivary glands, and even deep within the brain.

UKRI Gateway to Research · FY 2025 · 2025-08

Flash floods in urban areas are particularly dangerous extreme events, given their tragic impacts on human life and significant social and economic damage. Evacuation of citizens during these events is crucial to mitigate their impact. Effective evacuation strategies from flash floods can be developed through the understanding of the interactions among all the components of the process: the individuals, the flow, the waterborne debris and the urban environment. The impact of waterborne debris on the behaviour of individuals has not been addressed by existing studies and modelling tools. FAST aims at reducing human losses through improved evacuation strategies possible thanks to the innovative combination of physics-based, virtual reality and agent-based modelling approaches. This aim will be achieved thanks to the understanding and modelling of the complex interactions among the flow, the waterborne debris, and evacuees. To this end, FAST will develop the first computational methodology that combines reliable simulations of human behaviour and the physical aspects of flash floods, including waterborne debris, to provide the tools to improve evacuation and emergency response strategies during these events. FAST will exploit the innovative capabilities of virtual reality environments to conduct an experiment that will allow the development of an agent-based model of the evacuees' behaviour in the presence of waterborne debris using data-driven and machine learning methods. This model will be verified using a case study for which data on the flow and human behaviour will be collected. It will be made available as open-source code and combined with a hydrodynamic model capable of tracking waterborne debris to be used as a comprehensive simulation tool. This research will allow the fellow to grow as an independent interdisciplinary researcher thanks to training in novel methodologies in virtual reality and agent-based modelling applied to extreme hydrodynamic events.

UKRI Gateway to Research · FY 2025 · 2025-08

The goal of our project is to establish a consortium of renowned universities and industry partners in the field of electrical machines and additive manufacturing (AM) for a comprehensive study and solid development of new generation of electrical machines for key applications. In detail we will integrate different necessary steps for realizing our goal into an industry-doctoral network. These include multi-material (soft magnetic and non-magnetic materials) rotor, 3D-structured AM conductors, multi-material (soft magnetic and permanent magnet material) and multi-physical study of additive manufactured EMs. the objectives of our projects are: a) conceiving new concepts of electrical machines that benefit from the 3D geometrical freedom of AM, b) studying the potential and laying the foundations of multi-material additive manufacturing to enhance the EM performance, concretely increasing the power density, increasing the torque density, reducing the copper losses, reducing the iron losses, reducing the harmonic effects, c) establishing a network for educating qualified engineers with deep knowledge on both additive manufacturing processes and electrical machines to accelerate the industrial application of this technology, d) establishing a founded knowledge-based group of experts from academic and industry to represent a solid European innovation and to maintain the pioneering role of the EU in this field, e) reaching the necessary breaking-through technology in electrical machines to accelerate the technological development in related applications, f) reducing the stringent material requirements, particularly focusing on rare-earth magnets, in the light of raw materials shortages. We want to use AM to solve the current technological obstacles regarding electrical machines to accelerate the developing of electrical drives in areas such as automotive and aviation with direct impact on CO2 reduction.

UKRI Gateway to Research · FY 2025 · 2025-08

Ulcerative colitis (UC) and Crohn’s disease are chronic, relapsing inflammatory disorders of the gastrointestinal tract. These inflammatory bowel diseases (IBD) can result in debilitating physical and psychosocial symptoms for patients and affect society through loss of schooling, absenteeism, and healthcare costs. In 2019, there were approximately 4.9 million people living with IBD worldwide. Research commissioned by Crohn’s and Colitis UK and carried out at the University of Nottingham found that over 1 in 123 people are living with IBD in the UK in 2022. Lifetime costs for the NHS for treating IBD are comparable to heart disease and cancer. Patients with IBD are highly susceptible to bowel infections cause by harmful bacteria such as Clostridioides difficile. Disease-causing strains of C. difficile produce toxins which damage the gut barrier and can lead to severe inflammation of the bowel. Patients infected with C.difficile often experience more severe IBD flares with higher rates of hospitalisation, bowel damage requiring bowel resection, and death. However, management of C. difficile in IBD patients is exceptionally challenging. Moreover, the medical need for new treatments to control IBD durably and effectively remains very high. We have recently discovered that small molecules (miRNAs) found in the blood and intestine act as brakes on inflammation and are decreased in patients with recurrent C. difficile infection (CDI). These same miRNAs are also decreased in mouse models of colitis. We have shown that successful intestinal microbiota transplants or poo transplants from healthy donors to patients with C. difficile can replace these anti-inflammatory miRNAs. We found that that a specific combination of miRNAs which are carried by tiny synthetic particles called ‘nanoparticles’ can protect human intestinal cells from damage caused by microbial toxins and other inflammatory triggers. These nanoparticles act as smart carrier vehicles to deliver the therapeutic miRNAs to the desired location in the intestine by helping to protect the miRNAs from stomach acids. We believe that these miRNA-based nanoparticles may represent promising therapeutic drug candidates for both IBD and CDI by protecting the gut barrier and decreasing inflammation. miRNA-based treatments are beginning to show therapeutic promise, but currently there are no C. difficile-specific miRNA therapeutics and only one anti-inflammatory IBD microRNA-based treatment, Obefazimod, which has shown significant clinical efficacy in UC clinical trials. In this project, we aim to firstly create a panel of novel carrier nanoparticles with extremely small or ‘nanoscale’ dimensions to deliver the miRNAs to the intestinal cells. These nanoparticles which are undetectable by the human eye, will help facilitate the proficient and safe delivery of our therapeutic miRNAs to the intestine. In early screening assays, we will then evaluate the safety and ability of these to protect the gut barrier from inflammatory insults in a state-of-the-art human gut tissue models composed of intestinal and immune cell populations. miRNA treatments which show the greatest protective potential will be evaluated in clinically relevant human miniguts or ‘gut-on-a-chip’ and animal (mouse) models of IBD and CDI. Our project will also dissect the molecular mechanisms of action of these miRNA therapeutics using ground-breaking chemical analysis as well as molecular and microbial profiling methods. These analyses will help identify potential measures of effect of our miRNA-based treatments for therapeutic approval and potential ‘off-target’ or unwanted effects, which is an unmet need in RNA therapeutics development.

UKRI Gateway to Research · FY 2025 · 2025-08

Sensory dysfunctions shape how many of us experience the world. Examples include vision loss and colour-blindness, but also less well-known dysfunctions like hyperacusis, where sounds are experienced as unbearably loud, and parosmia, where familiar things smell distorted and disgusting. These conditions produce distinctive perceptual experiences - dysfunctional experiences - which are sometimes extremely different from those of normal perceivers. Sensory science, medicine, and psychology are uncovering the causes, mechanisms, and impact of sensory dysfunctions. Philosophy can make a unique contribution to understanding this phenomenon of high social relevance by applying its conceptual tools to the resulting experiences. Dysfunctional experiences, in turn, provide an opportunity for advancing philosophical theories of perception. They raise a new challenge for relationalist theories, on which perceptions are fundamentally relations of awareness to the external environment. Dysfunctional experiences seem to involve a perceptual relation to the environment; but how can they be relations to the environment, just like the experiences of normal perceivers, if they are so different in sensory and affective character? For instance, how can a parosmic subject to whom wine smells sewage-like and disgusting be in a perceptual relation to the same environment as a subject to whom wine smells berry-like and delightful? The IMPERCEPT project turns this challenge into an opportunity. The core idea is that many dysfunctional experiences fundamentally involve a perceptual connection to the environment, albeit an anomalous and altered one: they are imperfect perceptions. Relationalist theories, I hypothesise, are especially well-equipped to offer a positive account of this perceptual connection. Through a range of case studies involving different senses, I will develop a framework for understanding the perceptual, affective, and cognitive aspects of dysfunctional experiences.

UKRI Gateway to Research · FY 2025 · 2025-08

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 · 2025-08

Recent breakthroughs in neuromodulation, neuroimaging, and machine learning offer the potential for development of new treatments and optimising and personalising existing treatments to tackle neuropsychiatric conditions that have a huge personal, social, and economic impact. While many neuropsychiatric conditions are currently treated with a combination of medications and psychosocial approaches, a significant proportion of patients show poor response to treatment. For instance, one-third of patients with depression and a quarter of patients with a first episode of psychosis show poor response to existing treatments. Besides, cognitive impairments, that predict the quality of life for patients with neuropsychiatric conditions, are largely unresponsive to current treatment approaches. Furthermore, side effects from medications and reduced concordance with medications remain a significant issue. Stimulation of distinct regions of the brain (‘neuromodulation’) offers a potential route to new treatments for patients who respond poorly to current—mainly pharmaceutical—interventions or suffer from significant, sometimes intolerable, side-effects. However, the effects of neuromodulation are often inconsistent. Understanding how neuromodulation affects brain microstructure, circuits and dynamics is key for efficacious, personalised treatment to improve cognitive function. As a starting point, Nottingham University led a large-scale trial on neuromodulation interventions for medically intractable depression (Morriss et al., Nature Medicine, 2024). While this study showed significant long-term improvements after 26+ weeks, several sessions were needed and not all patients showed consistent improvements. While there is a clear clinical need to have alternative interventions such a neuromodulation, only few conditions can currently be treated, and many neuromodulation approaches are invasive (e.g. implants for Parkinson’s disease or Obsessive-Compulsive Disorder). Another aspect that limits current approaches, and an aspect we want to focus on here, is that they are open-loop. Open-loop stimulation is applying stimulation irrespective of ongoing brain activity. We already observed improved brain function after open-loop magnetic stimulation in depression patients and improved cognition after focused ultrasound stimulation for healthy participants. Closed-loop stimulation instead times pulses to coincide with specific brain activity patterns. Within this programme, we will test whether closed-loop stimulation can increase effect sizes. Such an advancement will shorten the number of sessions that are needed for clinical applications, could lead to more consistent results across individuals, and might broaden the scope of brain stimulation interventions across brain and mental health conditions. Within this MRC programme grant, we will (1) test the effect of closed-loop ultrasound or magnetic stimulation, (2) observe biological changes through EEG and magnetic resonance spectroscopy, (3) develop computational/machine learning models to predict stimulation outcomes, and (4) test cognitive and motor function improvements in patients with psychiatric (schizophrenia, bipolar disorder, depression) and neurological (tics disorder) disorders. To achieve these goals, we apply approaches from neuroimaging, brain stimulation, cognitive neuroscience, and computational neuroscience/neuroinformatics. Moreover, our team includes experts in schizophrenia, depression, and Tourette’s syndrome to support proof-of-principle pilot studies in patients. In summary, with neuromodulation we aim to achieve longer-term changes associated with improvement in difficult-to-treat symptoms, functioning and quality of life whilst reducing the frequency and severity of any adverse effects. Our programme grant will build on our previous work to shift our understanding of the effect of stimulation and how it can be developed into a personalised closed-loop intervention.

UKRI Gateway to Research · FY 2025 · 2025-07

Human African trypanosomiasis, caused by subspecies of Trypanosoma brucei, is a deadly neglected tropical disease of sub-Saharan Africa. Related diseases in cattle (caused predominantly by T. congolense and T. vivax) place an estimated ~$4 billion burden on developing economies in Africa, Asia and South America. No vaccine currently exists, and drug resistance is a known issue. As such, the function of trypanosome genes and their role in disease is of great scientific interest for understanding parasite biology, identifying virulence factors and tackling drug resistance. Typically, functional genetic studies in trypanosome research infect genetically identical single mutants into cohorts of animals and, as a result, use a large (and growing) number of experimental animals. There is great opportunity for reduction in animal usage in infection research by exploiting next-generation sequencing and organism barcoding to test pathogen gene mutant phenotypes in parallel. Building directly on on-going NC3Rs funding, we have demonstrated that replacing traditional gene-by-gene approaches with parallelisation can achieve a very substantial reduction in animal usage in trypanosome functional genetics. Our high-throughput phenotyping technology (DRiF-Seq) generates and quantitatively tracks 1000s of mutants in individual animals with greater statistical power than gene-by-gene approaches. This increases robustness and reliability, measures mutant-mutant variation and potentially achieves >100-fold reduction of animal usage for specific tests. Here we propose to accelerate the adoption of parallelisation in trypanosome research by transfer of skills in DRiF-Seq to a number of key early-adopter labs. These partner labs encompass multiple disciplines and applications (medical, veterinary, and basic biology), are trans-national, and have animal experiments that could immediately be reduced by parallelisation. They are also very well placed to encourage uptake of methods to further labs in infection biology. In this proposal, we will provide direct, hands-on training in the developers’ lab in the methods of mutant library production, processing and analysis, while also creating comprehensive protocols documentation for know-how transfer that can be followed elsewhere. This will greatly accelerate uptake of this specific reduction method in trypanosomes to maximise the 3Rs impact of on-going work, but also provides an example that should stimulate adoption of similar parallelisation approaches more widely in infection research.  

UKRI Gateway to Research · FY 2025 · 2025-07

There is a recognised lack of diversity in the NERC sciences, from the makeup of undergraduate cohorts to the recipients of its funding. The CITEES (Connecting, Inspiring, Training, and Employing Environmental Scientists) initiative aims to inspire, recruit, and retain diverse workforces in environmental sciences. By 2040, our vision is to have a NERC science talent pool that reflects the diversity of the UK population. Nottingham is one of the most deprived areas in England, with high levels of income and skills deprivation. The pilot phase of the CITEES initiative will therefore focus on Nottingham and on the themes of social mobility, geographic location, and the intersection of these with the protected characteristics of race, sex, and gender identity. The project has six main objectives: embed EDI principles in our working, collecting data to understand the current situation, identifying what skills are needed in the workforce, building strong relationships across local organisations, testing new ideas to improve diversity, and continuously assessing the effectiveness of the project. Nottingham CITEES will build on the existing networks of our Leadership Team drawn from the University of Nottingham, Nottingham Trent University, the British Geological Survey, and the Environment Agency. We will target educators and students from primary school to university with a view to improving representation. Our suggested co-produced interventions include university students acting as role models in schools, free educational afterschool clubs for younger students to learn about the environmental sciences, paid summer placements for students to gain experience in environmental sciences and encouraging girls to pursue STEM fields through the Girl Guiding movement. Nottingham faces a NERC science focus 'brain drain' where skilled graduates leave the region after completing their studies. Strengthening connections between educational institutions and regional employers can help retain this talent. To aid these connections Nottingham CITEES will conduct surveys and interviews with employers to identify skills gaps that can inform our pilot initiatives but also mitigate misconceptions about the environmental sciences as a career pathway which can impact undergraduate degree choice. The four CITEES pillars (Connecting, Inspiring, Training, and Employing) provide the framework on which we will build our vision. As a Leadership Team we will draw on our lived experience (e.g., coming from POLAR4 Quintile 1 postcodes to work in Nottingham, in the environmental sciences, as female scientists) alongside our deep commitment to our discipline in undertaking this project, and are driven to see it succeed.

UKRI Gateway to Research · FY 2025 · 2025-06

Conversation is fundamental for developing social attachments, and if the ability to converse with others breaks down, it can be devastating. Not only does conversation with others improve psychological wellbeing, it also buffers people against the ill-effects of stress and other health issues. People with hearing impairment report social isolation and loneliness as some of its most disabling outcomes, yet we know very little about how to support conversation for people that struggle. To date, most research examining listening behaviour in people with hearing loss has tested individuals using experimental tasks that strip away many of the processes involved in real conversation, such as the ability to use contextual information to make inferences, and the requirement to respond to what was said. In the first stage of my fellowship, I focused on conversation-relevant cognitive processing by investigating whether and how people with hearing impairment predict what a talker will say next, and how this affects turn taking timing. I demonstrated that people with hearing impairment show delayed prediction during speech listening (in spite of high intelligibility), and also found their turn taking (for predictable spoken stimuli) to be delayed compared to age-matched normal-hearing controls. This previously unacknowledged impact of hearing loss could compound audibility issues to make social interaction even harder. The next stage of my fellowship broadens my research to encompass alternative ways that listeners use contextual information to ease conversational speech listening. I will continue to investigate prediction (i.e., thinking ahead), and will additionally examine postdiction (i.e., retrospectively figuring out words that were missed), to develop a conceptual model of context use in adverse listening conditions. Through a series of behavioural and eye-tracking studies, I will manipulate confidence in perception and listening effort to assess their effects on prediction and postdiction individually, as well as on the relative prioritisation of these different ways of using context. A concurrent strand of applied research will investigate ways to support context use via acoustic manipulations, ultimately informing the development of hearing devices designed to benefit listening in conversation situations. This will involve assessing of the value of such manipulations for older adults with hearing loss listening to speech in conversation-type situations, and will culminate in a proof-of-concept study applying such manipulations in real time. It is only by investigating listening in a social context that we can understand relevant cognitive processes as they occur in conversation. This fellowship will culminate in a comprehensive understanding of context use in challenging conversation situations, and provide the foundation to allow better support for listeners with hearing impairment. I will continue to build on my relationships with hearing device companies to investigate the commercial relevance of my findings, and hope to ultimately transform the state-of-the-art in hearing devices to benefit the psychological wellbeing of millions.

UKRI Gateway to Research · FY 2025 · 2025-06

Elevations in circulating Branched Chain Amino Acids (BCAA) are well-established as a biomarker of obesity and act as a strong independent prognostic factor for insulin resistance and the development of Type 2 Diabetes Mellitus (T2DM). Over the last decade, BCAA catabolism has been considered to have a crucial role in the development of insulin resistance in people with obesity and T2DM. Moreover, pre-clinical work has highlighted that dietary restriction of BCAA in a diabetic rat model, improves insulin sensitivity while we and others have shown that defects in BCAA catabolism in the liver and other peripheral insulin-sensitive tissues have been shown to contribute to the pathophysiology of aberrant BCAA metabolism in states of obesity and insulin resistance. Here we propose to take a novel approach by re-purposing an already licensed and approved drug, sodium phenylbutyrate (NaPb), to reduce circulating BCAA levels as a strategy to treat T2DM. NaPb is currently used to treat rare genetic disorders of ammonia metabolism (i.e. Urea-Cycle disorder) and hyperammonaemia due to liver disease using catabolism of BCAA to sequester circulating ammonia, thereby reducing BCAA as a by-product of ammonia removal. A previous experimental study using NaPb was limited to 2 weeks which is insufficient for longer term markers of glucose and muscle metabolism as well as metabolomic outcomes. In line with duration of previous experimental studies using Very-Low-Calorie Diet in T2DM and phase-1 studies to investigate the efficacy of glucose lowering therapies, we therefore aim to undertake one of the first studies in humans charting the effects of short-term (6-weeks) administration of NaPb in the form of Pheburane vs placebo on BCAA, glucose and muscle metabolism. The latter is highly relevant given ongoing concerns regarding the effects of loss of lean muscle mass with glucose lowering strategies that incorporate weight loss. This will be a randomised double-blinded, cross-over design study. Patients will be eligible for the trial if they were 18-75years, BMI of 20-45 kg/m², relatively well-controlled T2DM (HbA1C < 86mmol/mol (10%)) and treated with oral glucose-lowering medication. Thirty-six participants will be randomly assigned to receive either Pheburane 4.8g/m²/day and placebo for 6 weeks via controlled randomization, in a cross-over study design. The formulation and dose of Pheburane has been shown in our pilot study as well as published study from our collaborators to be well tolerated, safe and associated with a significant reduction in BCAA levels by 8% (in people with T2DM) and by ~20% in people with pre-diabetes, predominantly via reductions in valine levels. Using state-of-the-art metabolic and molecular techniques which includes: hyperinsulinaemic-euglycaemic clamp (HIEC) to measure peripheral insulin resistance as the primary outcome; hepatic insulin resistance using HIEC, pancreatic beta cell function measured by hyperglycaemic clamp, the impact of NaPB on insulin and anabolic signalling pathways in muscle using immunoblotting studies, body composition (DXA), muscle architecture (ultrasound), muscle structure and function, mitochondrial function and metabolomics signatures from plasma and muscle; this study will determine mechanisms underlying the potential role of NaPb in regulating glucose and muscle metabolism in T2DM. Evidence derived from this study will form a basis for future experimental and subsequent randomised clinical study to harness the metabolic benefits of reducing circulating BCAA as an important therapeutic strategy as well as novel biochemical and molecular targets to treat the underlying pathogenic mechanism contributing to the development of T2DM and/or obesity.

UKRI Gateway to Research · FY 2025 · 2025-06

Immunotherapies promise to be the major break-through in the treatment of metastatic cancer, but effectiveness is limited to few cancer types. Metastatic neuroblastoma, breast and prostate cancer, affecting approximately 300,000 EU-27 inhabitants of all age groups in 2020, respond not or very poorly to current immunotherapies. To establish more effective immunotherapies, we need to better understand the specific tumour cell-immune host interactions at the metastatic site. The Mac4Me Doctoral Network adopts an innovative, multidisciplinary and cross-sectional approach, with a unique and dedicated research training programme to equip young researchers with scientific knowledge and transferable skills that are essential for today's great demand in both academic and non-academic sectors. Mac4Me aims to understand the tumour cell-immune host interactions at the metastatic site. with an in-depth molecular and mechanistic understanding of the immune and matrix changes induced by tumour cells. We will use innovative animal-free organ-onchip systems, that recapitulate early metastasis formation of brain, bone and liver. The retrieved knowledge from the preclinical models will be integrated in data from established clinical metastases and AI machine learning algorithms will be applied to identify new immune targets. Mac4Me will align with patients and the general public from the very beginning thereby bringing societal expectations and patient needs into the centre of the project to pave the way for new standards for shared decision making and acceptable health care solutions. Mac4Me will prepare a next generation of young scientists to start their own career as independent researchers being equipped with scientific knowledge and personal skills and integrating participatory science as a starting point to address the societal demand for more effective treatment solutions for incurable metastatic disease, such as neuroblastoma, breast and prostate cancer.

UKRI Gateway to Research · FY 2025 · 2025-06

The world energy council has highlighted energy efficiency and renewable energies as the most prominent action priorities which would deliver the highest impact and least uncertainty to the energy trilemma (security, sustainability, accessibility). The UK Govs ambitious target to deploy low-carbon resources for 95% of the energy generation by 2030, and both on and offshore wind expected to become the backbone of electricity generation, electric generator deployment will dramatically increase together with energy and CO2 emissions associated with the increased raw material usage. In addition, electric motors consume 50% of all global energy generation and this is also bound to increase as demand from cross-sectorial electrification increases to achieve the targeted 2030 CO2 emissions reductions. The systems that these motors drive are however typically very inefficient and contribute to a significant amount of energy wasted. All applications using a rotating electrical motor or generator can benefit significantly from variable (optimal) speed operation by employing a Variable Speed Drive (VSD). VSDs utilise electronic components such as Power Semiconductor devices, arranged in a Power Converter, together with control devices such as micro controllers to generate the desired Voltage and Frequency to drive the rotating machine at the desired speed. Variable speed operation yields significant energy savings since it allows the energy delivered (speed) to be tailored and adjusted exactly to the application requirement, eliminating wastage. Despite the clear advantages however, installation costs, together with complex heavy cabling which connect the VSD to the rotating machine remain the main barriers to a much more widespread uptake of VSDs in industrial applications. The physical combination of the power converter and the electric motor into one unit, in an integrated motor drive (IMD) solution, immediately eliminates many of the barriers to adoption. Expensive and bulky cabling and connectors are removed together with environmentally controlled cabinets/rooms for the power converter. This enables higher power density, lower costs of installation and intrinsically higher reliability due to lower part count. Moreover, a further reduction in energy consumption at the manufacturing stage is achieved with a significant, overall reduction in material usage. By considering a multi-disciplinary approach, this program will focus on removing the technological barriers which make fully integrated motor drives the answer to the problem of achieving, more sustainable electricity generation, more efficient and lower weight industrial and transport applications and dramatically reduced CO2 emissions for manufacture. Our ambition is to investigate and deliver innovative technological solutions that reduce energy wastage and minimise life cycle impacts: in manufacture by reducing the quantity of material used; through life by increasing electrical system efficiency and dramatically improving power to weight and power to volume ratios; at end of life by facilitating recycling through material reduction together with increased service life. Together, our innovations will result in a step increase in energy efficiency and reductions in environmental impact- accelerating the route to Net Zero and long-term sustainability.