University of Sheffield

UKRI Gateway to Research · FY 2025 · 2025-03

Motor neuron disease (ALS/MND) is a fatal progressive neurodegenerative condition affecting the motor neurons that enable movement through our muscles. Degeneration of the motor neurons causes progressive disability in walking, talking, eating, and breathing. Average life expectancy is 2-3 years from the time of symptom onset. Up to 5000 people in the UK are living with ALS/MND at any one time. Treatments to protect the motor neurons and slow down their loss are urgently needed. An expanded section of DNA in a gene called C9orf72 is the most common cause of ALS/MND underlying up to 40% of inherited cases and 10% of the total cases of ALS/MND. The C9orf72 gene expansion varies in size from patient to patient and produces 5 different toxic proteins that injure motor neurons to varying degrees, though their relative impacts are incompletely understood. The toxic proteins are termed either 'sense' or 'anti-sense' according to the direction the cellular machinery produces them from the DNA instructions. Previously two genetic therapy trials for C9orf72-MND conducted by Biogen and Wave Life Sciences targeted only the 'sense' proteins and failed to show beneficial effects. Some evidence suggests that the anti-sense proteins are especially damaging to motor neurons which could be why these trials were unsuccessful, though more research is needed to confidently link the particular protein types with disease severity. Currently only 2 of the 5 toxic proteins have been shown to be measurable in cerebrospinal fluid that bathes the brain and spinal cord, but these are two that don't correlate well with disease severity in patients. We have developed a novel therapeutic strategy that lowers all 5 toxic C9orf72 proteins, both the sense and anti-sense varieties, that stops disease progression in preclinical models of MND. Our partners in Crucible Therapeutics plan to evaluate this approach in clinical trials. In this project we will develop and optimise tests to reliably measure all 5 toxic C9orf72 proteins. The majority of clinical trials of new neuroprotective treatments for ALS/MND use the ALS functional rating scale or a single clinical functional test as the primary way to measure disease progression and see if a drug is having a beneficial effect. These measurements lack sensitivity to detect any difference at an early stage in the intervention and typically take 12 months or longer to see a significant effect. Wide variation in the natural disease progression rate between patients means that large cohorts are required to participate in trials over a prolonged timescale to evaluate potentially futile treatments. This places an undue burden on patients and risks exposure for longer than necessary to ineffective treatments that have no benefit . We plan to develop biological markers for our C9orf72 genetic therapy approach to rapidly show that the therapy reaches its intended target and confers a beneficial biological effect at an early stage of treatment in a small-scale early phase study to give confidence to progress into larger confirmatory trials for approval by the medicines regulators. Using samples donated by patients and clinical data, we aim to develop tests to reliably measure the toxic proteins produced by the C9orf72 expansion to rapidly demonstrate treatment effects and reduced motor neuron injury. These biomarkers will be transferrable to other trials targeting C9orf72, as well enabling the accelerated development of new treatments for people with C9orf72-MND.

UKRI Gateway to Research · FY 2025 · 2025-03

We need efficient, innovative and robust trial designs to swiftly evaluate new treatments for safe and effective ones to reach patients quickly. Adaptive and platform trials (APTs) are such innovative approaches that have proved their efficiency and are being used more frequently. Adaptive designs allow pre-specified changes (adaptations) to aspects of the trial to be made by analysing interim data while making validity conclusions. Such adaptations include early stopping of treatment arm(s) as soon as sufficient evidence is gathered or allocating more patients to treatments showing greater benefits. In platform trials, new treatment arms can be added to an ongoing trial that is planned with or without interim analyses. Greater flexibility and statistical efficiency come at the cost of additional operational and statistical complexities. Adding new arms and/or using interim analyses to make adaptations complicates the design, conduct, analyses, and reporting. Adaptations should be accounted for in the design and all analyses – otherwise, misleading results can be produced. Importantly, research consumers need to be confident that researchers are not changing goalposts to suit them during the trial. Timely access to high-quality statistical analysis plans (SAPs), accompanied by protocols is vital to enhance public understanding and interpretation of findings. Existing SAP guidance does not adequately cover considerations for APTs. Statistical methods in some accessible APT-SAPs are insufficiently detailed, making it difficult to interpret results, reproduce methods and results, and raising suspicions or doubts about the trustworthiness of results. This undermines public confidence in research leading to research waste. In addition, there is no guidance on proportionate trial data/information/results that can be released from an ongoing APT while preserving trial integrity. Therefore, we aim to develop consensus-driven SAP guidance for APTs that can be used by researchers when conducting interim and final analyses. Specific objectives are to: develop a consensus-driven minimum set of essential items that should be included in the SAP through a Delphi process; provide practical useful examples to maximise immediate use of the guidance, with the help of an annotated APT-SAP template, to speed up the production of a high-quality SAP. Those examples will be based on specific improvements to SAPs across disease areas. The annotated SAP template will provide guidance notes on things to consider in different sections of an APT-SAP; understand current practice and provide recommendations for good practice to researchers on release of trial information/results/data from an ongoing APT while maintaining trial integrity;   engage international multidisciplinary stakeholders in both the public and private sectors throughout the process and disseminate the research outputs to maximise the impact of the research.

UKRI Gateway to Research · FY 2025 · 2025-03

Context: High profile successes with Large Language Models (LLMs) and ChatGPT, such as performing well at many natural language processing tasks and passing some student assessments, suggest that they may be powerful enough to support many other text reviewing applications, despite recognised problems including hallucination. A key text review task is academic peer review, which is used for journal quality control and national research evaluations, as well as supporting funding, promotion, and tenure decisions. Although aspects of peer review systems (e.g., reviewer finding) are frequently automated or at least semi-automated, and research shows that AI can assist with human reviewers’ writing, it is not clear whether LLMs can help decide peer review outcome decisions and overall recommendations. Topic: This project is about the potential role of LLMs in the academic peer review decision process across different disciplines. It will investigate whether LLMs have the capabilities to support (e.g., by providing non-random judgements) or threaten (by providing plausible but meaningless reports) different forms of academic peer review judgement. Aims and objectives: This project will systematically assess the extent to which LLMs can review academic work and score it for quality, focusing on expert review for the UK Research Excellence Framework (REF) national research evaluation and academic journal peer review. It will assess the ability of ChatGPT to score journal articles for research quality and to write academic reviews to support these judgements. Two additional techniques will also be applied to improve ChatGPT’s prediction accuracy. Although the project uses artificial intelligence (AI) it does not develop it but applies existing AI to academic peer review, to understand and evaluate it. The project will also build community and provide a forum for academic peer review AI advice by creating a Generative AI in Scholarly Review International Advisory Committee (GAISRIAC). This will connect relevant researchers and other stakeholders, provide a common information point (a website that will host project resources, GAISRIAC outputs and links to other relevant resources), and create workshops and panel events at conferences. Applications and benefits: By comparing LLM-constructed academic peer review reports with human peer review reports, this project will gain insights into the complex and often opaque process of constructing peer review, such as the extent to which reports can be written by combining author-reported limitations with general world information and the nature of the additional insights brought by field specialists. Most of all, however, the project’s findings about the value of ChatGPT to support research quality assessments will allow publishers, editors, the REF team, research managers (e.g., interviewing candidates) and funders to make more informed decisions about whether to exploit ChatGPT for efficiency, completely ban it for plausible but misleading reports, or something in between. Finally, the insights will support the ability to detect reviews written by ChatGPT and other LLMs, which will help to safeguard the academic peer review process. The transfer of these insights into practice will be advised on and sped by the high profile influential steering group and the GAISRIAC initiative.

UKRI Gateway to Research · FY 2025 · 2025-03

We aim to enhance our research capabilities in the area of advanced optical diagnostics through the purchase of four key pieces of equipment: stereo-high-speed camera system, an atomic force microscope, a line-field confocal optical coherence tomography system, and an optical analysis system. These tools will support multiple research groups, fostering interdisciplinary collaboration and benefiting early-career researchers. Stereo-High-Speed Camera System The stereo-high-speed camera system will significantly improve our ability to capture extreme, short duration, events at improved spatial and temporal resolution. They will support the Blast and Impact Group by providing ultra-fast imaging to visualise transient events such as blast waves and structural deformations. This equipment will reduce the need for large-scale experiments, helping the university cut down on material usage and environmental impact. The cameras will be housed in the new Blast Diagnostics Chamber, making the university a global leader in blast and impact research and supporting the work of early-career researchers and postgraduate students. Additionally, the cameras will support £12.7 million worth of current research in areas such as structural health monitoring, rail, composites, and aerospace. Atomic Force Microscope (AFM) The purchase of a new AFM will enhance the University of Sheffield’s strong position in nanoscience and nanotechnology. The AFM will replace aging equipment and support ongoing EPSRC-funded research in nanomaterials, quantum technologies, and energy applications. The new AFM, located in the Sheffield Surface Analysis Centre, will be available as a shared resource and provide advanced imaging capabilities, including high-resolution scans and nanomechanical measurements. This equipment will foster collaboration across departments and provide vital training opportunities for PhD students and early-career researchers. Line-Field Confocal Optical Coherence Tomography (LC-OCT) System The LC-OCT system will significantly enhance the University’s dermatology and clinical research capabilities. It offers high-resolution, non-invasive imaging for studying biological samples such as skin tissue, enabling researchers to monitor skin conditions and engineered tissues. The system will be especially valuable for longitudinal studies in dermatology, allowing detailed visualisations of the skin’s cellular structures. This equipment will benefit several research groups, including the School of Clinical Dentistry and the Clinical Infection Research Group, and complement existing OCT technology by offering superior surface-level imaging. Optical Analysis System The Advanced Manufacturing Research Centre will benefit from this, supporting research into sustainable composite materials. The system will aid in the development of Fiber Reinforced Thermoplastic Tape (FRTT), an eco-friendly composite proposed for industries including aerospace and renewable energy. It will allow researchers to monitor the quality of composite materials. Evaluating sustainable polymers and fibers will enhance our contributions to lightweight, eco-friendly manufacturing technologies. Strategic Impact and Benefits The acquisition of these tools aligns with the UoS strategic foci on imaging, nanotechnology, and sustainable manufacturing. The equipment will enhance research across multiple departments, supporting existing EPSRC-funded projects and enabling new research initiatives. Early-career researchers and PhD students will benefit from access to advanced technologies, improving their training and research output. This investment will strengthen our position as a leading research institution, supporting over £20 million in current research and contributing to EPSRC priorities such as Engineering, Healthcare Technologies, and Advanced Manufacturing. The equipment will also promote environmental sustainability by reducing the carbon footprint of experiments and advancing research in sustainable materials. These tools will foster interdisciplinary collaboration, ensuring the UoS remains at the forefront of innovation in key scientific fields.

UKRI Gateway to Research · FY 2025 · 2025-02

This project aims to systematically examine human rights violations against journalists undertaken with impunity. Such violations include attacks on the life and work of journalists (e.g., direct violence; offline and online harassment; gender-based intimidation; and, psychological harm); the weaponization of the law and disinformation to silence critical media; state-led media capture to serve polarising agendas; online surveillance; and, the deliberate generation of public mistrust in journalism. As an indication of the severity of the situation, 80% of all 1448 journalist murders between 1992 and 2022 resulted in impunity, meaning that perpetrators of serious human rights violations are not held accountable (CPJ 2022). Particularly at risk of attacks with impunity are journalists covering critical public interest issues including political and corporate corruption, organised crime, human rights violations and environmental conflicts. This lack of accountability has been shown to engender a climate of fear and self-censorship amongst journalists, sometimes as the sole means of self-protection when states fail to deter or are directly complicit in attacks on journalists. In view of this perpetuated cycle of injustice, ending impunity for crimes against journalists is a priority of the international community in achieving sustainable development globally, including the promotion of peaceful, inclusive and just societies (Sustainable Development Goal 16/16.10). Problematically, critical knowledge gaps currently prevent comprehensive understanding of the underlying causes of impunity and how the phenomenon is manifest across diverse country settings, ultimately preventing effective remedial action and policy intervention. This project seeks to contribute to redressing these gaps by developing a holistic 'impunity profiler' (IP) to enable systematic mapping of civil society actors' (journalistic, legal and civil associations) experiential accounts of impunity, and practices employed to counter impunity. Based on an original conceptual, methodological and interdisciplinary approach (combining sociology, political science, journalism studies and computer science), the IP will support in-depth comparative assessment of impunity and countermeasures used across diverse country settings. It will be tested in three countries (Mexico, Indonesia and Serbia), to: (1) systematically understand the underlying political, civil and cultural causes of the societal problem of impunity for human rights violations against journalists, as an expression of state-based harm and a failure in accountable governance, and, (2) shed light on the consequences of impunity by methodically exploring how civil society communities are affected by and seek to resist impunity. Incorporating computer science methods and open data principles, the IP framework will produce a replicable method and novel data set to be translated into an online open data repository and training resource for researchers, civil society and policy actors to better assess impunity in country contexts. Participatory Action Research (PAR), as a method to incorporate perspectives of beneficiary communities, will be integral to developing an integrated approach to knowledge exchange by establishing a global Community of Practice (CoP), involving civil society, academic and policy communities, as primary collectors, holders and users of data on impunity for violations against journalists. The CoP will ensure uptake and use of the IP amongst beneficiaries and provide the project's impact platform. Impact objectives focus on building capacities, via strengthened methods of academic inquiry and civil society documentation practices, to generate higher quality public intent - or accountability-oriented - data to be utilised to empower local, regional and international advocacy and policy efforts to more effectively redress the problem of impunity for attacks on journalism.

UKRI Gateway to Research · FY 2025 · 2025-02

As you read this you are probably sitting down. When you sat down, were you concerned that the chair would fail? You likely did not even consider it as you may have sat in this same chair hundreds, if not thousands of times before. You used your empirical knowledge that this chair is safe for you to sit in. What if this was a new chair to you? If the chair was brand new, you would take comfort in the fact that the chair has been manufactured to a standard and been subject to some level of quality control. If the chair belongs to an organisation then you would expect that organisation to take responsibility if the chair failed and would have been replaced if reported by another user. Failure of the chair will, very rarely, be due to a poor design. The chair will be able to withstand any expected loads assuming that it has been manufactured correctly; however, the material that it is made from will be inherently variable and contain defects that are not always apparent at the point of a manufacturing inspection. The degree of that material variability may be slight and the defect sizing understood, but making sure that the design takes account of this variability through life (especially when the chair is mistreated) is often not considered. To some extent we are all materials engineers when we make a judgement that the chair appears to be 'sturdy' before we sit down, but we do this based on our empirical knowledge and not on the science that is available to us. Are you sure the next time you sit in the chair it won't fail? Your empirical knowledge only informs you of what happened last time not what 'will' happen in the future. The application of materials science knowledge will inform the future performance. Bridging the gap between the atomistic world of materials science that defines the best estimate of mechanical performance and the bounding estimates required in materials engineering that takes account of the variability and defects is key to improving trust in applying materials science to engineering structures. Assurance is about the trust that we place that the quality system has not failed. The chair may have been subject to a level of quality control before it left the factory, at this stage we need to have trust in the manufacturer. If the chair belongs to an individual or organisation, we trust that as responsible owners, that they would replace the chair if broken and that they have systems in place to check if the chair is broken before someone sits on it. This fellowship is about developing a similar level of trust for future high integrity or critical applications. We cannot use empirical knowledge, i.e. we don't have thousands of years of experience with building fusion reactors or producing high integrity power transmission systems for aerospace applications, so we must use science. Developing a similar level of trust in the predictive modelling capability in the application of materials science to these complex and high value systems, to the empirical knowledge we all have of our usual chair is key to unlocking the public trust in the safe performance of future critical systems.

UKRI Gateway to Research · FY 2025 · 2025-02

Artificial Intelligence is pushing forward the Industrial Revolution 4.0, which is transforming many areas of Society, including Science and Technology. Nanoscopy, a recognized pillar of the research and manufacture of Nanotechnology-based products, is among the areas that more quickly is adopting Artificial Intelligence. Machine learning algorithms are being developed and integrated in microscopes for its autonomous operation and in software toolboxes for the automatic analysis of large volumes of microscopy data. Scanning Probe Microscopy is particularly active in this integration with a special focus in the Life Sciences and Medical fields. Scanning probe microscopes powered by machine learning are expected to enable the autonomous and label-free nanoscale structural and functional (mechanical and electric) imaging of living cells and functional biomolecules in their native conditions, something never achieved in nanoscopic imaging. The objective of the SPM4.0 Doctoral Network is to train a new generation of researchers in the science and technology of autonomous Scanning Probe Microscopes powered by Artificial Intelligence for applications in the Life Science and Medical fields. The researchers of the network will acquire a state-of-the-art multidisciplinary scientific training in advanced scanning probe microscopy and machine learning and in their biological and medical applications. In addition, they will receive training on complementary and transferable skills to increase their employability perspectives and to qualify them to access to responsibility job positions in the private and public sectors. The final aim is to promote the wide adoption of SPM4.0 technologies in public and private research centers and in industrial and metrology institutions and to explore new horizons in the Life Sciences and Medical sectors regarding label-free nanoscopic cell imaging, illness diagnosis, or drug nanocarrier development, consolidating Europe as world leader.

UKRI Gateway to Research · FY 2025 · 2025-01

SHEFF BIOARCH will improve current bioarchaeology provisions at the University of Sheffield to enhance research quality and guarantee greater accessibility to our collections. Our laboratories have a special focus on the study of plant and animal remains from archaeological sites (archaeobotany and zooarchaeology) and have been at the forefront of world archaeological research for more than 50 years. This has been possible through constant renewal over the years and the RICHeS project will provide us with the opportunity to make yet another step in such a modernisation process. The project is also very timely as it will coincide with our move to the School of Biosciences following the unpopular decision to close the Department of Archaeology. The integration into the new premises will provide the opportunity to rethink our setup, which can be much facilitated by the acquisition of new resources and the development of new initiatives, summarised as follows: the employment of two part-time technicians respectively covering curational work in archaeobotany and zooarchaeology (SUPPORT) the acquisition of additional storage facilities for both collections (ACCESSIBILITY) the acquisition of new specimens for the zooarchaeology reference collection (EXPANSION) the acquisition of new technical devices for the archaeobotany collection (MODERNISATION) the setting up of online facilities and in-person workshops providing information about our collections (DISSEMINATION). A core element of our mission, which we want to emphasise further as part of SHEFF BIOARCH, is to make our collections available to the wider community of students, researchers, and enthusiasts. To do so, we will work at the local scale but also nationally and, to some extent, internationally. For this purpose, we are forming a consortium with the Fort Cumberland Laboratories of Historic England, located near Portsmouth, and the Department of Archaeology of the University of Aberdeen. By working together and forming a partnership of mutual help, we will be in a much stronger position to offer reliable, integrated and long-lasting bioarchaeology provision to research colleagues as well as the general public. The consortium will also have the added advantage of providing mutual training opportunities for our staff (mainly, but not only, the two main technicians) and students. This will also enhance a collaborative ethos, which is today much needed in our research environment. As part of the project, we will have several initiatives to open the doors of the university to the external world aiming to increase public accessibility. This will ensure that any investment associated with RICHeS will have the greatest possible return in terms of intensity of use and will be properly shared beyond our research groups. We will organise short courses, open lab days, workshops and conferences, therefore making sure that the accessibility of our facilities is sufficiently well-known. In doing so, we will have the opportunity to operate in conjunction with the Alfred Denny Museum of Natural Sciences, with which we have already started collaborating. SHEFF BIOARCH will also provide us with the opportunity to consolidate our network of work relationships with a wide range of museums, commercial archaeological units, and community groups, which can all potentially benefit from the use of our collections.

UKRI Gateway to Research · FY 2025 · 2025-01

Age-related hearing loss (ARHL) is one of the most common health conditions affecting adults, causing a progressive loss of hearing sensitivity and decreased ability to understand speech. Approximately 1 billion people worldwide will experience disabling hearing impairment by 2050 (WHO), primarily linked to ARHL, excluding them from basic day-to-day communication, which leads to social isolation and depression. Despite the impact of ARHL within our society, there are no treatments because we know very little about the underlying mechanisms. Recent research has primarily focused on the role of the sensory hair cells and their neurons in ARHL, neglecting the vital role played by the supporting cells, which are crucial for the function and survival of the cochlea. Supporting cells regulate essential physiological processes in the cochlea such as maintaining fluid homeostasis and protecting against noxious stimuli, and disrupting their activity leads to deafness. We have recently demonstrated that the expression profile of three metabotropic purinergic receptors (P2rY1, P2rY2, P2rY4) in the supporting cells changes with ageing, leading to an increase in ATP-induced Ca2+ responses and the appearance of Ca2+ oscillations. These age-related changes seem to recapitulate the purinergic receptor expression profile found in the developing cochlea, which has been implicated in the modulation of gene expression and interpreted as a signalling mechanism to sense damage to the sensory epithelium. However, evidence for the specific role of the three P2Y receptors in the cochlea is lacking and the reason for their expression changes with age is unknown. The overarching testable hypothesis is whether the "return" of purinergic receptor expression in the aged cochlea to a pre-hearing configuration is an attempt to prevent or to avoid further damage to the senescent sensory epithelium. As we begin to develop therapeutic strategies to combat ARHL, should we target the hair cells/neurons or the supporting cells? If the latter, should therapeutic interventions aim to promote or prevent the age-related changes in purinergic signalling?

UKRI Gateway to Research · FY 2025 · 2025-01

Social ties and relationships are an integral component of democratic governance (Lawson 1980; Putnam, 2000). High trust interactions between citizens and political actors such as politicians, government officials, and journalists, enable collective action, inspire participation and ensure adherence to political rules and norms. Yet these bonds are subject to challenge and increasingly frayed. Digital technology has been heralded as one way of rebuilding social ties, but evidence of polarized debate, untrustworthy information, uncivil behaviour and transient engagement challenges this idea. Building on previous work revealing citizens' preferences for frequency, form and channel of communication from those political actors (Soo et al.2020; Weinberg 2023a), we consider whether and under what conditions digital communication can strengthen or erode trust - specifically looking at communication via email, social media, chatbots, social media influencers, and AI-generated synthetic media. We expect minority communities will have different expectations for communication with political actors and will examine how women, ethnic minorities and diaspora communities respond to alternative forms of contact. Using surveys and experimental methods in Canada, France, Poland, and the UK, we examine whether and how each point of contact could be optimized to promote trust. Such analysis is vital to ensuring that trust is promoted across diverse communities and that inequalities and discrimination are not exacerbated in our political systems. Moreover, it allows us to determine whether singular modes of trustworthy communication exist, or whether potentially competing conceptions of trustworthy interaction need to be theorised. Importantly, we then ask elites and citizens about their responses to these strategies to assess viability.

UKRI Gateway to Research · FY 2025 · 2025-01

Systematic reviews are a type of literature review used by researchers to collect evidence from many different sources and summarise it in an unbiased way. However, growing research indicates that published systematic reviews may not be as reliable as they are expected to be. The purpose of this research project has been to document the growing evidence that published systematic reviews are conducted which may not be trustworthy or reliable. This has involved creating a website to help researchers to explore the many "problems" with systematic reviews and to see the variety of research articles which highlight these flaws. So far, literature searches between 2000 and 2022 identified 485 included papers which relate to 67 different problems with systematic reviews. Poorly-done systematic reviews may still be being used by clinicians and decision makers to guide patient care. Due to the vast number of papers being published about this topic, this research is currently being updated regularly to understand the emerging findings in a "living" review. The next phase of this research is to consult with experts who do systematic reviews about what problems are the most likely to affect whether a systematic review can be trusted as reliable. This transition support award allows the process of planning and consulting with experts to be done in a rigorous and fair way. It also allows for further updates of the living review to be performed, ensuring that the emerging evidence on this topic can be understood as it evolves over time. This involves exploring how research culture or the environment in which scientists operate in can contribute to the increasing problems with systematic reviews. This work aims to promote best practice in science including: 1. being open and sharing data; 2. being inclusive and thorough about what/who to include; 3. being rigorous and using the best practice methods that are available and; 4. conducting the research carefully, meaningfully and without any vested interests. These principles for best practice in science will be shared widely to shape the broader research agenda and influence positive changes in the academic research environment.

UKRI Gateway to Research · FY 2025 · 2025-01

In the brain and spinal cord, there are about 100 billion nerve cells, or neurons, that enable us to think, remember, see, hear, speak, feel... and move. Neurons talk to each other at connections called synapses. Motor neurons that control our movements connect to muscles at neuromuscular junctions. Communication between neurons and between motor neurons and muscle is called neurotransmission. Neurological conditions such as dementia or motor neuron disease start when communication at synapses or neuromuscular junctions becomes disrupted. When the communication is disrupted for too long, synapses and neuromuscular junctions break down, and finally neurons die off and are lost forever. In this project we want to investigate what causes synapses to malfunction and disappear in two related neurological diseases, namely amyotrophic lateral sclerosis (ALS), which is the most common form of motor neuron disease, and a form of dementia called frontotemporal dementia (FTD). ALS and FTD overlap genetically, pathologically, and clinically. Familial forms of both diseases can be caused by mutations in a number of genes including the TARDBP gene (encoding for TDP-43), and the C9orf72 gene. Mutations in the C9orf72 gene are the most common genetic cause of both ALS and FTD. The mechanisms behind ALS and FTD are varied and not well understood, but the symptoms of these diseases ultimately are the result of a failure in neurotransmission. Our previous research found that losing the C9orf72 protein reduces neurotransmission, which disrupts neuron activity and brain function in a manner similar to what happens in ALS/FTD patients. Similarly, defective TDP-43, which is present in nearly all ALS/FTD cases, also directly affects synapses. Evidence from our lab and others points to a specific part of the synapse called the presynapse as the main site of damage in ALS/FTD. The goal of this project is to understand how the presynapse is disrupted in ALS/FTD and how this causes the breakdown in communication between neuron that we see in patients. Discovering this could lead to new therapies.

UKRI Gateway to Research · FY 2025 · 2025-01

Life-threatening fungal infection is much less understood that bacterial and viral infection. Much less money is spent on its research and finding new treatments than for other diseases that cause similar mortality. Cryptococcal meningitis (CM) is fungal infection of the immunocompromised caused by the fungus Cryptococcus neoformans. Cryptococcal meningitis is responsible for more than a hundred of thousand deaths globally each year and 20% of AIDS related deaths. HIV causes a deficiency in immune system (immunocompromise) and most deaths from CM are in people who are HIV positive in low- and middle-income countries. Treatment of HIV in these countries is improving but because there are problems getting the right drugs for HIV, paying for them and taking them, the number of people who die from CM is not decreasing in proportion. This has been compounded by the effects of the COVID19 pandemic which has severely delayed global development goals, including treatment of HIV. Treating CM is very difficult also because people are often not found to be infected until they are very sick and the drugs for CM are toxic and expensive. In our research, we are trying to understand how immune cells can protect us from this infection. We want to use this knowledge to help treat CM and other infections in the UK and globally. We will do this by understanding how the cells of immune system remove infectious microbes by ingesting and killing them. This process is called phagocytosis and our research is focussed on immune cells called macrophages. We have discovered that macrophages have sub-micron ridges on their surface which enhances their ability to interact and phagocytose Cryptococcus. In this research we want to understand how ridges enhance the ability of macrophages to phagocytose Cryptococcus, how this happens and is affected by the environment in the lung, bloodstream and brain, and how the activation of the immune system changes ridges and their function. To understand ridges on macrophages and how they might be targeted as a new treatment for CM we are combining different research disciplines - infectious diseases, microscopy and biophysics research. By studying CM as an infectious disease we can understand what happens in human infection and what is not known that we can investigate using different experimental models. In these experimental models we are using many different types of microscopy to be able to see how microbes and macrophages interact and the result of their interaction. We are using biophysics to understand how microbes and macrophages interact. We are using these three different areas but also combining them together: for example, we will use measurements from microscopy to perform theoretical physics calculations, from these calculations we will make predictions about the interaction of macrophages and Cryptococcus which we can test in my experimental models and by analysing human disease data. To convert the knowledge we will gain from our research into new treatments, we are looking at how the immune system can be modified to take advantage of macrophage ridges. Many drugs currently used and in development modify the immune system. We will test how different sorts of immune system activation change macrophage ridges to identify if there might be new ways of treating CM.

UKRI Gateway to Research · FY 2025 · 2025-01

Disturbances in neuronal function (excitability) are considered a hallmark of MND. Abnormalities known to occur early and are considered to precipitate neuronal degeneration and generate symptoms of the disease. Excitability changes therefore represent a key therapeutic target. In vivo human neurophysiology and in vitro electrophysiology provide detailed insights into disturbances in neuronal function. While related, these two strands of MND research - in vivo and in vitro neurophysiology - have not previously been aligned. This project will join clinical neurophysiology and laboratory electrophysiology together, generating a unique platform for pharmacological screening and understanding disease pathophysiology. Leveraging our expertise in clinical neurophysiology and our track record with MND induced pluripotent stem cell (iPSC)-derived neurons, we will develop a novel high-throughput pharmacological screening assay using cutting-edge multi-electrode array electrophysiology. This will substantially accelerate drug discovery targeting electrical impairments. Whilst neuronal excitability is disturbed in MND, many patients present with heterogeneous profiles, which must be considered by therapeutic approaches. For the first time, we will generate iPSCs from MND patients with clinically-defined electrophysiological characteristics, identified through detailed testing of both central and peripheral nervous system excitability. Using our new high-throughput approach, we will link our laboratory and clinic work to establish drug screening assays on electrophysiologically stratified patient iPSC-derived neurons. As a result, the study will establish a unique platform for testing novel therapeutic agents in order to rescue neuronal function disturbances specific to individual patients. Furthermore, we will make electrophysiological stratified iPSCs available to the MND research community.

UKRI Gateway to Research · FY 2025 · 2025-01

Artificial intelligence (AI) is at the forefront of many technological innovations across nearly all sectors of modern life. However, it mainly relies on large, expensive cloud compute centres that consume considerable energy, which limits its adoption in smaller, remote devices that demand real-time processing. Neuromorphic computing is a solution to this problem, where bespoke, unconventional hardware is used to naturally perform the computational tasks in an efficient manner. Spintronic systems have considerable benefits for this paradigm. They can be manipulated with low energy cost, their state can remain unchanged for long periods of time, they exhibit complex dynamics and can be integrated into conventional electronic systems easily. Recently, spintronic systems have garnered interest in the physical reservoir computing (PRC) field. PRC is an unconventional computing paradigm aimed at using fixed systems to perform the necessary processing, reducing the training complexity and avoiding the manufacture of large scale physical neural networks. However, despite the number of successful demonstrations of spintronic reservoir devices, there are challenges in realising them as the next generation of AI computing platforms. The computational power of a single device is hard to optimise for all the competing properties of an ideal reservoir. Recent computational studies have shown that by feeding the output of one reservoir device into another creates richer properties useful for complex real-world problems. This project’s vision is that for spintronic PRC to become a revolutionary technology it must expand beyond single reservoir systems and that diversity in the component devices can be exploited to give computational power greater than the sum of its parts. These heterogeneous spintronic device networks (HSDNs) lie in a middle ground between monolithic one device reservoirs and highly distributed artificial neural networks, with each node more complex than a single neuron and diversity in how they process data. This mimics how the human brain has evolved, with specific wiring for certain elements, such as the visual pathway, working together as a complete cognitive system. Therefore, the project aims to exploit a range of spintronic reservoirs devices, “fusing” them to create complex heterogeneous networks of reservoirs where the individual components contribute different characteristics. To achieve this aim, I will use machine learning models to first learn the behaviour of a range of spintronic devices. These models will be used to first characterise the systems to understand their heterogeneity. Then they will be used as part of a training algorithm to optimise the topology and connectivity of the networks. Throughout this project there will be additional experimental research to provide a wider set of spintronic systems to learn, perform key validation of the models and to demonstrate experimentally a proof-of-principle of the heterogeneous networks. This comprehensive approach will showcase the performance of these "fused" reservoirs on cutting-edge tasks, such as human-machine interaction and multi-modal activity recognition, paving the way for a more energy-efficient and powerful era of AI computing.

UKRI Gateway to Research · FY 2025 · 2025-01

The rate of information growth corresponds to an annual increase of 19%, reaching 100 zettabytes by the end of 2022, and novel optoelectronic tools are required for fast information processing. With perpetual generation and flow of information around, increasing the bit rates of devices that process information is imperative for sustainable future. Typically, optical signals - photons - are sent over fibre links, and that is how majority of internet traffic flows. However, photons do not interact with each other, unless they couple to a medium in which they propagate. One way to act is converting light into electronic signals, and processing signals with conventional electronics. However, in this case Ohmic losses reduce energy efficiency and processing speed is defined by electronic timescales. A distinct way to process light relies on strong light-matter coupling. When photons are coupled strongly to optical transitions and particles in semiconductors, they become hybrid light-matter particles - polaritons. Polaritons acquire nonlinearity and allow for information processing in an all-optical way. The efficiency of this process largely depends on many-body properties on materials used for building optical devices. The project aims to develop a distinct family of optoelectronic devices by exploiting many-body interactions in semiconducting bilayers. Recent results show a highly nonlinear polaritonic response in systems of transition metal dichalcogenides (TMDCs) when these 2D materials are doped with excessive charge (for instance, free electrons). In bilayer geometry, they reveal a zoo of various intralayer and interlayer quasiparticles based on bound electron-hole pairs correlated with electrons. By coupling these quasiparticles to light, we expect that strong coupling merged with many-body interactions will lead to game-changing increase of polaritonic nonlinearity. However, accessing this physics requires developing new theoretical tools that can capture strong correlations in such a system. Many other properties needed for building polaritonic circuits and processing units are yet to be explored. In the project, we aim to develop a theoretical description of 2D polaritons in transition metal dichalcogenides and propose blueprints for optoelectronic devices that use polaritonic many-body interactions. Our project is structured around three objectives. 1. We will develop a theoretical description of nonlinear response in doped TMDC bilayers in order to characterise many-body interactions of 2D polaritons. 2. We will study nontrivial transport properties of doped TMDC bilayers to design polaritonic circuits based on many-body interactions. 3. We will use highly nonlinear polaritonic lattices in TMDC heterobilayers to develop polaritonic computational networks. As a result, we will develop the background for future 2D polaritonic devices based on highly nonlinear bilayer systems.

UKRI Gateway to Research · FY 2025 · 2025-01

The proposed project, “CATALYSE”, will develop, and maintain long-term collaborations between Europe, China, South Africa, and Nigeria towards renewable dimethyl ether (DME) fuel production from CO2. This objective will be achieved through joint research in new process systems and material development in direct air capture (DAC) and utilisation. This requires skills and knowledge inexperimental study, process modelling, analysis and optimisation, computational material design and catalysis which will be strengthened by the individual mobility of researchers between Europe and the participating countries. There are 14 partners involved in CATALYSE who are world-leading in their respective areas of which there are 3 industrial partners. CATALYSE will start in January 2025 for 48 months. There will be 25 experienced and 32 early-stage researchers to participate in 330 person-month exchange visits. A total of €1.52m funding is requested to support the planned exchange activities. The European partners are experts in process modelling and optimisation, process intensification, computational material design, catalysis, and CO2 utilisation while the Chinese partners are experts in process intensification, green hydrogen production and DAC. The South African partners are experts in DAC and sustainability assessments while the Nigeria partners are experts in renewable energy and green hydrogen production. Knowledge transfer and training will take place through the planned secondments. We will generate at least 30 Journal publications and 30 conference papers. In addition, 2 Special Issues will be published in leading journals such as Applied Energy, 2 Workshops and 2 Special Sessions at major international conferences will be organised to disseminate project results.

UKRI Gateway to Research · FY 2025 · 2025-01

The Global Commission on People-Centred Clean Energy Transitions recommends incorporating Gender Equality and Social Inclusion (GESI) in any efforts to advance the energy transition.[1] The Independent Expert Group on Just Transition and Development in Africa advocates for a transition based on social justice and feminist values.[2] The UN Gender and Energy Compact (under the auspices of the SDG7) identifies five outcomes for women to lead, participate in and benefit from a just, sustainable, and inclusive energy transition: increasing women’s access and control over energy resources; incorporating GESI in transition pathways, strategies and regulations; supporting women-owned and led businesses; facilitating women's career advancement in the energy transition; and enhancing the knowledge base to understand processes of exclusion.[3] However, empirical evidence shows a persistent gender and inclusion gap in the energy transition. This gap manifests in the lack of participation of women and gender non-conforming people in the sustainable energy labour force. There is limited knowledge of how gender relations and intersecting forms of social discrimination (such as racism or ableism) reproduce energy injustices in the energy transition. During the last decades, many energy projects have incorporated GESI concerns, for example, collecting gender-disaggregated data or holding single-sex learning sessions. However, such approaches fail to challenge the root causes of discrimination and social inequality. Many projects focus on differences between men and women without questioning the homogeneous, universal categories used to characterise diverse groups and complex experiences of power relations and exclusion. Over-simplifying the relationships between gender relations, discrimination, and access to energy resources leads to decontextualised, inappropriate actions (such as when cookstove improvement programmes make inaccurate assumptions about cooking practices and fuel choices). Such generalisations portray women as passive victims or virtuous stewards in ways that increase their responsibility for delivering collective action without the corresponding rewards (such as when biogas-cooking programmes seek to ‘empower’ women but inadvertently result in additional domestic labour). A GESI-transformative approach to the energy transition requires challenging these types of decisions and practices, which tend to reproduce energy injustices, whatever their intentions. JustGESI will deliver substantive action to advance GESI objectives within the energy transition in Africa, focusing on: How to advance GESI objectives within concrete projects and policy interventions. Identifying and promoting institutional and policy reforms that facilitate GESI objectives. Identifying and delivering forms of capacity building that advance transformative strategies to GESI. This interdisciplinary, international partnership will deliver practical, policy and capacity-building responses through a collaborative programme of work across four countries, Ethiopia, Malawi, Mozambique, and Tanzania, where our well-established research network has obtained evidence of inclusivity gaps in the energy transition and are already initiating pilot actions to tackle these. The project will address the Ayrton challenge of ‘smart delivery,’ delivering ‘inclusive energy & leave no one behind’ interventions by putting questions of equality, diversity and inclusion at the heart of the transition to sustainable energy. Simultaneously, the project will address the challenges of ‘super-efficient demand’ and ‘modern cooking services’ by focusing on the delivery of sustainable fuels for cooking. At COP28, world leaders committed to clean cooking for all Africans. However, despite pioneering examples of gender-responsive electric cooking programmes, there is not yet a credible international GESI strategy for clean cooking.   [1] https://www.iea.org/programmes/people-centred-clean-energy-transitions [2] https://justtransitionafrica.org/ [3] https://genderenergycompact.org/

UKRI Gateway to Research · FY 2025 · 2025-01

Multimodal Artificial Intelligence (AI), which integrates diverse data modalities such as text, image, and sound, is transforming our interaction with technology and data. A 2024 MIT Technology Review Insights article predicts the global multimodal AI market will grow at an annual rate of 32.2% from 2019 to 2030, reaching US$8.4 billion. This growth, primarily focused on multimedia data, only scratches the surface of multimodal AI's potential beyond common multimedia modalities. By leveraging diverse data sources and domain expertise holistically, multimodal AI has a crucial role to play in addressing Tomorrow’s Engineering Research Challenges (TERCs), from health and wellbeing, transportation systems, and robotics to materials discovery, space research, nature-based engineering, global engineering solutions, and responsible engineering. The 2022 EPSRC TERC report identified the above eight key challenge areas, all requiring cross-disciplinary collaborations and integrated solutions. However, current research efforts are often fragmented and siloed, with researchers from different TERC areas working within disconnected boundaries of their own disciplines. Solutions developed in one discipline face significant barriers to being transferred to other disciplines, although multimodal AI solutions often share common challenges in their development pipeline. This highlights the need for findable, accessible, interoperable, and reusable solutions to benefit multiple disciplines. Over the past two years, we have created a vibrant multimodal AI community in the UK, comprising over 200 researchers and practitioners from diverse scientific and application domains. This laid the foundation for addressing shared multimodal AI problems in TERCs collectively, productively, and sustainably. The UK Open Multimodal AI Network (UKOMAIN) aims to connect multimodal AI stakeholders and solutions across disciplines to address such problems in TERCs holistically and systematically for sustained and thriving growth. Our objectives are to: 1) To establish and expand a diverse and interdisciplinary network of researchers, industry partners, policymakers, and end users to promote collaboration and inclusivity, integrate diverse perspectives and contributions, and unleash Multimodal AI’s potential in critical TERC areas such as health and wellbeing, transportation systems, and climate change. 2) Build a knowledge exchange and collaboration platform through a streamlined governance structure, carefully designed incentives, and well-connected engagement activities to foster a continuous flow of innovative solutions and interdisciplinary research. 3) Fund small-scale, high-impact feasibility studies to address specific TERCs that share common multimodal AI challenges and develop novel engineering approaches beyond their traditional boundaries, leveraging expertise from diverse related domains and generating preliminary outcomes for larger-scale projects. 4) Engage industry and policy stakeholders to align our research with real-world needs and relevant policy initiatives that are key to deployment-centric research and potentially inform policy development. 5) Embed principles of environmental sustainability and social responsibility in network activities and funded projects to invest in our future and integrate diverse perspectives. 6) Enhance our research capabilities and outputs by leveraging research facilities and expertise across the network, providing training and upskilling opportunities and promoting open science practices. To achieve these objectives, we will establish eight thematic and three community-focused special interest groups, organise workshops, hackathons, tutorials, sandpits, and grant-writing retreats, and build open-source resources. We will fund cross-TERC feasibility studies, community-led network activities, and early career researcher development with carefully designed incentives aligning with our objectives. These and related activities will transform cross-cutting multimodal AI research towards deployment-centric and user-centric innovations addressing the multifaceted TERCs and delivering much-needed economic and social benefits.

UKRI Gateway to Research · FY 2024 · 2024-12

The EPSRC National Epitaxy Facility (NEF) seeks investment in a suite of capital items at The University of Sheffield (TUoS) and the University of Cambridge to further its mission to support world-class compound semiconductor research in the UK. Epitaxy is a crystal growth technique allowing deposition of atomically thin layers of semiconductor materials. These materials are used to create functional devices that constitute the bedrock of modern photonics and electronics at the heart of internet communications, data storage, displays, solar cells, environmental sensors, AI chips, and quantum technologies. The new equipment consists of advanced photodetectors for characterisation of materials, and equipment to increase the efficiency of Metal Organic Vapour Phase (MOVPE) reactors that produce the semiconductor wafers for the UK community in both academia and industry. The requested equipment will allow the facility to offer enhanced materials characterisation capabilities, will increase the operational efficiency of the facility including maximal use of staff time, and will offer opportunities for enhanced training of technical staff including Research Technical Professionals (RTPs). It will also support efforts to increase the pace of innovation to maintain the UK's excellent position globally in the field of compound semiconductor research and development and further UKRI missions and objectives in providing impact from publicly funded research. The NEF is the largest of EPSRC’s National Research Facilities (NRFs) whose purpose is to support research communities in the UK with access to world-class infrastructure and expertise. The NEF provides the UK with bespoke epitaxial wafers, underpinning semiconductor research across a broad range of EPSRC themes – a role it has played continuously since its inception in 1979. The facility has ISO9001-certified Quality Management and has decades of research excellence resulting in internationally-leading publications and pioneering research impacts; including technology transfer to industry and support for new start-up companies in the sector. The NEF was cited in the recently published National Semiconductor Strategy as a key element of semiconductor research in the UK. Moreover, the RAEng Quantum Infrastructure Review, commissioned by the Department for Science Innovation and Technology (DSIT) to inform the £2.5bn National Quantum Strategy Programme over the next 10 years, specifically calls for increased investment in existing national epitaxy capability to enable higher-volume production and support growth of this sector. Semiconductors and Quantum Technologies have been identified by the UK Science & Technology Framework as two out of five technologies critical to securing UK strategic advantage and to delivering prosperity, security, and sustainability for the Nation.  The pace of innovation in semiconductor science and technologies globally presents a major challenge to the UK. This new equipment will allow the NEF to increase its operational efficacy and will open up new scientific possibilities for users throughout the UK.  Managed strategically through the NEF as a centre-of-excellence,  it will enable UK researchers in academia and industry to continue play a leading role in the future of the semiconductor industry in line with mission-led national objectives.

UKRI Gateway to Research · FY 2024 · 2024-12

Humanitarian visas (HVs) are facilitated visas that allow people fleeing conflicts, persecutions and humanitarian emergencies to cross an international border safely and find physical and legal protection in another country. The academic literature is highly focused on the discretionary power of European Union countries in individually deciding about HVs and their pros and cons. However, the use of HVs in South-South corridors and its specific dynamics are still understudied. This study addresses this gap in the specific case of Latin America, where scholars have recognised how humanitarian visa policies lack a clear definition, to whom they are applied and how they impact other international protection systems, such as asylum. Most studies focus on HVs in the context of the Venezuelan displacement in the region or on individual HVs in Brazil. The country created its first HV program in 2012, later consolidated in its Migration Law in 2017. Until 2024, Brazil has granted HVs to four different groups: 1) Haitians; 2) people affected by the Syrian armed conflict; 3) Afghans and 4) Ukrainians. By looking at Brazilian stakeholders' perspectives, this study will contribute to better define humanitarian visas and evaluate related policies. This project aims to establish and consolidate a diverse and interdisciplinary network of collaborators to advance knowledge about HVs in Brazil in order to contribute to the conceptual debate and co-develop further research projects on the issue. We aim to answer the questions: How do different stakeholders perceive and evaluate Brazil's humanitarian visa (HV) policy? What can other countries learn from that? The core network will involve three Brazilian early career scholars working in Brazil and the United Kingdom. Through two project visits (one in Brazil and one in the UK), we will develop and consolidate a network with different stakeholders: Brazilian and international scholars (especially from the InterMob/UFSCar (Interdisciplinary group of migration and mobilities research, Brazil) and the Migration Research Group at the University of Sheffield, UK), the Brazilian government, national and international organisations and migrant-led organisations and activists in Brazil. The Brazilian visit will consist of one internal workshop at UFSCar with the core team that will lead to a first conceptual reflection on HVs from a Brazilian perspective. We will visit different partners in order to map the stakeholders involved in the HVs policies in Brazil and discuss next steps and collaborations. Such stakeholders will then be invited to a national forum in Sao Paulo to collect exploratory data to understand the Brazilian humanitarian visa definition, problems and possibilities. The UK visit will involve one final workshop in Sheffield to share the final report in Portuguese and English with the evaluation of the Brazilian HVs experience, policy recommendations and lessons. We will invite other UK researchers and networks involved in HVs discussions to promote Knowledge Exchange. This project co-designed as an equal partnership between the involved actors will allow us to a) contribute to define HVs from a Brazilian perspective b) build a sustainable network of academics, decision-makers and practitioners in Brazil and the UK and c) co-construct a collaborative research environment to apply for larger grant applications. Our project will benefit the different stakeholders by recognising their voices on the topic and will contribute to potentially improve HV policies for people in need of them.

UKRI Gateway to Research · FY 2024 · 2024-12

Our health as an adult can be influenced by how we develop in the womb. Poor maternal diet during pregnancy can increase the risk her offspring will become overweight, have type 2 diabetes and heart disease as adults. While the importance of a good maternal diet is well understood, the importance of the father's diet has been overlooked. However, studies in humans and animals indicate that if the father eats a poor quality diet (too much or too little) at the time of conception, this not only affects the quality of his sperm, but can also affect the long-term cardiovascular and metabolic health of his offspring. Animal studies have played a significant role in helping us understand how parental diet may affect offspring health. Here, mice have proved especially informative as their reproduction and development are similar to humans. We have shown that feeding male mice either a low protein diet (LPD, under-nourished) or high fat diet (HFD, over-nourished) affects the expression of hundreds of genes within their testes, accelerates the rate their embryos develop and increases the size of their offspring during pregnancy. Importantly, all of these factors have been associated with increased risk of obesity, type 2 diabetes and heart disease in adult life. Indeed, we have shown that adult offspring from male mice fed LPD become over weight and developed symptoms of heart disease and type-2 diabetes. Interestingly, we observed that both the sperm and the fluid they are carried in (seminal plasma) were able to drive offspring ill-health. These observations suggest that a father can affect the health of his offspring in two separate ways; first through information carried in the sperm and second through the seminal plasma. It is these two pathways that we will explore in detail in this project. We are uniquely positioned to use our established mouse LPD and HFD models to define the mechanisms linking a father's diet with the development of his offspring. Under this proposal, we will first determine how a father's diet affects the genetic information passed on in his sperm. Specifically, we will define the sperm's RNA content, molecules known to influence gene expression within the embryo shortly after fertilisation. We will also study how these RNA molecules are packaged into the sperm as they develop and mature in the testis. Complementing these studies we will explore the cellular structure of the testes to determine how a poor quality diet affects the way they make sperm. Our second objective will study the composition of the seminal plasma and how it interacts with the sperm and the maternal reproductive tract. These interactions are important as the seminal plasma adds additional RNA molecules to the sperm after they leave the testes, preparing the sperm for fertilisation. Additionally, the seminal plasma initiates a range of immune and inflammatory responses within the uterus that prepares it ahead of embryo implantation. Therefore we will study how the seminal plasma modifies the RNA cargo of the sperm and how it affects the proteins, immune cells and blood vessels within the uterus. Following this, we will characterise the interaction between the uterus and the embryo to see if their normal communication is disrupted by poor paternal diet. Finally, we want to understand how quickly the sperm and seminal plasma can return to normal once the LPD and HFD males have been placed onto a control diet. These studies will be important for informing how permanent the effects of a poor quality diet might be for male reproductive health. This work is timely in its focus on the role of a father's diet. In addition, our focus on the role of the seminal plasma as well as the sperm means our study is also novel. We believe that understating how a father can affect the health of his offspring is critical for both informing men on how improve their chances of becoming a father and on the benefits for the health of their children.

UKRI Gateway to Research · FY 2024 · 2024-12

The aim of COGENT is to develop, analyze and apply efficient algorithms in three core areas where computer algebra plays an important role: Cohomology, Geometry and Explicit Number Theory. These will have applications to a broad range of mathematical problems, and will touch as well upon related topics like cryptography and quantum computing. Such applications of mathematics are expected to have a wide-ranging impact on economic and societal problems. Recent years have seen a plethora of high-flying projects and a dazzling variety of applications of methods in computer algebra. One of the emerging challenges is to combine ideas of different areas of computer algebra, to share expertise between them, and to educate young researchers in theoretical and practical methods with a focus of transferring knowledge and training software development skills. COGENT provides an innovative training program to facilitate this and has ambition to stimulate interdisciplinary knowledge exchange between number theorists, algebraists, geometers, computer scientists and industrial actors facing real-life challenges in symbolic computation in order to bridge key knowledge gaps. This will address the urgent need for computer assisted investigations of several longstanding conjectures in mathematics, and EU industry's need for workers with an advanced mathematical and computational skill set. Not only do we expect to merge the best known tools for these purposes with innovative approaches and ideas to extract previously inaccessible cohomological information of the underlying arithmetic groups, but we also anticipate finding new hitherto unknown concepts as we intend to enhance the currently available data pool by a whole order of magnitude. The latter will allow the researchers to find hidden patterns, with the ambition to form a solid basis for formulating novel cornerstone conjectures, ideally in the spirit of the famous Million-Dollar Birch and Swinnerton-Dyer Conjecture.

UKRI Gateway to Research · FY 2024 · 2024-12

Alternative sustainable fuels, such as hydrogen, ammonia, bio/synthetic fuels produced from sustainable pathways, have been highlighted in recent policy whitepapers as a route to address the problems in decarbonising the aviation sector and to help deliver net-zero. The recent Jet Zero Strategy has highlighted the investment to accelerate the production and infrastructure of sustainable aviation fuels (SAF), and R&D priorities in delivering Zero-emission flight. For the likes of ammonia, hydrogen and other synthetic or low carbon aviation fuels, that behave very differently to conventional kerosene-type fuels, this will entail the development of new engine technologies tailored to the new fuels, either pure component or blended. While the fundamental combustion behaviour in terms of chemical kinetic reaction mechanism may be understood for many of these fuels in isolation, at elevated pressure this is less certain, and major challenges remain concerning flame stability. FLAME project focuses on net-zero propulsion, evaluating the fuels' impact on gas turbine performance and operability. Novel optical diagnostics and models will be developed that will enable the understanding of flame quenching and the lean blow-off (LBO) limits of new bio/synthetic-derived zero/low-carbon fuels, enhancing their application in gas turbine combustors.

UKRI Gateway to Research · FY 2024 · 2024-12

We will develop spray coated solar cell technology and explore the direct deposition of high efficiency perovskite solar cells onto curved surfaces. Sush devices will add minimal weight to the surface on which they are coated and will allow energy to be generated in locations close to where it is being used, for example on the roof or body of an electric vehicle, or the cladding that is attached to the surface of a building. Our preliminary measurements suggest such a mass penalty to be around 5 grams per square metre and therefore such solar cells will add relatively little overall weight of an electric vehicle (EV), but will be capable of trickle-charging the car's battery when it is parked in the sunshine. The low weight nature of our technology is expected to be particularly important for EV applications, as reduced weight extends their maximum driving range. The carbon fibre composite materials on which we spray-cast solar cells will also be light-weight, rigid and strong and will be of importance in building applications as they could be retro-fitted as cladding to older buildings that are unable to support the weight of relatively heavy conventional solar cell devices based on silicon. This research will build a unique toolbox of manufacturing process for the production of solar cells based around ultrasonic spray-coating. The process has recently been demonstrated at small 'lab-scale'. Our aim is to scale-up this technology, making it more repeatable and increasing the efficiency by which the solar cell converts light to electricity (the so-called power conversion efficiency). The surface on which we will spray-coat devices is of critical importance; surfaces have to be very smooth and contain a low rate of imperfections. Existing research has mainly targeted glass surfaces which are very smooth, however a process to spray-coat solar-cells onto carbon fibre composites having appropriate surface requirements will be developed. This process development will enable the transfer of this technology to a variety of other composites and can be expanded to include other emerging manufacturing methods. The research will culminate in the creation of a demonstrator device that will be fabricated over a non planar carbon-fibre surface. We plan to show the demonstrator to potential end users and build a collaboration network that will further develop this technology and drive it towards commercialisation.