University of Birmingham

UKRI Gateway to Research · FY 2025 · 2025-03

The funds awarded will be used to pay for travel and subsistence costs associated with observing runs on telescopes around the world.

UKRI Gateway to Research · FY 2025 · 2025-03

This project critically examines the advancement, projection, and negotiation of "values" by Western aid donor officials in Africa. Defined here as ethical and normative principles that influence and inform political beliefs, interactions, and policies, "values" have always undergirded Western aid relationships with Africa. They have, however, recently received renewed emphasis in the policies of many Western states. Prominent among these is the UK - the focus of this study - where ministers have presented the promotion of values - "British" or otherwise - as a key plank of ensuring that post-Brexit "Global Britain" retains international influence. For "frontline" UK officials in Africa - in the case of "national" staff, African citizens themselves - this presents fundamental challenges. Donor officials are expected to uphold international aid effectiveness norms on partnership and recipient "ownership" of aid. The same officials are also, however, under domestic (UK) pressure to champion (notional) UK values abroad. In some cases, these values may be shared by African interlocutors. In others, however, UK - and other Western - officials and African stakeholders may take directly oppositional stances, departing sharply from a partnership approach. Moreover, some non-Western powers have sought to undercut Western influence through presenting their own engagement as respectful of African sovereignty. This has intersected with criticisms by African leaders of Western value promotion as "neo-colonial meddling", inconsistent, and hypocritical, which resonate with many African peoples. A recent example of how these pressures play out can be found in the international response to Uganda's draconian 2023 "Anti-Homosexuality Bill". Western officials' public condemnations were rejected by Ugandan policymakers as "arrogant" and "imperialist", while rumours of Western aid cuts were met with assurances from Beijing that Chinese aid would remain without "political strings". This project will interrogate how UK officials in Africa experience and seek to balance such challenges, constraints, and countervailing forces in their everyday work and interactions. Drawing on research in Cameroon, Kenya, Rwanda, and South Africa, the research will combine interviews, oral history, focus-group discussions, (non-/)participant observation and archival research to answer the following questions: How are "values" understood by UK officials in Africa - and by African host governments, NGOs and civil society groups, and other aid donors? How do both UK officials and their in-country interlocutors assess the effectiveness, or even desirability, of value promotion? Moreover, how does the meaning, significance, and prioritization of different values evolve for UK officials themselves, and with what implications? The research will significantly advance our knowledge of the critical role of frontline diplomatic and development staff in the negotiation of deeply sensitive and consequential areas of policy (dis)agreement and exchange. In doing so, it will refocus scholarly attention on the normative and relational dimensions of UK-Africa policy, including the wider question of what kind of "partner" post-Brexit Britain wishes to present itself as in Africa - a continent which receives over half of UK bilateral aid. Informed by an on-going engagement with practitioners from Africa, the UK, and elsewhere from inception, the research will illuminate the circumstances under which UK - and, by extension, wider Western - donor engagement can effectively amplify the work of African activists. Equally, the research will underline how and when UK and Western value promotion can not only be problematic, but actually backfire, undermining the interests of both the UK and African partners.

UKRI Gateway to Research · FY 2025 · 2025-03

The Gram-positive species Enterococcus faecium and Enterococcus faecalis can be considered prototypical bacterial generalists as they are ubiquitously present as commensals in the guts of humans and animals, while they can also cause infections in immunocompromised individuals. Worryingly, strains of E. faecium and E. faecalis have been able to acquire resistance to the last-resort antibiotic vancomycin. Vancomycin acts by binding to the terminal D-Alanine residue of the peptide stems of peptidoglycan, thus inhibiting the process of the cross-linking of peptidoglycan, which is an essential process in the formation of the bacterial cell wall. Vancomycin resistance gene clusters carried by E. faecium and E. faecalis encode enzymes which replace the terminal D-Ala residue of the peptide stems with D-lactate or D-serine. The two most common mechanisms of vancomycin resistance in both species are vanA- and vanB-type resistance. While these resistance gene clusters are functionally similar, they have evolved independently. While vancomycin-resistant enterococci have become important opportunistic pathogens, their biology has long been understudied, due to a lack of genetic tools that can be used to manipulate enterococcal genomes. In this project, we will leverage recently developed methodologies for genetic manipulation and functional genomics in Enterococcus to accurately quantify the fitness costs of vancomycin resistance in E. faecium and E. faecalis and to determine the mechanisms by which both species minimise these costs. We will generate strains of E. faecium and E. faecalis that are tagged with fluorescent markers (sGFP and mCherry) and which have the vanA and vanB gene clusters inserted in a neutral site on the chromosome. We will use three strains per species, representing different lineages of each species, to generate these constructs in. We will then perform competition assays between the different strains (with or without vancomycin resistance genes), allowing the precise quantification of the fitness costs of vancomycin resistance gene carriage in E. faecium and E. faecalis. Subsequently, we will elucidate how the transcriptional program of E. faecium and E. faecalis is impacted by the presence of vanA- and vanB-type vancomycin resistance genes through high-throughput RNA-sequencing (RNA-seq). We will also quantify the abundance of VanA and VanB on the protein level, to determine whether the data on the mRNA-level aligns with protein levels. To further explore potential differences in the regulation of vancomycin resistance between E. faecium and E. faecalis, we will determine levels of vanA and vanB expression, and the proteins they encode, after a pulse of vancomycin. If mRNA and protein levels remain high, for longer periods of time, after the vancomycin pulse, this will contribute to the energetic cost of resistance. Finally, we will use high-throughput screening of transposon mutant libraries (Tn-seq) to identify genes that contribute to minimising fitness costs of vancomycin resistance in E. faecium and E. faecalis. We will generate targeted deletion mutants in the genes identified by Tn-seq to confirm that they contribute to fitness in the presence of vancomycin and will further characterise the phenotypes of these mutants. This project will provide novel quantitative and mechanistic insights into the trade-offs between antibiotic resistance and its fitness costs in this important group of Gram-positive bacteria. Data generated in this project will open avenues for future studies in Gram-positives on the intersection of antibiotic resistance and bacterial evolution, and may inform the development of novel therapeutics to target vancomycin-resistant enterococci.

UKRI Gateway to Research · FY 2025 · 2025-03

Have you ever marvelled at the stunning symmetry of a butterfly? Or been frustrated by a photograph taken slightly off-centre? As humans we're attracted to symmetry and we encounter it every day in nature, art and architecture. It's no surprise, therefore, that symmetry plays a fundamental role across all sciences. For instance, it's the mathematical theory of symmetry that explains the tragic side-effects of the drug thalidomide seen in the 1960s. It's symmetry that provides the language for the Standard Model of theoretical physics. It's symmetry that's at the heart of novel cryptography that remains secure in an era of quantum computers. Group theory is the area of mathematics dedicated to discovering general results that apply to all types of symmetry in all contexts, from the three-dimensional shapes of molecules, to concepts from physics in 196,883 dimensions, to abstract objects admitting no simple geometric interpretation. Indeed, one fruitful way to study an object is to consider the group of all its symmetries. Just as Lego constructions can be broken into Lego bricks and as molecules can be broken into atoms, the group of symmetries of an object can be broken into smaller indivisible "simple groups". One of the greatest mathematical achievements of the twentieth century was the effort of hundreds of mathematicians across the world to classify all the finite simple groups. For decades, mathematicians have been interested in when one can obtain all an object's symmetries by repeatedly combining two well-chosen symmetries. This is called "generation", and it has yielded surprising results, with links across mathematics. For example, Liebeck and Shalev proved that "almost all" pairs of symmetries in a finite simple group generate the entire group. Moreover, just last year, Burness, Guralnick and I gave a complete classification of the finite groups where every symmetry (other than the "do nothing" symmetry) can be matched with another with which it generates the entire group of symmetries. However, these developments all concern groups of objects with a finite number of symmetries, but objects with infinitely many symmetries are very important in contemporary mathematics. My proposal is to begin a new programme of research to generalise developments on generation to the infinite. More precisely, I seek to investigate whether the startling generation properties of the finite simple groups hold for the infinite simple groups such as Thompson groups and related groups of homeomorphisms of Cantor space, with a view to forming a deeper understanding of the generation properties of finitely presented infinite simple groups. In addition, by exploiting recent developments in the theory of finite (almost) simple groups, I will address open questions regarding the generation of finite groups. I propose carrying out this research at the University St Andrews, which is home to a number of leading researchers in both finite and infinite groups. Moreover, it hosts CIRCA, a research centre joint between mathematics and computer science. This highlights potential applications of the proposed programme of work: from cryptographers to chemists, researchers carry out computer calculations involving symmetry, and knowing that all the symmetries of an object can be generated by just two provides an efficient way to carry out many of these computations.

UKRI Gateway to Research · FY 2025 · 2025-03

‘Developmentally-regulated GTP-binding proteins’ (DRG1 and 2) are highly conserved GTPase enzymes that bind to ribosomes to promote protein synthesis (translation). We recently discovered that DRG proteins are modified by hydroxylation, an emerging protein modification with largely unappreciated and poorly understood roles in fundamental cellular processes. Protein hydroxylation in humans is generally catalysed by oxygenases that are dependent on a metabolite called 2-oxogulatarate (2OG, otherwise known as alpha-ketoglutarate). These so-called ‘2OG-oxygenases’ have nutrient-sensing capabilities that can render their functions sensitive to oxygen limitation (hypoxia) and metabolic alterations. DRGs are hydroxylated by a 2OG-oxygenase called Jumonji-C-domain 7 (Jmjd7) to regulate RNA binding. However, the exact molecular functions of hydroxylation and the wider biological roles of DRGs remain elusive. Although DRGs are reported to be cytoplasmically-localised, consistent with their translation factor role, we also observe DRG1 in the nucleus, where we discovered it interacts with an E3 ubiquitin ligase of unknown function. We recently identified a candidate substrate of this orphan E3 ubiquitin ligase that is involved in nucleosome remodelling. Based on a solid foundation of pre-existing data including protein interaction assignments, functional studies, and novel models, we will now focus on understanding the importance of hydroxylation and DRG1 function in nuclear ubiquitin biology. We aim to first provide a comprehensive molecular understanding of the different protein:protein interactions in this novel signaling pathway and the signals that regulate nuclear versus cytoplasmic DRG1 localisation and target engagement. The insights gained from this work will then provide a comprehensive framework for subsequent biochemical and functional studies. We will investigate the regulation of E3 ubiquitin ligase activity by DRG1 and Jmjd7 and characterise how ubiquitylation regulates the function of the nucleosome remodelling factor. Finally, we will investigate the physiological importance of this exciting new pathway by examining its role in transcription and DNA damage repair. Together, the work will significantly advance our understanding of hydroxylase biology, elucidate how a cytoplasmic GTPase regulates a nuclear E3 ubiquitin ligase, and shed important new light on the relationship between translation and transcription-associated processes in eukaryotes. Overall, the findings will deliver important new insights into the rules of life that can be used to better understand the human diseases associated with this exciting new pathway in the future.

UKRI Gateway to Research · FY 2025 · 2025-03

Algorithms are ubiquitous in all aspects of our daily lives. Given their importance both on a personal and societal level, it is essential that we are able to design algorithms for fundamental computational problems which are both (i) correct and (ii) fast (i.e., running in polynomial time in the input size). However, under the well-believed hypothesis of P!=NP from theoretical computer science, it is impossible to design algorithms which achieve both these properties for most interesting real-world tasks, e.g. choosing the optimal order in which to visit a given set of destinations such that the total distance travelled is minimized. If one insists on algorithms which are guaranteed to be provably correct, then the cost must be paid in the running time which is a big (exponential) function of the input size. This can severely limit the use of algorithms in applications: for example a running time of 2N quickly becomes infeasible in practice, even for relatively small input sizes such as N=300 this exceeds the estimated number of atoms in the universe! This intractability led to the development of two areas of algorithmic research:  1. Approximation algorithms: We relax the requirement of being correct, but the algorithm is required to be fast, i.e., run in polynomial time in size of the input. 2. Fine-grained algorithms: We require the algorithm to be correct, but relax the requirement of the algorithm being fast: an additional factor is allowed in the running time which can be any function of carefully chosen parameters which capture tractability of the given problem Both of these areas are at the forefront of research in theoretical computer science with hundreds of results each year. However, there is now evidence that a large class of computational problems (e.g. Clique, Directed Multicut, etc.) are not tractable with respect to either approximation algorithms or fine-grained algorithms. For such problems, the paradigm of fine-grained approximation algorithms is a next natural step where we relax both conditions: the goal is to find approximate solutions while allowing running time which is beyond polynomial time. Although this is a nascent area of research in computer science with only a few results (mostly in the last 5-7 years), it is known that there are problems which are not amenable individually to either approximation algorithm or fine-grained algorithms but the one-two punch of fine-grained approximation algorithms leads to improved theoretical guarantees. This project has two main research objectives: 1. Develop the theoretical foundations of this hitherto unexplored paradigm of fine-grained approximation algorithms 2. Introduce this paradigm to researchers in fields beyond theoretical computer science Our project will push the boundaries of tractability in algorithms research. Additionally, we will provide practitioners with a new suite of algorithms (with improved performance guarantees) for fundamental computational problems that need to be solved in real-world applications.

UKRI Gateway to Research · FY 2025 · 2025-03

Microsystems are a diverse range of miniaturised devices designed to interact with their surroundings, collect data or perform other tasks. The global microsystems market is estimated to be worth $31.6 billion, which does not include the added value that innovation in microsystems research has contributed to other markets that benefit from its success, such as robotics, healthcare monitoring, automotive safety and much more. However, microsystems research across the UK is in danger of decline. There are several reasons for this. Firstly, the community is fragmented, with no central hub in the UK to bring academic and industrial players together. This limits the ability of industry to engage with academia, impeding knowledge transfer and impact, restricting academics from understanding industrial needs and hindering the ability of industry to identify researchers with the needed skills to solve a specific problem. This is exacerbated as microsystems research across the UK is disparate, with many microsystems researchers more likely to align themselves with specific application areas rather than the broader microsystems community. We intend to establish a network to sustain and grow microsystems research across UK industry and academia, whether fundamental or applied and create a focal point around which the community can coalesce and grow. This network will identify the diversity of microsystems research activity across the UK, mapping current UK strengths and weaknesses and highlighting future strategic priorities for microsystems research, which the UK is competitively placed to lead. Secondly, there are perceptions within the community that the complexity of fundamental microsystems research is not appreciated in its own right, with only applied microsystems research being of interest to funding bodies. Greater advocacy is needed for microsystems and how advances in fundamental research will benefit this and other fields. The lack of a unifying voice led by a central hub impedes advocacy and inspiring the next generation of microsystems researchers, both of which are necessary to grow this discipline. The network will also highlight the benefits of microsystems and disseminate microsystems research to the wider academic community, general public and other stakeholders through several activities, such as the website, seminars and workshops. Thirdly, the lack of a central hub has hindered the sharing of expertise and access to facilities. Much microsystems research relies on siloed experts and expensive cleanroom equipment. Failure of this equipment or environment can significantly disrupt research. A central hub through which access to equipment can be facilitated would help mitigate this while ensuring greater financial sustainability for cleanrooms by reducing under-utilisation and providing more effective usage of existing funder investment. Finally, the lack of a central hub has impacted the ability of the community to secure large microsystems research projects, which will support the health of the field and provide outcomes that will benefit other application areas. The network and the underpinning nature of microsystems will lead to new multidisciplinary research proposals contributing to the strength of a diverse range of portfolio areas. Furthermore, greater community cohesion due to the network will facilitate applications for large strategic bids vital to the health of the discipline, such as CDTs. This network will support the delivery of several priorities and cross-cutting themes described by the EPSRC Tomorrows Engineering Challenges report, such as "underpinning tools and techniques" and "strengthen mechanisms to facilitate and fund multidisciplinary research".

UKRI Gateway to Research · FY 2025 · 2025-03

The Intelli-Ingest Doctoral Network will train 13 researchers in the development of minimally invasive, orally delivered miniaturised devices. This ingestible technology has the potential to unlock significant advances across the medical sciences, whether it is enhanced diagnosis through the application of artificial intelligence or the integration of multiple sensors into these devices, surgery through less invasive biopsy or treatment through targeted drug delivery direct to the site of interest or the development of therapeutic form factors that can safely reside within the gastrointestinal tract for extended periods, removing the need for daily treatment and improving the adherence of patients to the treatment regimen. However, to achieve this potential, several scientific challenges must be addressed. These include needing more accurate localisation, improving our ability to know where the devices are along the gastrointestinal tract at any time for better treatment and repeated diagnosis. The second challenge is the need to integrate more advanced diagnostic and therapeutic technology, which is vital for more accurate identification and treatment of pathology. The third challenge is environmental sustainability; more sustainable designs are crucial due to the single-use nature of most ingestible devices and their growing use post-pandemic. Finally, to rapidly innovate in the ingestible device field, we need better tools to advance translation at low cost, reducing the use of costly animal models. The 13 doctoral candidates will tackle these challenges, advancing the state of the art in ingestible device technology while benefiting from multidisciplinary, multi-sectoral, international training provided by leaders in this field. This training will provide these candidates with extensive technical, translational and transferable skills training that will enhance their future career prospects in this growing field of research.

UKRI Gateway to Research · FY 2025 · 2025-03

According to World Health Organisation (WHO) findings, noise is the second largest environmental cause of health problems in Europe, just after the impact of air pollution. With regards to this, noise generated by unsteady turbulent flows is one of the key contributors, including noise emitted from transport vehicles and wind turbines. Despite the recognised impact of aerodynamic noise, there is a lack of clear understanding regarding the specific dynamical processes through which turbulence radiates noise. This lack of understanding has hindered efforts to efficiently reduce noise generated by turbulence. With the advancements in computational power and numerical methods, high-fidelity flow simulations become more affordable to generate high-quality flow datasets and offer unprecedented opportunities to examine the noise generation process in great detail. In light of this, the aim of this project is to leverage high-fidelity simulations with modern data-driven approaches to unravel the nonlinear dynamics of noise generation by turbulent flows. To this end, this project will (a) characterise the nonlinear dynamics involved in noise generation from a dynamical system perspective in the frame of high-fidelity simulations and (b) understand the nonlinear mechanisms that underpin the noise-generating dynamics with a low-dimensional dynamical model derived from simulation data. The project will advance our fundamental understanding of the dynamics of noise sources generated by turbulence, leading to a new paradigm of noise reduction strategies for controlling turbulence dynamics on top of the kinematics.  In collaboration with Rolls-Royce, the project will have a direct impact on aircraft engine noise reduction by offering a powerful toolset to develop a physical understanding of jet noise sources on the current designs and provide guidance on low-noise design optimisation. This will contribute to the growth of air transport without detrimental impact on community noise and help to maintain the UK aerospace’s leadership in developing new technology with a potential contribution of around £114 billion to the UK economy over the next 20 years. Since turbulence-generated noise is central in most aeroacoustics applications, the project is expected to produce a broad impact on noise reduction for land vehicles and wind turbines, which will benefit the whole society by creating a better living environment.

UKRI Gateway to Research · FY 2025 · 2025-03

Numerous tissues within our bodies continuously adapt to environmental cues over time. In a healthy state this enables growth, movement and regeneration but these time dependent changes are also apparent in many diseases and as we age. However, when we engineer medical devices to replace or repair these tissues time responsive properties are not typically considered or incorporated. In fact, the current healthcare technologies ecosystem discourages these dynamic behaviours despite them being so integral to healthy tissue function. This lack of adaptability may compromise the functionality or limit the lifespan of healthcare technologies that are critical components of patient’s quality of life and wellbeing. For example, stoma bags that leak as the abdomen changes during movement or facemasks that do not maintain an airtight seal while a clinician talks to their patient. The aim of this network plus award is to inclusively transform engineering mindset into 4-dimensions enabling the innovation of a new dynamic medical device era. This will be achieved through a series of objectives: O1 Identify and connect expertise across the healthcare technologies ecosystem O2 Embed diversity into the network’s culture and activities O3 Educate and share best practice in enabling 4D functionality O4 Support progression of new ways of achieving 4D healthcare technologies O5 Promote and assist strategic funding bids from network members   Through co-design of our network with various stakeholders we have identified key challenges to tackle in developing a community capable of bringing to life 4D medical devices. The first phase is to build our community through development of technical forums that shall support upskilling, knowledge exchange and promote dialogue. By centralising stakeholder co-delivery in our network’s model we will bring inclusivity to the forefront of medical device design and deployment. This will ensure that the 4D Health Tech era is one in which medical devices are designed for all through diverse data inputs, tested to account for natural physiological variations and trialled on varied sub-population groups.   Seed-corn funding and the network’s innovation fellow will support the community bringing to life new 4D Health Tech capacity. Funds to enable our community members to mobilise and engage in new ways have also been requested. The network’s central team will build interactive resources to ensure that 4D Health Tech is an outward facing innovation hub committed to inspiring the next generation through its creativity as well as informing its stakeholders, including the public, about its progress.   4D Health Tech will ignite new technical frameworks for medical devices enabling them to function in novel ways that extend lifespan and offer patients improved outcomes. In creating this influential community we have carefully designed flexible and agile support mechanisms to ensure that it will be a beacon of diversity both conceptionally and in terms of its membership. As such this network plus award represents a springboard for meaningful change at a time in which fit for purpose medical devices will greatly impact national wellbeing and prosperity.  

UKRI Gateway to Research · FY 2025 · 2025-03

Context: Metal-organic frameworks (MOFs) and their nanoscale counterparts (nMOFs) have shown remarkable application versatility, spanning catalysis, energy storage, and environmental remediation. Their intricate structures, formed by combining metal ions and organic ligands, hold tremendous promise. Yet, despite their broad utility, a significant knowledge gap exists in understanding how the structural and biogeochemical transformations of nMOFs impact environmental/human health and efficiency in environmental applications. These concerns align with global sustainability objectives aimed at addressing emerging environmental risks posed by novel chemicals. To harness the full potential of nMOFs while mitigating adverse effects, it is imperative to comprehensively investigate their structural and biogeochemical transformations in diverse environmental conditions and understand their implications for both ecosystems and human health. This research project seeks to bridge these critical knowledge gaps, promoting the responsible and sustainable utilisation of nMOFs and advancing global sustainability goals.   The Challenge: The challenge this project addresses is multifaceted. While nMOFs offer tremendous opportunities for applications that benefit society, there is a growing need to understand their behaviour in real-world environmental settings. The challenges include: Environmental Fate: It is unclear how nMOFs undergo structural and biogeochemical transformation and react when exposed to various environmental conditions, such as air, liquid, and organisms. This knowledge gap hinders our ability to predict their behaviour in ecosystems. Toxicological Impacts: The potential toxicological impacts of nMOFs on ecosystems and human health are poorly understood. As their use expands, there is a growing concern about their unintended effects. Sustainability and Responsibility: Ensuring that nMOFs are used safely and responsibly is vital. By addressing these challenges, the project aligns with global sustainability goals and initiatives to mitigate the risks posed by emerging chemical substances in the environment.   Aims and Objectives: The project's primary objective is to investigate nMOF structural and biogeochemical transformations, addressing their impact on ecotoxicity and application efficiency. This encompasses objectives (O) like synthesising viable nMOFs and conducting characterisations (O1), optimising transformation studies across primary, secondary, and tertiary stages (O2), employing advanced analytical techniques for structural and biogeochemical investigations (O3), assessing and correlate transformation with ecotoxicological impacts (pristine vs post-transformation) (O4), evaluating application efficacy, stability, reusability, and recyclability of nMOFs (pristine vs post-transformation) (O5), and disseminating research outcomes through Science Communication at the community level (O6). Potential Applications and Benefits: Environmental Impact Assessment: Understanding nMOF behaviour in environmental settings will enable more accurate predictions of their impact on ecosystems. This knowledge is crucial for informed decision-making in environmental management. Health Implications: Investigating potential toxicological impacts on human health contributes to safer material development and helps safeguard human well-being. Sustainable Material Design: The project supports the development of Safe-and-Sustainable-by-Design (SSbD) principles for nMOFs, promoting their responsible use and minimising their adverse environmental and health effects, increasing their application efficacy. Global Sustainability Goals: By addressing knowledge gaps related to emerging materials, this project aligns with global sustainability initiatives, advancing goals related to clean water access and ecosystem preservation. In summary, this research project represents a significant step toward unravelling the potential of nMOFs while ensuring their responsible and sustainable use. It offers a deeper understanding of their behaviour in diverse environmental conditions, which is vital for both ecological and human health. Moreover, it promotes adopting SSbD principles to mitigate adverse impacts and contribute to a healthier and more sustainable world.

UKRI Gateway to Research · FY 2025 · 2025-03

Neck pain (NP) remains one of the leading causes of disability worldwide, resulting in financial burden and poor quality of life. The incidence has steadily increased since 1990, with data from the UK showing the largest increase. In 2020, more than 203 million people suffered from NP globally, and this number is expected to grow by more than 30% over the next three decades. Of those who experience an episode of NP, between 50 and 85% will report NP 1-5 years later, with over 20% of people developing recurrent pain episodes. In June 2022, more than 250,000 individuals in the UK had back or neck pain severe enough to cause them to leave work. Despite being a research priority, the factors contributing to the development of new episodes of NP remain poorly understood. Understanding these factors, would allow targeted interventions and preventative measures. Advancing research on NP recurrence implies overcoming significant challenges, including (i) acknowledging the multidimensional nature of NP, encompassing physical, psychosocial, and environmental factors, and (ii) employing methodologies capable of managing such complexity while monitoring NP progression over time. Previous research has often focused on a single domain, largely overlooking the variation in individual and contextual physiological responses to pain. Moreover, previous studies have predominantly concentrated on patient-reported outcomes, exploring what patients perceive and how they relate to their health condition with limited attention to physical impairments associated with NP. Yet, our research has shown that individuals with recurrent NP exhibit persistent physical alterations when in remission from their pain, and these physical factors may potentially play a role in NP recurrence. A comprehensive, multidimensional approach is therefore essential to address the complexity of NP and identify predictors of new NP episodes. This approach must recognise the fluctuating and recurrent nature of NP, characterised by periods of symptom exacerbation and remission. Based on established research priorities and recognised challenges in NP research, the primary aim of this project is to identify physical and psychosocial predictors related to the development of new NP episodes in people with recurrent NP. Predictors of future NP episodes and pain severity will be identified to develop clinical prediction models for estimating individualised risk of NP recurrence over a 12-month period. Additionally, we will monitor behavioural and environmental factors during the 12-month period to investigate whether changes in these fluctuating factors are related to new episodes of NP. To achieve these goals, we will use different data-driven approaches within a biopsychosocial framework. The findings from this project will reveal factors that can help predict the development of future NP episodes, and thus aid in the development of a clinical prediction tool, helping clinicians in identifying patients at higher risk of experiencing new and more severe NP episodes. By identifying at-risk individuals and relevant modifiable predictors, the prediction model will enable the implementation of early intervention strategies, tailored rehabilitation programs, and personalised preventive measures. These efforts aim to reduce both the frequency and severity of NP episodes to improve quality of life for those affected. The predictors identified for future NP episodes could represent potential treatment targets, important for consideration in future randomised controlled trials. This will guide clinicians in making informed decisions about the most appropriate and effective treatment plans for their patients, which ultimately may reduce healthcare costs associated with recurrent NP.

UKRI Gateway to Research · FY 2025 · 2025-02

To meet its legally-binding target of achieving net zero emissions of greenhouse gases (GHG) by 2050, the UK must eliminate GHG emissions from homes. This enormous task involves retrofitting—the process of upgrading the energy efficiency—of the 29 million homes. These retrofits will significantly change indoor environments, bringing health co-benefits by improving home warmth during the winter and providing protection against harmful outdoor air pollutants. However, if not done properly, these modifications can trap indoor air pollutants and moisture, deteriorating indoor air quality and causing issues such as damp/mould. These conditions can adversely affect health and wellbeing, particularly for the most vulnerable in society, such as older people and those with pre-existing conditions like asthma. An opportunity and challenges Retrofitting the UK's homes will require a substantial investment—estimated at £250 billion by 2050. This offers an unprecedented opportunity to enhance environmental and socio-economic outcomes, including public health improvements and reduced inequalities. However, our current lack of scientific knowledge and tools hampers our ability to fully capitalise on this potential. Specifically, we lack understanding of how retrofitting impacts the indoor environment and health in real-world scenarios and we do not have comprehensive tools to assess both positive and negative health impacts of retrofit options. Furthermore, our insights into the complex interactions among the indoor environment, health, inequalities, behaviours, and regulatory and financial frameworks are limited. The INHABIT Hub has been specifically established to tackle these complex challenges.

UKRI Gateway to Research · FY 2025 · 2025-02

Obesity is a growing global health concern, affecting more than 650 million people worldwide and predicted to cost over US$1 trillion by 2025. The adipose tissue serves as an important storage of energy in the form of fatty acids contained in fat. Inside adipose cells, fatty acids are stored in specialized cellular structures known as 'lipid droplets', from where they are released during fasting in a process termed lipolysis. When someone develops obesity, their body stores an excessive amount of fat, leading to health problems. One major issue is that fat accumulation significantly increases the risk of cardiovascular diseases such as heart attacks and strokes. Additionally, it can lead to insulin resistance, causing diabetes, and inflammation, affecting the function of several organs such as the liver. This project addresses the urgent need to better understand the fundamental cellular and molecular mechanisms that control the storage and release of fatty acids in order to develop improved therapies for obesity-related metabolic disorders. G-protein-coupled receptors (GPCRs), the largest family of receptors in the human body and ideal drug targets, are well known to play important roles in the control of fatty acid storage and release. However, progress in the field has been hampered by the long-held belief that these receptors were only active at the cell surface, and, therefore, could not sense the intracellular concentration of metabolites such as fatty acids. While this dogma has been challenged by us and other with the demonstration that GPCRs can also function inside cells, the relevance of these emerging ideas for metabolite-sensing GPCRs remains to be explored. Free fatty acid receptors 2 and 4 (FFA2/4), two GPCRs activated by fatty acids in adipose cells, are under consideration as potential drug targets for obesity-related metabolic disorders. Exciting preliminary results by our team indicate that FFA2/4 might have to be precisely located and function inside cells in close proximity to lipid droplets to efficiently sense the released fatty acids and inhibit lipolysis. However, the underlying mechanisms, physiological relevance and implications for drug therapy of this novel potential modality of 'intracrine' FFA2/4 signalling are presently unknown. In this application, we will combine state-of-the-art cell signalling, pharmacology and advanced imaging techniques with innovative cell and mouse models as well as tissue samples from patients with obesity to elucidate the cellular and molecular mechanisms of 'intracrine' FFA2/4 signalling, its relevance to human physiology and disease, and implications for drug therapy. Our research holds promise for identifying novel molecular mechanisms involved in the control of fatty acid storage and release in physiology and disease, with potential implications for the therapy of obesity-related metabolic disorders.

UKRI Gateway to Research · FY 2025 · 2025-02

In 2019 the MRC and NSFC funded our DETECTIVE network to study the transmission of Multi-Drug Resistant Gram negative (MDR-GN) bacteria in Chinese Intensive Care Units. Four years later we have shown unimaginable levels of introduction of these pathogens into the clinic from the community, and onward transmission in the ICU. What we do not know is why this is so significantly different from the UK where presence of these pathogens as clinical threats in the ICU is much rarer. To address this knowledge gap we present DETECTIVE-II. In this proposed project we will study 3 inter-connected objectives: 1) We will monitor the extent to which MDR-GN disseminate from the hospital back out into the community in China and the UK by performing genomic surveillance in ICU patients, patients attending hospital from the community as out-patients, and wastewater samples allowing us to determine the onward fate of clinical MDR-GN outside of the Hospital setting. 2) We will determine if there are different adaptations to the clinical and non-clinical environments in UK and Chinese strains that may explain their differential abundance in the two locations. In particular we believe Chinese strains may be very successful because they are specially adapted to colonising the human gut, much more so than that strains we see rarely in UK Hospitals. We can test this using lab based models of the human gut and competing Chinese and UK strains. 3) We will determine if there are inherent differences in the ability of UK and Chinese strains to acquire and successfully integrate mobile genetic elements. This is a crucial process in bacteria becoming MDR and also acquiring new genes that may make them better at colonising the gut. We can compare the extent to which UK and Chinese strains take DNA from each other and determine if the successful Chinese strains are more prone to taking up and DNA and changing their physical properties as a result. Together these objectives should provide a definitive analysis of the reasons why MDR-GN pathogens are established as clinical threats in the ICU setting in China but not the UK. We believe our data could identify true clinical-relevant information that could help reduce MDR-GN prevalence in Chinese clinical settings as well as ensure prevalence remains low in UK clinical settings.

UKRI Gateway to Research · FY 2025 · 2025-02

Cosmology is at the threshold of a new era. The standard, Lambda-CDM, model, till recently, has been an excellent explanation of observations in the early and late universe. The recent tension between the local Hubble constant (H0) and the inference from early universe, is a strong challenge to Lambda-CDM, with profound consequences for particle physics and cosmology. While this tension can be a sign of novel physics, e.g., a contribution from massive neutrinos or a modified theory of gravity, it can also be a realization of unknown systematic effects. It is, therefore, urgent to explore such measurements from more than one method. This project will tackle the open question "is there new physics beyond Lambda-CDM?" with cutting edge transient surveys in three steps: 1) Developing strongly lensed supernovae as an exciting new probe of H0, independent of either the early universe or the local distance scale. 2) sidestepping known systematics in local H0, by constructing a unique distance ladder from Type Ia supernovae (SNe Ia) observed by a single survey, the Zwicky Transient Facility (ZTF) 3) pioneering an empirical test of the directional dependence of H0 using the SN Ia magnitude-redshift relation. The Vera Rubin Observatory (VRO), online imminently, is expected to discover hundreds of lensed SNe. Utilizing state-of-the-art spectrographs, e.g., NOT and 4MOST, we will build a sample of lensed SNe from the VRO and measure H0 with 1.3% accuracy. Implementing modern methods for distances to the ZTF SN Ia host galaxies from tip of the red giant branch (TRGB) stars, we will overcome the current largest distance scale error sources, i.e. host galaxy bias and calibration. Forthcoming spectroscopy surveys will allow precise inference of ZTF SN Ia host galaxy redshifts, shedding light on potential anisotropies in the Hubble constant. These interconnected channels for measuring the Hubble constant and its directional dependence will enable a precise and accurate test of Lambda-CDM.

UKRI Gateway to Research · FY 2025 · 2025-02

BACKGROUND AND IMPORTANCE: To survive and proliferate, cancer cells must maintain the DNA at the ends of their chromosomes, called telomeres, which are comprised of long arrays of repetitive DNA sequences. In normal cells, these sequences shorten each time the cell divides, limiting the cell’s lifespan. Cancer cells maintain these sequences to grow indefinitely. Therefore, targeting the mechanisms of telomere maintenance represents a likely strategy to selectively kill cancer cells. Most cancers maintain their telomeres via a protein called telomerase. However, 10-15% of cancers engage the Alternative Lengthening of Telomeres (ALT) mechanism. There are currently no useful treatments for ALT-reliant cancers, which include brain tumours such as aggressive high-grade glioma. Moreover, the identification of biomarkers for the diagnosis and stratification of ALT-reliant cancers are sorely needed. Therefore, understanding the ALT mechanism will lead to therapies to treat ALT-reliant cancers, including high-grade glioma. ALT-reliant cancers utilise a DNA repair mechanism at clustered telomeres to mediate telomere elongation called break-induced telomere synthesis (BITS).  While some progress has been made regarding the ALT molecular mechanism, several key questions remain: 1. How is BITS coordinated with other DNA repair processes? 2. How is BITS engaged at clustered telomeres? 3. How does DNA replication and repair during BITS influence telomere length and sequence composition? Answering these questions will elucidate the molecular mechanisms of ALT and the processes of replication fork stability and DNA-repair pathway choice in human cells. Moreover, drugging components of the ALT machinery and/or exploiting synthetic sick phenotypes between factors promoting ALT and other DNA repair processes represents a likely strategy to kill ALT-reliant cancers. Therefore, this work may improve patient outcomes for ALT-reliant cancer sufferers, including high-grade glioma patients. I will answer the above key questions via three interconnected yet independent research objectives: OBJECTIVES: Define the interplay of BITS with other DNA repair mechanisms. Reveal the mechanisms of ALT telomere clustering. Determine how ALT telomere replication and repair impact telomere sequence. OUTCOME: Objective 1 will determine the contribution of Microhomology-Mediated End-Joining (MMEJ) to ALT telomere maintenance (my data suggests MMEJ engages ALT+ telomeres) and will establish the genetic relationships between BITS and MMEJ in the context of ALT. This work will extend our understanding of the factors required to promote ALT cancer cell survival and will identify therapeutic targets for the design of small molecule inhibitors to treat ALT-reliant cancers. Objective 2 will uncover the molecular mechanisms of telomere clustering crucial to ALT engagement and will determine moieties of the BLM and SMC5/6 proteins required to promote clustering which may be targeted for inhibition to selectively eliminate ALT-reliant cancers. Moreover, this objective will determine if clinically relevant drugs impact telomere clustering and therefore may represent effective treatments for ALT+ cancers. Objective 3 will determine the impact of replication fork progression, collapse, and subsequent repair on telomere sequence in both ALT-reliant and telomerase-positive cells. This will uncover the molecular origins of “telomere variant sequences” associated with ALT engagement and may uncover biomarkers to diagnose and/or stratify ALT-reliant cancers. Collectively, this work will shed light on the fundamental biological processes of DNA replication, DNA double-strand break repair and telomere maintenance and may uncover therapeutic targets and biomarkers for the treatment of ALT-reliant cancers including high-grade glioma, benefiting cancer patients, the NHS and other equivalent health services worldwide.

UKRI Gateway to Research · FY 2025 · 2025-02

Each of the cells in our body has approximately 2 meters of DNA that needs to be accurately copied every time a cell divides. Mistakes that occur during DNA copying are a major contributing factor towards the development of genetic diseases, cancer and early aging. DNA damage is one of the main causes that prevents cellular DNA being copied properly and can occur either through normal processes during cell growth or can be caused by exposure to radio/chemotherapy or environmental toxins. Excessive DNA damage is extremely toxic, and this forms the basis for why radio- or chemotherapy is used to kill tumour cells. However, cells have evolved complex mechanisms to recognise and repair DNA damage so that the DNA can be copied without any errors. When DNA is being copied, this is carried out by many proteins that work together as part of a big machine, called the replisome, to unzip, copy and rezip the entire DNA molecule. When the replisome finds damaged DNA, the copying process stops. If the DNA damage is not repaired properly and copying restarts, this can cause chromosomes to break and cells to die. However, when the replisome meets DNA damage, cells have developed an elegant process that pauses the copying process and allows the replisome to back track so that the DNA repair machinery can repair the damage. This is called replication fork (because as the DNA is unzipped and copied it looks like a 'fork') reversal. Replication fork reversal is a vital process for the repair and restart of DNA duplication, but represents a period of vulnerability. If the replisome and reversed replication fork are not stabilised and protected, the replisome can fall off and the newly copied DNA can be into pieces by proteins called nucleases. This can lead to the breaking or loss of chromosomes and increased mutations, all of which are known to contribute to human diseases. Whilst we understand a lot about how damaged DNA causes replication fork reversal and some of the proteins involved, there are still many unknowns. However, it is clear other proteins engaged in this process still remain to be identified. As such, it is imperative that when new proteins are found, their roles in controlling replication fork reversal are identified. This will give us vital knowledge about how healthy cells respond to DNA damage and what happens when this process goes wrong. This project will focus on understanding the function of a new protein called N4BP2 and how it controls replication fork reversal. N4BP2 is a unique protein in that it can modify DNA in two completely different ways: One is a chemical modification of the ends of DNA, called phosphorylation, and the other is to cut DNA when it forms unnatural shapes. This indicates that N4BP2 aids repair of damaged DNA undergoing duplication in two independent ways. Since there is no other protein in the cell similar to N4BP2, understanding how N4BP2 controls replication fork reversal could uncover a completely new mechanism with which damaged DNA is repaired before it is copied. We will use a combination of genetic and biochemical approaches to study N4BP2 function. First, we will identify what type of DNA damage N4BP2 recognises and what happens to the process of copying DNA when N4BP2 is lost. Second, we will identify what types of unusual DNA structures N4BP2 prefers to modify. Third, we will determine how N4BP2 controls individual proteins that make up the replisome at damaged forks. Combined, this approach will give us a good understanding of how N4BP2 regulates replication fork reversal to preserve DNA duplication and protect chromosomes from breaking. Lastly, these studies will complement a separate, but related study that is focused on determining the impact that loss of N4BP2 has on the development of embryos using a mouse model.

UKRI Gateway to Research · FY 2025 · 2025-02

This fellowship will pioneer a unique approach to magnetic resonance imaging (MRI) contrast agent design, providing a solution to the safety and environmental concerns associated with current agents. MRI is an essential tool for medical diagnosis. Contrast agents play a crucial role in improving the images obtained, and hence patient outcomes. Most clinical MRI contrast agents are based on gadolinium, due to its electronic structure. However, there is growing evidence of gadolinium deposition in the bones, skin, brain, and internal organs of patients following exposure to these contrast agents. This is particularly concerning for patients that require repeated administration of contrast agents and for children. For patients with kidney problems, there is also a clear link with a potentially fatal condition called nephrogenic systemic fibrosis. Furthermore, the use of gadolinium-based contrast agents is now a recognised source of environmental contamination of water sources. There is a clear need to develop gadolinium-free MRI contrast agents. New MRI contrast agents would need to be as efficient or better (requiring lower doses) than current agents, be as stable and display no toxicity. The potential for "smart" targeted agents provides an exciting opportunity to improve medical diagnosis. This fellowship will develop a completely new solution to MRI contrast agent design, and trial these in preclinical studies. We design brand new proteins from the simple building blocks of human life: amino acids. Many proteins in the human body use a metal and our new proteins can be designed to give a metal ion specific properties. In this case, we can tune the properties of a copper ion to behave as a contrast agent. And one that is more "efficient", better, than current agents. This was previously thought to be impossible! Using a biologically essential metal ion (essential for correct biological function), such as copper, is exciting as our bodies already know how to process and remove trace amounts of these metals if needed. Unlike gadolinium which will accumulate in the body over time. This fellowship will explore the full range of essential metal ions (e.g., copper, manganese, iron, nickel, cobalt etc.) bound to these new proteins and screen their performance as MRI contrast agents. The most promising combinations will be optimised, taking advantage of computers to rapidly screen and improve thousands of designs. Lead designs will then be prepared and their performance validated experimentally, in terms of their "efficiency" as MRI contrast agents, their stability and ultimately their toxicity. One work package takes advantage of the protein, to develop a "plug and play" strategy to access "smart" targeted MRI contrast agents. The overall lead, top-performing MRI contrast agent candidate, will be progressed to preclinical studies.

UKRI Gateway to Research · FY 2025 · 2025-02

The UK has a unique opportunity to lead the way in the rapidly growing fields of artificial intelligence (Al) and digital healthcare. To consolidate its position as a global leader in this field, the UK needs to ensure regulation is optimised to accelerate innovation ('pro-innovation') whilst also ensuring these technologies are safe, cost-effective, equitable, and sustainable ('responsible innovation'). Regulatory science utilises scientific methodology to support this optimisation process, but most regulators currently lack this expertise 'in-house', especially for novel and advanced technologies. Ensuring regulators strike this balance will be the remit of the UK Centre of Excellence for Regulatory Science and Innovation (CERSI) for Al and Digital HealthTech. Our CERSI will bring together experts working in different sectors to enhance the efficiency, effectiveness, safety, fairness, and sustainability of regulation and innovation. It will do so by connecting experts and supporting their ability to work together on pressing scientific questions which have the capability to streamline regulatory assessments and policy, facilitating a faster translation of these technologies from concept to consumer whilst upholding and enhancing principles around safety and equity. "

UKRI Gateway to Research · FY 2025 · 2025-02

Fusion Forest is a radically novel and interdisciplinary approach to design our future treescapes. We face a challenging scenario, where tree cover needs to be increased - the UK government has set out a 25-year programme to plant 180,000 hectares of trees by 2042 and to increase the woodland cover to 12% by 2060 - whilst there is an alarming increase in tree epidemics. These outbreaks, favoured by increased disease portability, chemical resistances and climate change, compromise the future of our woodlands, producing a dramatic loss of biodiversity and resources. We propose a proactive strategy where new plantations are designed from the onset to halt and suppress diseases using their natural immunity. Fusion Forest achieves so by cutting through discipline boundaries and establishing synergies among the latest discoveries and techniques in tree immunity, ecological modelling and fluids modelling. Fusion Forest seeks to understand how to stimulate priming of defence in trees by using careful combinations of species and lowering the disease pressure. In parallel, the project incorporates the often overlooked spatial component of forest canopies and uses forest heterogeneity to our advantage, creating physical barriers that complement and enhance the ecological ones. To do so, we design a new interdisciplinary modelling framework - named ForestFlow - that brings together forest growth models and computational fluid dynamics. The understanding gained from the ecophysical model, complemented by field and laboratory measurements, allows for a change of paradigm in the way we confront tree epidemics. The response to tree disease outbreaks is mostly reactive, focused on monitoring, chemical treatments and tree felling, with the subsequent environmental and economic costs. Working alongside our partners (landowners, woodland managers, technological companies and policy makers), Fusion Forest will provide the means to prepare forests for outbreaks ahead of their occurrence, reducing critically mitigation costs. Forecasting pathways of transmission opens the door to new strategies to halt the spread of pathogens, that will no longer be assumed to be inevitable. Combining physical and biological barriers for pathogens in our forests is a ground-breaking idea, and Fusion Forest will generate tools and specific guidance to ensure this synergy.

UKRI Gateway to Research · FY 2025 · 2025-02

3D printing can revolutionise manufacturing by increasing speed at reduced energy input and efficiently using resource-intensive materials. But it is most commonly applied to commodity metals based upon iron (Fe) or aluminium (Al) thus compromising its displacing of more traditional manufacturing routes. Our strategy – underpinning the context of the proposed research – is to target it instead on refractory alloys for which conventional processing – involving casting, forging and subtractive manufacturing – is hampered by their very high (>2000oC) melting points. Refractory metals e.g. tungsten, tantalum and niobium can withstand the challenging environments of ultra-high temperature, the human body or outer space. Here, superior metallic products are needed to support the advanced economies of the UK and Japan, where high-value manufacturing is critical for competitiveness. Examples are plasma-facing components for nuclear fusion reactors, hot sections of thrusters for rockets and human implants.  Through the design of hollow structures, it is even possible to embed further functionalities, such as thermal management, light-weighting, and biocompatibility. Nevertheless, processing-related defects, e.g. cracks and pores, threaten the application of this transformative technology. The proposed research will improve the quality of refractory metal parts by elucidating the fundamental causes of defects and propose pragmatic strategies to mitigate their formation. The key challenge: due to their high affinity for oxygen, 3D printing of refractory alloys can cause embrittlement and hence hamper properties e.g. strength, fracture toughness and ductility. Oxygen pick-up can occur during (i) the powder-making process – its surface area is large – and (ii) additionally the subsequent printing. How to mitigate this risk? Ingenious approaches will be attempted, using insights into the chemical processes at play. Controlling the oxygen level is crucial to enable advanced application of these alloys, since otherwise manufacturing defects such as fissures and cracks arise, caused by large cooling rates and stress build-up by differential thermal contraction. This project’s broad aim is the successful 3D printing of refractory alloys, promoting it as the accepted method for production. We will do this via the specific objectives of (i) elucidating the risk factors for oxygen uptake, (ii) mitigation of them by modelling-inspired approaches and (iii) demonstration of proof-of-concept via the execution of defect-free 3D printing. We are proposing three coherent work packages spanning manufacturing, characterisation and mitigation which utilise unique expertise from UK and Japan partners. We have three major goals: (1) to quantify oxygen intake by different manufacturing routes, including laser-powder bed, electron beam melting, hot isostatic pressing and spark plasma sintering; (2) to understand the oxygen ingress mechanisms and kinetics by multi-length-scale characterisation and computer simulations; (3) to mitigate oxygen by in-situ alloying using getter (sacrificial) materials, nano-particles and as volatile substance, with interaction rationalised by computational fluid dynamics modelling. This work will emphasise consistent powder feedstock, oxidation reactions at crystal defects and effectiveness of mitigation strategies. The project will assist the UK and Japan to increase its competitiveness in the materials sector. This is playing an ever-greater role in low-volume high-end critical applications, promoting widespread societal benefits. The advances made in this project are transformative to a wide range of applications including energy production (nuclear fusion), healthcare (biomedical implants) and telecommunication (satellites). The proposal is timely given the recent energy crisis, ageing society and space technology development. The envisaged translational impact echoes strongly with the UN sustainable development goals.

UKRI Gateway to Research · FY 2025 · 2025-02

Context Female genital mutilation (FGM) is a harmful practice that involves the partial or total removal of external female genitalia for non-medical reasons. It is estimated that more than 200 million girls and women globally have undergone FGM. In the West Midlands, 12-16 of every 1000 women and girls are affected. The practice, which is still rising, has serious health, psychological and social consequences. To raise awareness of FGM and to promote actions that will lead to its prevention, awareness-raising campaigns have been rolled out across the UK. In addition, there is a UK-wide requirement for FGM to be included in all educational settings. If these interventions are to be successful, it is important that the language used is accessible and acceptable to the recipients, including families and community leaders, as this is most likely to promote agency and empowerment, allowing them to make informed decisions and take appropriate actions. Challenge Despite the crucial importance of using the right language, no studies to date have explored the language that is used in educational settings and campaigns relating to FGM, and the impact that it has on its recipients. Nor have there been any investigations into how the efficacy of the language can be maximised. This is important because the lexical and grammatical choices made in crafting messaging in relation to FGM will have powerful consequences for audience interpretations and subsequent actions.

UKRI Gateway to Research · FY 2025 · 2025-02

My lab is focused on understanding the pathogenesis of the invasive fungal infection, cryptococcal meningitis, which was recently named as the number one priority fungal disease requiring urgent attention by the World Health Organisation. Despite that, there is little understood about how immune responses are regulated in the brain during this infection. The major immune cells resident in the brain are macrophages called microglia. It was not clear how these cells responded to Cryptococcus neoformans, the main causative agent of cryptococcal meningitis. It was also not known whether these cells play a protective or deleterious role during infection, since macrophages can act as intracellular infection reservoirs for this fungus, but the relevance of this in the brain had not been studied. We have shown that brain-resident immune cells called microglia are an important reservoir for intracellular fungal infection. Moreover, we have found that microglia are important drivers of heterogeneity within the fungal population by shaping their nutrient scavenging responses, and that these fungal-microglia interactions can be modulated by the protective cytokine IFNg. This is important, because IFNg is a promising immune-based therapy for cryptococcal meningitis and there is significant interest and translational potential in understanding how this cytokine exerts its protective effects in the brain.

UKRI Gateway to Research · FY 2025 · 2025-01

In the current Circular Economy (CE) landscape, many activities fail to fully realise the potential value of products, components, and materials. Rather than being repaired, reused, or remanufactured, a significant number of products end up in mixed waste streams and are recycled, which is the least valuable end-of-life CE option. This leads to a substantial loss of residual value. One of the critical challenges in the CE is the absence of effective and efficient methods for large-scale separation of products, which are in very different used or end-of-life conditions, into various CE options such as reuse, repair, remanufacture, repurpose, or recycle. The presence of mixed waste streams poses a significant barrier to creating tighter loops of circularity and preserving materials at their highest value for an extended period. The current methods of evaluating end-of-life options are inefficient and inaccurate as they heavily rely on human judgment, which is often based on experience and prone to bias and error. Similar to how triage can help create priorities and organisations in healthcare systems, RoboTriage proposes a new concept, circularity triage, referring to the process of rapidly examining products, components and parts to determine their best CE option, e.g. reuse, repair, remanufacture, repurpose, or recycle. We aim to create and develop robotic systems that can perform circularity triage by capturing the health condition data of used products, allowing for a swift evaluation of product conditions so as to group products of similar conditions, avoid mixed waste streams and recommend the highest-value CE options. RoboTriage has five objectives: O1: To create robotic systems that can perform triage operations (at the operation level). O2: To create system intelligence that enables smart planning of triage operations (task level). O3: To identify new patterns and connections between product history data and product conditions using autonomous large-scale robotic triage (task level). O4: To identify value opportunities and develop circular business models with the new patterns and connections obtained to facilitate high-value retention (system level). O5: To support the uptake of CE and sustainability considerations and practices by industrial partners through three flagship case studies. RoboTriage's academic impact transcends the manufacturing and CE domains, extending to ICT, AI, and data science. The influence of RoboTriage extends into economic, societal, and environmental domains. RoboTriage technologies have the potential to be deployed for CE purposes, thereby enhancing their scale and productivity. On average, a one per cent increase in robot density correlates with a 0.8 per cent increase in productivity. The impact of ideas in RoboTriage will be exemplified by our 11 industrial partners and over £700k contributions (including over £400k cash contributions) from the three host institutions and external partners. Facilitated by RoboTriage technologies, the promotion of high-value CE options such as remanufacturing could lead to a 90% reduction in primary material usage and a 55% reduction in energy and emission impact. The impact of this project will extend to international organisations through our United Nations partners, ITU and UNESCO, both of which are also our project partners.