University of Birmingham

UKRI Gateway to Research · FY 2025 · 2025-09

During this 12-month Fellowship, I aim to disseminate my PhD and maximise its impact whilst developing professional and research skills consistent with my agenda of establishing an academic career as a scholar of climate change adaptation. This Fellowship aim will be pursued through the following objectives and activities. Establish academic publication track record: I will write and publish three articles in high-impact journals drawn from my PhD. The first paper on, ‘Interacting gendered institutions’, demonstrates how constraints to women’s climate response interweave with institutions. It contributes knowledge about the complex nature of women’s adaptation constraints and implications for climate response. This paper will be published with the Journal of African Affairs. The second paper on, ‘Negotiating intra-household gender relations’, demystifies the universalisation of women as victims of climate change and shows the significance of women’s agency in climate adaptation. I aim to publish this article with Geoforum journal. The third paper, ‘Feminist Political Ecology (FPE)’, examines FPE’s strengths and gaps in guiding critical institutional analysis. It suggests effective ways of analysing institutions using FPE perspectives. My aim is to publish this paper with the Journal of Feminist Geography. Build networks: To network with academics, I will present two papers drawn from my PhD at two conferences, Development Studies Association (DSA) and Political Ecology Network (POLLEN). Membership in DSA will strengthen my network even after the Fellowship. My research will also be presented at three research meetings, International Development Department (IDD) seminar, Environment and Sustainable Livelihoods (ESL) and Birmingham Institute of Forest Research (BIFoR). The conferences and research groups bring together diverse climate change scholars whom I will interact with, gain constructive feedback and establish potential collaboration opportunities for my ESRC New Investigator grant application and future research. With non-academic audience, I will hold stakeholder workshops with farmers, clan leaders, selected policymakers and practitioners working on climate adaptation and agriculture in Uganda. This will provide space for interacting with stakeholders to strengthen and expand my network, providing a firm foundation for future collaboration. Expand non-academic impact: This will be achieved through two strategies, stakeholder workshops and policy briefs. Workshops will provide space for engaging with climate adaptation policymakers, practitioners and farmers through sharing my research and generating insights for translating it to actionable points to inform adaptation policy and practice. Two policy briefs, recommending strategies for addressing gender gaps in climate adaptation and how institutions can synergistically enhance gender equity in adaptation decision-making will be co-authored with two Community Based Organisations. To further facilitate engagement, the policy briefs will be shared with Uganda’s Ministry of Agriculture Animal Industry and Fisheries, Consultative Group for International Agricultural Research and ActionAid. These agencies will use the briefs to inform practice and integrate the recommendations into climate change policy development processes. The briefs will be published on my website, www.africaclimatehub.com, to engage with a wider audience. Develop research skills: I will undertake training on Social Network Analysis (SNA) using R to further develop skills of analysing institutional interplay and its linkage to climate adaptation, farmers network and gender power dynamics in climate response. The training will also enhance my ability to integrate quantitative research methods in my future research, improving my capacity to write high-quality application for ESRC New Investigator grant about evaluating the effectiveness of forest conservation in moderating climate risks, after the Fellowship.

UKRI Gateway to Research · FY 2025 · 2025-09

There is plenty of evidence for inequalities in physical and mental health. A recent Birmingham City Council (2025) report showed lower healthy life expectancy for women in Birmingham compared to the national average. In addition, the Birmingham Community Health Profile Report showed higher occurrence and severity of poor mental health in ethnic minority communities. To address these inequalities, it is important that behavioural programmes to improve health are tailored to meet the needs of communities who need these programmes the most. Physical activity is a commonly used behavioural intervention to support improvements in physical and mental health. Like poor health, levels of physical activity are not equally distributed in society: people from ethnic minorities, especially women, are less likely to be physically active enough to achieve health benefits. Further, women from ethnic minority communities were deemed to be less active than women of white or mixed ethnic groups (Race Disparity Unit, 2021). Therefore, there is an urgent need to enhance our knowledge on how to overcome the specific barriers preventing women from ethnic minorities from being more physically active. Additionally, to support continued engagement, we need to explore how individual factors influence the outcomes of these programmes. The Warwickshire Cricket Foundation (WCF – the community division of the Warwickshire County Cricket Club) is a dedicated charity that uses cricket to engage and inspire people in Warwickshire to have positive experiences. The foundation runs a range of cricket-based community programmes. Given the low levels of physical activity in women from ethnic communities in Birmingham, WCF has a specific focus on programmes for this population. WCF have recently received funding from the England Cricket Board for the ‘Cricket Cities’ programme to expand their programmes for girls and women from ethnic minorities. The Cricket Cities programme offers novel sessions and events providing a unique opportunity to evaluate a range of community-based cricket programmes for this population. Previously programmes have received positive feedback; however, WCF are aware many women invited do not take up, or complete, the programme. WCF is keen to get a better, evidence-based understanding of the reasons why women do or do not take part, i.e., their barriers and facilitators to participation, as well as identify ways to enhance the effectiveness of their programmes for overall health in this population. Theory (COM-B; Michie et al., 2011; 2014) will be used to guide the development of methods for coaches and WCF to better assist specific aspects of a behaviour to support the needs of women from ethnic minorities within the community. The aim of this fellowship is to develop a toolkit to enhance the uptake of and continued engagement of community-based physical activity programmes to improve health in women from ethnic minorities. This aim will be achieved by the following objectives: 1.     Explore reasons why women from ethnic minorities do, or do not, take part and engage with cricket programs; 2.     Evaluate the effectiveness of the cricket programmes to improve health, and explore individual characteristics that could influence the effectiveness of the cricket programmes; 3.     Co-develop with coaches and participants a toolkit to support women of ethnic minorities to take part and engage with cricket programmes; and 4.     Review and adapt a toolkit for coaches to support continued engagement with sports-based physical activity programmes for women from ethnic minorities.

UKRI Gateway to Research · FY 2025 · 2025-09

A recent £20 million funding announcement by the UK government and newly established Regulatory Innovation Office (RIO) has emphasised the strategic importance of developing drone capabilities in the UK, such as in NHS medical contexts. This follows several trials of drone deliveries of blood, defibrillators and other related materials by NHS and industry partners in UK nations as part of the UKRI Future Flight Challenge – a government and industry-funded innovation programme. The Welsh Ambulance Services University NHS Trust with Snowdonia Aerospace have been making the case for a medical drone network in Wales, and as part of this acknowledges there are potential planning and public perceptibility risks with integrating drone technologies. Building on my PhD, and my postdoctoral research in the ESRC Future Flight Social Science research programme, this fellowship will explore the organisational and public perceptual factors that may shape and influence how medical drone use develops. In partnership with the Welsh Ambulance Services University NHS Trust, I will use a mixed-methods approach to provide behavioural insights into 1) the range of public perceptual and attitudinal factors in different geographical contexts across the Welsh drone network; and 2) the organisational attitudes and behaviours of stakeholder groups as possible enablers or barriers to its integration. The project will combine new qualitative and quantitative data (semi-structured interviews, focus groups, survey) with insights from existing research (nationally representative surveys, qualitative data), to systematically detail behaviours in relation to the barriers, opportunities and risks of medical drones. The multi-disciplinary social science insights generated by this fellowship will further support my engagement with policy makers, regulatory bodies and other stakeholders in this emerging sector.

UKRI Gateway to Research · FY 2025 · 2025-09

Cornea - the transparent front window of the eye - serves as a critical structure to normal vision and ocular surface defence. Damage to the cornea can lead to significant ocular pain and permanent scarring with resultant visual impairment or blindness. Infectious keratitis (IK), or commonly known as corneal infection, is the leading cause of corneal blindness globally. It has caused ~5 million cases of blindness and is estimated to affect ~2 million people each year. Affected patients are usually debilitated by pain and visual impairment, and they often require long-term hospital admissions for intensive antibiotic treatment. However there has been a growing concern on the declining antibiotic efficacy due to emerging antimicrobial resistance (AMR), polymicrobial infection (i.e. infection caused by more than one organism), and limited treatment options. In addition, AMR has emerged as a global health threat and is estimated to cause over 1 million deaths annually. These issues highlight the urgent need for new effective antimicrobial treatment for tackling IK and AMR. Antimicrobial peptides (AMP), or host defence peptides, form an important component of the first-line defence in all living organisms (including human). They are made up of amino acids (the basic structural units of protein) and can be found in various parts of the human body, including the eye. They have recently shown promise as potential treatment due to their unique antimicrobial activity against a wide range of organisms, such as bacteria, fungi, parasites, and viruses. These positively charged AMP usually kill the pathogens by disrupting the negatively charged membrane (outer surface coating) of the organisms. However, the clinical utility of AMP is limited by several issues such as potential toxicity to human cells, instability in certain body environment, susceptibility to breakdown by human / bacterial enzymes, and cost. Recently, I have developed efficacious and safe hybrid AMP, based on rational combination of human beta-defensins (HBDs) and human cathelicidin (LL37), for treating IK. I have also developed highly accurate artificial intelligence (AI) algorithms in predicting the activity of AMP. The overarching goal of my MRC Fellowship is to develop novel AMP for treating a range of IK and tackling AMR, using AI and novel drug delivery systems. During the first stage, I will develop novel peptide language-based generative AI models to help optimise my human-derived hybrid AMP and potentially discover new AMP. I will then test the antimicrobial activities, safety and mechanism of action of the improved AMP against a range of bacteria and fungi related to IK and AMR, through both laboratory and ethically designed animal studies. In the second stage, I will explore various formulation strategies to enhance the efficacy, safety and stability of my AMP, using novel fluid gel technology (Gellan) and biodegradable nanoparticles/polymers. I will perform a series of experiments, including laboratory and animal experiments, to characterise and examine the properties, efficacy, safety and stability of my formulated AMP. These represent the essential steps before advancing the AMP therapy to human clinical trials. The proposed experiments will be conducted collaboratively in the UK, the US, and Singapore. Successful development of these AMP can bring new exciting therapies to the clinic, ultimately benefitting patients with ocular and potentially non-ocular infections. This may also offer a potential novel solution to AMR.

UKRI Gateway to Research · FY 2025 · 2025-09

A major challenge of modern life is how we can live in cities healthily, happily and sustainably, with over half the world's population now living in urban areas. Housing design and development can be used as a routed to reimagine urban life for human and planetary well-being. This project, through collaboration with a housing association – J49 Ltd – as the partner organisation, aims to unravel the interactions of housing design with human behaviour. A recent novel concept, urban plasticity – the ability of a city to undergo structural and functional change as a result of interactions between people and place, will be applied to used to achieve two key aims. The first aim is to understand how place design, particularly housing, can shape behaviour. This aim will draw on and advance the urban plasticity framework as a way of explaining urban life as people-place interactions using neuroplasticity and urban resilience research. The second, translational aim is to encourage design professionals to use behavioural research to inform place design. Integrating an understanding of human behaviour into the design process is an important way to guide the focus of housing design and development away from profit and back towards human and community flourishing. These aims will be achieved through forming connections between academia and industry partners using workshops and community engagement events, conducting interviews with design professionals and residents of J49's developments, written outputs in academic and non-academic formats. Finally, the fellowship will cultivate an attentiveness as a behavioural researcher to the interactions of behaviour and place for the research fellow with a background in psychology but a keen curiosity for urban design. The programme will culminate in further funding applications and a new research agenda aimed at the reconnection of person and place for collective flourishing.

UKRI Gateway to Research · FY 2025 · 2025-09

Weight is at a premium for aerospace applications. Innovations have been driven to reduce the weight of engines for fuel saving, such as Rolls-Royce’s honeycomb fan blade and GE’s composite fan case. A jet engine is made of one tonne of high-density heat-resistant superalloys. However, they are necessary because higher temperatures give higher thermal efficiencies in propulsion. This research aims to produce lightweight high-temperature structures by introducing porosity to non-critical load-bearing parts thus reducing their relative density. Given the importance of lightweighting, it might even be possible to make them float. Hollow superalloys exist, but they are not intricate and limited by casting precision, the finest cavities are a few millimetres requiring extensive chemical leaching afterwards. Fortunately, recent ground-breaking developments in 3D-printing make crack-resistant superalloys manufacturable from powder of a diameter less than that of human hair. Thus far, research on metal 3D-printing has heavily concentrated on consolidating powder to 100% density. Yet, porous materials can be adopted with cellular (cavity) sizes more than ten times finer than casting. Each cell is a building block, it has struts or surfaces that can be designed to deform under stretch, bend or shear mode. Thus, enabling the engineering of microscopic cellular structures, we can manipulate their macroscopic behaviour. This class of materials is known as architected materials, widely researched, but only at room temperature. Understandably hindered by available heat-resistant materials. But the deformation behaviour and mechanical properties – particularly in extreme environments – need to be proven and it is aimed to do this here. This research will leverage the advances in superalloys 3D-printing and architected materials – a new interdisciplinary subject. We will concentrate on using new generations of printable superalloys designed specifically for 3D-printing. My preliminary results, for example on the architected superalloy ABD-900AM, have illustrated unexpected embrittlement and pronounced asymmetry in micro- and macroscopic mechanical behaviour at high temperatures, attributed to operative damaging routes. By understanding their mechanisms, we can possibly decode unnatural behaviours as seen in the room temperature counterparts, such as tuneable thermal expansion or ultra-damage tolerance. The proposed work will determine the causality by studying microscopic deformation modes under hinging and buckling as well as accounting for various damage mechanisms including plasticity, creep relaxation and oxidation. Necessary new knowledge must be generated to better manipulate the distribution and orientations of the constitutive structural units, so they are mechanical sound at elevated temperatures. This work is comprised of cohesive work packages spanning design, manufacture, testing and modelling. We have two major goals: (1) to understand the deformation and fracture of architected materials with experimental evidence from loading under extreme conditions and (2) to create high fidelity models (focusing on finite element based) that accurately describe and predict their behaviour. We will initially focus on idealised simple structures (honeycomb and truss-lattices) and then extend to stochastic structures with non-repeating units (Voronoi). This work will emphasise the effect of work hardening/softening, strain-rate sensitivity and influence of oxidation. This work will help the UK to increase its competitiveness in the booming 3D-printing market which is estimated to be £15bn. The sector has played an increasingly important role in recent years in derisking supply chain issues via localised materials supply, logistics and manufacturing. It would also reinforce the UK’s global leadership in several high-tech sectors such as aerospace, satellites and orthopaedics.

UKRI Gateway to Research · FY 2025 · 2025-08

The ~2 metres of DNA found in each of our cells can only be fitted into the nucleus through significant compaction, which is done through interactions with nucleosomes. The compacted DNA/nucleosomes, known as chromatin, is regulated through epigenetic modifications: posttranslational modifications on histone proteins as well as the DNA itself. Every time a cell divides, it has to first duplicate its genome. To do this, the chromatin must be dismantled before the replication fork, and reassembled after replication fork passage. Faithful replication of the genome and epigenome is key for normal cell proliferation, cell identity and healthy organism growth. The restoration of chromatin features is directly coupled to the process of DNA replication. Immediately behind the DNA replication fork a number of processes must happen: - DNA synthesis is completed through joining together of the short Okazaki fragments (OF) synthesised on the lagging strand, - the parental histones are transferred and deposited onto both daughter strands and newly synthesised histones incorporated, - newly synthesised unmethylated DNA strands are appropriately methylated, - the daughter strands are held together by cohesion molecules, so that they can be separated later in mitosis. We currently lack understanding of how these “behind-the-fork” processes are coordinated in time and space to efficiently deliver chromatin replication.   Using the cell-free Xenopus laevis egg extract system, we have discovered that the UHRF1 ubiquitin ligase, which is known to be essential for maintenance of DNA methylation during DNA replication, is also important for execution of other aspects of chromatin replication, specifically the maturation of OF and new histone deposition. We have also shown that in human somatic cells UHRF1 has an essential, yet uncharacterised, role in S-phase progression. Our hypothesis is that UHRF1 acts as a coordinator of chromatin replication processes, so by understanding how UHRF1 acts in these processes we will shed light on their cooperation “behind-the-fork”. The Xenopus laevis egg extract system is an early embryonic system and allows for studies of synchronous DNA replication in the absence of transcription. This reductionist system allows studies of the direct replication-related consequences of UHRF1 depletion without the confounding effects of hypomethylation. Importantly, DNA replication in egg extracts is regulated very similarly to somatic cells; many fundamental discoveries within the DNA replication field were first made using this system. Through a combination of analyses in Xenopus egg extracts and in human immortalised cell lines, in which we can rapidly degrade degron-tagged UHRF1, we aim to understand: (i) what the consequences are of UHRF1 depletion, and characterise its functions during DNA replication independently of DNA methylation activity. (ii) how UHRF1 regulates OF-maturation and chromatin re-establishment, to shed light on the mechanism of UHRF1 function and the coordination between these “behind-the-fork” processes, and (iii) the differences in chromatin reconstitution dynamics between leading and lagging strand of replication fork and whether UHRF1 activity is needed equally on both strands.   UHRF1 is overexpressed and serves as an oncogenic driver in multiple cancers, with significant potential as a therapeutic target and/or cancer biomarker. Our project, although aimed at understanding of fundamental rules of chromatin replication, will help to realise this therapeutic potential of UHRF1 by characterising its functions which are essential for cell proliferation and affect human disease development and healthy aging.

UKRI Gateway to Research · FY 2025 · 2025-08

Primary biliary cholangitis (PBC) is a lifelong autoimmune disease affecting around 22,000 people in the UK, 90% of whom are women. Autoimmune diseases like PBC arise from aberrant immune responses, leading to organ damage. In PBC, the immune system’s T cells target and attack the liver’s bile ducts, leading to progressive bile duct injury and liver scarring, preventing bile drainage from the liver and causing symptoms of itch, fatigue and jaundice. The only available treatment for PBC is ursodeoxycholic acid. Another drug, obeticholic acid, was introduced but was withdrawn in June 2024 by authorities due to a lack of efficacy. Both drugs target bile acids, rather than the underlying autoimmune cause. Unfortunately, only 60% of patients respond to present treatments, leaving patients susceptible to an increasingly intractable itch and profound fatigue, impacting daily activities and eroding quality of life. As PBC progresses, a liver transplant becomes necessary. Autoimmune liver diseases like PBC now make up over a quarter of liver transplants, an already scarce resource. Even then, in over a third of patients, PBC recurs, necessitating re-transplantation. Normally, regulatory T cells (Tregs), another kind of immune cell, protect against autoimmune attacks like that seen in PBC. Tregs educate the immune system to stop and prevent autoimmune attacks. Infusing Tregs has even been shown to treat PBC in mice, returning them to health. Many have tried to use Tregs to treat various human autoimmune diseases. However, there are few Tregs in human blood, and when grown in the lab, Tregs can be unstable, making their manufacture challenging. Due to this, to date, Tregs have not shown efficacy as a treatment for human autoimmune diseases. Having first discovered Tregs in 1995, Shimon Sakaguchi’s laboratory published a new method of Treg generation in 2019, producing stable, highly functional Tregs (SFiTregs). This method generates large numbers of cells in a short period. Last year, I spent three months in Shimon Sakaguchi’s laboratory, learning this novel technique and generating SFiTregs from the blood of PBC patients, becoming the first to generate SFiTregs for application in human disease. Through this fellowship, I will generate SFiTregs and investigate their efficacy and function in PBC. As Europe’s largest solid organ transplant unit, we receive a large number of livers for research, including approximately 30 PBC explants per year, made available through established ethics. Perfusing PBC livers with generated SFiTregs, I aim to observe their migration and localisation using microscopy, determining the ability of SFiTregs to reach the site of tissue damage in PBC. I will also explore whether SFiTregs can survive and function in inflammatory environments and examine whether they can prevent bile duct damage. This will be done through cell culture experiments with fresh human liver cells from our transplant programme. By conducting the above work, I aim to demonstrate a novel, superior method of Treg generation with utility in PBC, a typical autoimmune disease. This would introduce a new therapeutic option for PBC, relieving patients from a poor quality of life hampered by intractable itch, fatigue, jaundice, and the need for transplantation. Success in the project would pave the way for further application of SFiTregs. Both organ transplantation and autoimmune diseases are in need of new, effective treatments, and with this project’s success, we may see a new era in immune therapies, defined by SFiTregs.

UKRI Gateway to Research · FY 2025 · 2025-08

Technologies based on electrochemical flow systems are emerging as promising more-sustainable solutions for the global challenges of climate change, materials availability and clean water supply. They offer opportunities to meet the goals of the UK’s “Net Zero” strategy, through development of improved energy storage and improved electrochemical recycling of mineral and water resources. Electrochemical flow technologies are underpinned by a common operational mechanism, where performance is simultaneously governed by electrochemistry and hydrodynamics (flow, diffusion and convection), and share common electrochemical processes, that establish internal concentration gradients which are coupled with mass transport. While there is increasing interest in developing electrochemical flow technologies, their advancement, and ultimate commercialisation, is inhibited by a lack of understanding of the fundamental processes controlling them, limiting their improvement, optimisation and ultimately, their commercialisation. In this project, we will develop advanced characterisation techniques, based on magnetic resonance imaging (MRI), to non-invasively, holistically and simultaneously observe and quantify the interplay between electrochemistry and flow for the first time. These characterisation techniques will enable direct and simultaneous identification and localisation of species and depletion/reaction zones, while mapping diffusion and flow velocities of electrolytes/electrodes, in multivalent metal ion flow batteries, redox flow batteries and flow-electrode capacitive deionisation. The proposed project will design, construct and optimise flow cells and establish a suite of imaging protocols to study electrochemical flow systems. The development of these cells and imaging protocols will be guided by a range of test systems, pioneered by researchers developing electrochemical flow technologies. Systems will be selected, initially, from amongst those studied by our project partners, but will extend to systems beyond these, which are being advanced by researchers in the wider community. This project will deliver transformative insight into the behaviour and optimisation of a range of electrochemical flow systems, leading to an acceleration of their development. Our initial focus will be on redox flow batteries, multivalent metal-ion flow batteries and flow-electrode capacitive deionisation. However, the goal of the proposal is to not only advance these initial systems/technologies, but to develop the characterisation tools required to advance all electrochemical flow technologies. Our methods will be applicable to a diverse range of electrochemical storage systems, as well as electrochemical recycling of metals and other critical elements/materials, organic electrosynthesis and flow synthesis. Working with our project partners, we will ensure the MRI technique developments are guided by the applications. Building on the network of electrochemical researchers established in this project, we will engage with the wider electrochemistry, energy storage and sustainability communities, disseminating technical and scientific knowledge, and ensuring these techniques become more widely employed and accessible beyond the NMR and MRI communities. Therefore, this project will enable the establishment of novel operando flow cells and imaging protocols to advance our understanding of all electrochemical flow systems, the acceleration of technological innovation of electrochemical flow technologies through greater understanding of the fundamental molecular processes underpinning these more-sustainable electrochemical applications for the future, the creation of a national network of researchers developing electrochemical flow technologies, accelerate the UK's progress towards New Zero.  

UKRI Gateway to Research · FY 2025 · 2025-08

The prototypical question in Ramsey theory asks how large a mathematical structure must be in order to guarantee a particular type of pattern emerges. For example, a special case of Ramsey theory for graphs can be rephrased as follows: in any party of six people there is always a set of three people who know each other or a set of three people who do not know each other; note, this is not true in general for a party of five people. Ramsey-type results occur in a wide range of settings, including in Graph Theory, Number Theory and Theoretical Computer Science. In recent decades, there has been significant interest in the typical Ramsey properties mathematical structures of a given density possess. Whilst there have been several recent breakthroughs in this area for specific mathematical structures, there is still a need to develop general approaches that are applicable to a wide variety of settings. The aim of this project is to capitalise on the personal momentum of the PI to develop such general approaches in arithmetic settings. The initial phase of the project will concern arithmetic progressions in the prime numbers, before moving on to consider Ramsey properties of collections of whole numbers more generally. Progress on these topics will then be used as a spring-board for studying analogous questions in the wider setting of abelian groups. The project will study the combinatorial essence of these problems from Algebra and Number Theory. Indeed, these questions will be attacked by transforming them into problems concerning mathematical networks, specifically, hypergraphs. Our methodology will demonstrate that, as long as so-called supersaturation occurs, one can strip back the arithmetic structure in sets of integers or abelian groups, and instead simply consider the corresponding hypergraph problem. Thus, a long-term aim of the project is to provide researchers in these areas with the combinatorial tools needed to attack such questions.

UKRI Gateway to Research · FY 2025 · 2025-08

Context The challenge of climate change coupled with a growing global population demands that farmers do more with less; agricultural outputs must double by 2050 to mitigate growing food insecurity. Plant diseases account for almost 40% of all crop losses annually, yet we still do not fully understand how plants perceive and respond to pathogens. Plants possess a form of native immunity called Pattern Triggered Immunity (PTI). Activation of this immunity promotes survival against pathogens in the short term, but interestingly also in the long term. Furthermore, PTI can be enhanced (i.e. "primed"), through mechanisms that remain unclear. The challenge this project addresses Emerging evidence shows that plants integrate lasting adaptive responses (i.e. memory) to their environment by altering the accessibility of their DNA, in a process called chromatin remodelling. The extent to which chromatin remodelling integrates a memory of PTI is largely unknown. This proposal will fill this knowledge gap by describing a novel chromatin-based mechanism that primes PTI by allowing plants to ‘remember’ previous infections. Aims and objectives In previous work I showed that a plant chromatin remodelling complex, known as the Polycomb Repressive Complex 2 (PRC2), regulates growth and flooding stress tolerance in the model species Arabidopsis thaliana. I showed that a plant-specific subunit of this complex (called VRN2) directly senses and transduces environmental stimuli to facilitate stress adaptation and survival. In unpublished work I have now shown that the PRC2 also senses pathogens - my preliminary data has revealed that VRN2 is stabilised when PTI is activated and also influences pathogen-associated gene expression. I propose that the VRN2 sensor subunit acts as a previously unknown link between the perception of pathogens and the induction of immediate and long-term survival responses. Using a range of physiological, molecular, and omics-based workflows that I have established, I aim to define VRN2 as a novel pathogen sensor and evaluate the impact of the PRC2 on plant immunity and priming responses. I will achieve this by addressing three objectives: Objective 1: Show that diverse biotic factors influence the stability and makeup of PRC2, and assess how it contributes to defence responses. Objective 2: Use genome-wide sequencing to understand how PTI-triggered stabilisation of VRN2 influences chromatin structure and gene expression. Objective 3: Examine how PRC2 imprints a memory of biotic stress that primes future immune responses and investigate its potential as a point of crosstalk between biotic and abiotic stress responses. Potential applications and benefits This work will reveal a novel mechanism that allows plants to sustain long-term resistance to disease by remembering previous pathogen encounters. Our crops face a barrage of biotic and abiotic stresses that restrict their fitness and yield. Climate change will drive the frequency and intensity of these stresses to greater extremes. Enhancing our knowledge of plant immunity will help to alleviate this by facilitating the development of more resilient crops and providing new disease management strategies. My work is poised to answer fundamental questions about how plants sense and remember interactions with pathogens. This will have broad implications on how we think about crop species, which constantly interact with microbes in the soil and air. This knowledge will inform agricultural policy writing and breeding strategies. Ultimately, this work has the potential to provide new targets for mitigating crop losses, benefiting both society and the economy.  

UKRI Gateway to Research · FY 2025 · 2025-08

Context and current state-of-the-art: This co-created, business-inspired, fundamental research aims to enable Tokamak Energy Ltd (TE) to develop and improve fusion reactor centre-column designs by understanding the effect of irradiation, intense plasma-exposure and high-heat flux (HHF) on advanced shielding materials degradation. This partnership, with a long-term vision of contributing to fusion commercialization efforts, will be delivered in active collaboration with world-leading fusion centres in the EU, and further guided by a steering committee comprised of subject-matter experts from the US and the UK. Meeting net-zero emissions by 2050, as outlined by the Net Zero Government Initiative, requires green innovation technologies such as fusion energy which promises carbon-free, safe, secure and abundant power. The UK-based TE aims to demonstrate commercial fusion in the 2030s by combining its spherical tokamak design with rare-earth barium copper oxide (REBCO) high-temperature superconducting magnet technology, thereby, opening a pathway for smaller more compact power-plants. Key to success is a robust “centre-column” design, a life-limiting component comprising of REBCO coils. However, these magnets are highly susceptible to radiation damage and heat. Smaller power-plants offer limited shielding volumes, necessitating high-performance advanced shielding materials, with a thorough understanding of their fusion-relevant in-service degradation phenomena. This is critical to enabling TE’s commercial spherical tokamaks. Key Challenge: Fusion in-vessel conditions are severe – high neutron bombardment (>100 displacements per atom, dpa), a wide temperature range (cryogenic in magnets to >1000 °C), intense plasma particle exposure (>1019 ions.m-2.s-1 of D,T, He, impurities etc.)  and HHF (tens of MW/m2 to several GW/m2 during disruptions). Given these synergistic challenges, the primary shielding candidates for TE’s centre-column are novel ceramic shielding materials: reduced-activation binder tungsten carbide (rab-WC) and di-tungsten pentaboride (W2B5), which are protected by potassium doped tungsten (K-doped W) in the plasma facing regions. Shielding failure in-service would result in failure of the centre-column. But little is known regarding in-service degradation of these materials, over their wide envisaged operating temperature range from cryogenic to >750 °C, which is a major design-limiting challenge. Project Aims/Objectives: To make progress towards the overarching goal, the following short-term objectives, to be completed within three years, are proposed: Understanding radiation-induced degradation of ceramic shields from cryogenic to 800 °C (rab-WC, W2B5). Quantifying the effect of plasma exposure and HHF on K-doped W and rab-WC. Preliminary HHF testing of W-WC joints. Baseline neutronic and Multiphysics assessment of damaged shielding materials to guide a preliminary centre-column design using data from (i), (ii) and (iii). Applications and Benefits: By enabling TE to develop robust fusion in-vessel component designs guided by materials degradation knowledge, this study will (i) enable the UK to be a global leader in the technologies needed to decarbonise our economies and transition to net zero, and (ii) directly support the UK’s plan for bringing about a Green Industrial Revolution by commercializing fusion energy technology. By building partnership with the University of Birmingham, which has notable fusion materials expertise, and coinvesting in discovery science and engineering, TE stands to become a world-leader in fusion energy, placing the UK at the forefront of the fusion landscape and benefiting the wider UK economy.

UKRI Gateway to Research · FY 2025 · 2025-07

MIGDIPLO investigates how states use cross-border mobility as an instrument of foreign policy. It extends the concept of "migration diplomacy" to analyse the strategic linkages between international mobility and interstate relations. Drawing on fieldwork and comparative case studies across Asia and the Middle East, the project examines how governments cooperate or exert pressure through migration-related tools, including labour agreements, visa regimes, and refugee hosting. By mapping the global politics of migration diplomacy, the research offers new insights into statecraft, power asymmetries, and the international governance of human mobility.

UKRI Gateway to Research · FY 2025 · 2025-06

ERD-NIP aims to establish a conceptually coherent and philosophically rigorous view that makes sense in a global, diverse society, by defending cognitive and dispositional aspects of religious belief, and Islamic belief in particular, while emphasizing its compatibility with epistemic and salvific inclusivism. ERD-NIP addresses the issue of what kind of religious epistemology would better ground the rationality of religious belief. It aims to develop a tenable religious epistemology as a midway between theistic evidentialism and reformed epistemology based on Thomas Reid's moderate foundationalism. However, the main breakthrough of ERD-NIP is to take the discussions to an Islamic context by developing the Reidian alternative religious epistemology based on an Islamic perspective and by offering an Islamic response to religious diversity on this epistemological ground in light of the following research questions: What is the connection between reason, belief, and revelation in Islam in forming one's religious attitude and judging the truth of Islamic beliefs? Which approaches to religious epistemology can be identified in the Islamic tradition as corresponding to contemporary theories and to which extent do they fall short of grounding the rationality of religious belief? How can we develop a new Islamic theory to ground rationality of religious belief in the most satisfying way? What kind of response can this new theory offer to religious diversity as a midway between religious pluralism and exclusivism? How can this new Islamic theory accommodate epistemic and salvific inclusivism without opposing the principle of logical contradiction? ERD-NIP aims to establish a rational Islamic epistemological foundation to respond to religious diversity from an Islamically inclusivist perspective, by a thorough analysis of the Islamic sources and bringing them into conversation with the conversation with the contemporary philosophy religion discussions.

UKRI Gateway to Research · FY 2025 · 2025-06

Nuclear fusion, Generation IV fission reactors and aerospace gas turbines are critical to our future energy generation and transportation. Their operation at high temperatures necessitates construction from a variety of advanced materials. In order to withstand these extreme environments materials require high melting points, high temperature strength and environmental resistance, and, for nuclear, irradiation resistance. There are strong environmental and economic incentives to yet further increase the temperature capability of the materials used, in order to improve efficiency to reduce fuel use, as well as for improve performance, design life and safety. However, while iterative improvements are being made year on year the temperature gains are becoming ever harder to realise. In this Future Leaders Fellowship a step change in temperature capability is sought by the realisation of a new class of body-centred-cubic (bcc, an atomic crystal structure) superalloys based on (1) Tungsten, (2) Titanium, and (3) Steel, for the extreme environments of nuclear fusion and gen IV fission reactors as well as aerospace gas turbine engines. I have created a close network of industrial, national and international academic partners, that will enable translation of these advanced materials from concept through to scale-up. The collaborations will be split across the bcc-superalloys Work Packages: (WP1) Tungsten, linking in UKAEA, toward nuclear fusion and Gen IV fission; (WP2) Titanium, for aero-engines, working with Rolls Royce and TIMET; (WP3) Steels, part of a collaboration with UKAEA, Bangor University and University of Manchester. Bcc superalloys comprise a metal matrix, where the atoms are arranged in a bcc crystal structure, which are reinforced by forming precipitates of high strength ordered-bcc intermetallic compounds (e.g. TiFe or NiAl). This has parallels to the strategy used in current face-centred-cubic (fcc) nickel-based superalloys. However, changing the base metal's crystal structure, and therefore also the reinforcing intermetallic compound, represents a fundamental redesign and necessitates the development of new understanding. The key advantage of using a bcc refractory-metal-, titanium-, or steel- based superalloy is their increased melting point(s), which give the possibility of increased operating temperatures, as well as greatly reduced cost for the case of steels. However, the change in crystal structure requires a fundamentally new design strategy. While the limited investigations into bcc superalloys have indicated that they have attractive strength, and creep resistance, they have been held back by their low ductility. During this fellowship, I will thoroughly investigate multiple ductilisation strategies on bcc-superalloys to advance their technology readiness level (TRL) and so remove the current barrier to their commercialisation.

UKRI Gateway to Research · FY 2025 · 2025-06

In our current moment of extraordinary ecological and economic challenges, there is a global search for alternatives to models of extractive capitalism. While these alternatives offer critiques of the global reach and power of modern economic processes, they are often profoundly local in their application, such as housing collectives, agricultural cooperatives, or alternate forms of energy provision. These schemes, while seeking to create alternate spaces of cooperation and community, have resided alongside or in opposition to global capitalist formations, with particular local repercussions. We define these as ‘sites of fracture’, where messy, complex interactions between global capitalism and local alternative forms of organisation existed and produced particularly rich seams of memory and evidence. Ireland is understood by many measures to be one of the most globalised economies in the world, and is also a place where ownership of land has had profound political and cultural power. It is an ideal case study for exploring histories of capitalism and developing new place-based tools to understand and share this history. This project will explore the history of two Irish ‘sites of fracture’ located at Killeagh Co. Cork (WP1) and Ballyragget Co. Kilkenny (WP2), to record this history and scope its archival trace. Through site visits and community workshops in partnership with artists and local stakeholders we aim to develop a new method of collaborative and situated research to understand and share the layers of global, local, and more-than-human experience of capitalism and its alternatives over the course of the twentieth century. Our aims are threefold. First, we will expand the archive available to scholars and communities interested in investigating Irish economic and environmental history. Our workshops will foster a network of archivists charged with the care of uncatalogued and at-risk archival material and lead to further work to preserve and interpret that material. Second, in collaboration with local artists, we will develop richer expressive tools in the form of deep mapping for local communities to engage with their own histories of life at sites of fracture. Finally, we will develop new methods drawing on the local landscape to expand our resources for exploring these histories in order to chart and assess the collisions of human and more-than-human aspirations in sites defined by globalised extraction. Through the exploratory pilot work proposed here, we aim to develop and demonstrate the value of the ‘sites of fracture’ framework and our novel methods of collaborative engagement with landscapes and community to global histories of capitalism. Our project will benefit local communities through increased access to archival resources and through new forms of artistic expression. It will create expanded resources and frameworks for the study of economic and environmental history. We will make our results accessible to fields beyond Irish studies through two means. First, we plan an international conference on the concept of sites of fracture that will foster dialogue between our Irish research and other global cases. Second, our project will result in two articles and a book presenting its findings and methodological approaches.

UKRI Gateway to Research · FY 2025 · 2025-06

JWST is revolutionising the study of giant exoplanet atmospheres, and recent observations have allowed unprecedentedly precise measurements of their chemical compositions and thermal structures. In particular, thermal emission measurements of these exoplanets are extremely sensitive to their physicochemical properties. In contrast to other techniques such as transmission spectroscopy, thermal emission observations are not significantly inhibited by stellar contamination effects and clouds/hazes. However, current models are not sufficient to interpret the high-precision emission observations of giant exoplanets made possible by JWST. These spectra are sensitive to 3D effects, which can in turn bias atmospheric inferences unless correctly modelled. Indeed, the analysis of some initial JWST datasets has been limited by model uncertainty, highlighting a critical need for improved models to capitalise on the 3D information in these rich datasets. In this STFC project, we will investigate and develop methods to extract accurate and multidimensional information from emission spectrum observations of giant exoplanets with JWST. Our first objective is to test a hierarchy of multi-dimensional atmospheric retrieval models against real and simulated JWST observations, assessing the degree of multidimensionality required when interpreting observations in different thermal and chemical regimes. In particular, we will investigate different parameterisations for inhomogeneous dayside temperature profiles and varying-with-depth chemical abundance profiles. Our second objective is to develop a novel atmospheric retrieval method tailored to eclipse mapping observations. This method will map variations in chemistry and vertical temperature profile across the daysides of giant exoplanets. We will build on an existing eclipse mapping algorithm, 'Eigenspectra', which is able to identify distinct regions of the planet which have similar spectra. We will develop atmospheric retrieval models which account for the relevant geometric factors in order to measure the atmospheric compositions and thermal structures of these regions across the planetary dayside. Modelling 3D effects in giant exoplanet atmospheres is essential in the era of JWST. The proposed work will unlock the full potential of these groundbreaking observations, revealing new insights into the atmospheric physics of giant exoplanets.

UKRI Gateway to Research · FY 2025 · 2025-06

ReCharged is a transformative project that has the vision to develop a new integrated framework toward a practical visualisation platform in order to optimise and streamline climate resilience and whole-life carbon emission assessments for interdependent Transport and Energy Systems, Lifelines and Assets (iTESLA). To achieve this, ReCharged harnesses the power of digital technologies and data to quantify the functionality and recovery of iTESLA after hazards. This is in response to the lack of methods of assessment and communicable visualisations of consolidated climate resilience and whole-life carbon emission metrics for iTESLA. ReCharged will account for interdependencies that lead to failure propagation in transport and energy systems, to accelerate post-hazard recovery, mitigate losses and societal ramifications due to climate change. In doing so, ReCharged underpins synergies and participatory decision-making to combat siloed thinking in infrastructure management. This project will lead to 50% faster decision-making in iTESLA management, 50% reduction of carbon emissions for the two case studies analysed, create new jobs, and make Europeans fit for the Digital Age. ReCharged is a synergy that combines the exchange of interdisciplinary knowledge and tailored training of staff, through an alliance between leading academic institutions, industrial partners, SMEs, and a research and technology center. All beneficiaries are committed to exploiting and transferring their skills and knowledge, to incentivise data-driven resilience toward climate adaptation and reduce emissions in critical infrastructure. ReCharged will augment researchers' skills and career perspectives, create a community of practitioners, improve critical infrastructure, and ultimately make people feel safer.

UKRI Gateway to Research · FY 2025 · 2025-05

Radiotherapy works by inducing irreparable damage into the DNA of tumour cells, which triggers them to die. Significant advances in radiotherapy have been made towards being able to specifically target a tumour with radiation whilst reducing the harmful effects on the surrounding normal tissue. Nevertheless, there are a growing number of genetic factors being identified that influence the effectiveness of the radiotherapy or even prevent its use as an anti-cancer treatment altogether. One of these genetic factors is an inherited hypersensitivity to radiation, which is caused by mutations in specific genes involved in repairing radiation-induced DNA damage. Often, individuals that have inherited mutations in DNA repair genes are highly prone towards developing tumours. However, since every cell in the affected individual’s body is exquisitely sensitive to radiation, the unrepaired DNA damage induced by the radiotherapy would trigger life-threatening amounts of cell death. Consequently, it is imperative to identify tumour-prone patients who have an inherited genetic defect that compromises the repair of DNA damage-induced by radiation, such that alternative treatments can be used to prevent unforeseen therapy-related death. Several rare, cancer-prone syndromes are known to be caused by mutations in specific DNA repair genes e.g. Ataxia-Telangiectasia or Nijmegen Breakage Syndrome. However, affected individuals are usually identified before cancers develop due to the presence of other clinical symptoms, such as small head/brain, dwarfism, recurrent infections or problems with balance/walking. Thus, if cancer develops in these individuals then radiotherapy is avoided. Despite this, new DNA repair genes are constantly being identified. However, whether they are linked to human disease and cancer development or cause a life-threatening sensitivity to radiotherapy if mutated is unknown. In this respect, we have identified a new DNA repair gene called DIAPH1, that is mutated in a previously undiscovered syndrome associated with cancer development and an increased sensitivity to radiation. The function of DIAPH1 is to aid the formation of actin chains in the cell, which are usually important for controlling cell size, shape, movement and division. However, our preliminary data would suggest that DIAPH1 and actin are also important for repairing DNA damage, but how this occurs is not understood. Based on this, the focus of this project is to understand how DIAPH1 and actin control DNA repair with the aim of identifying cellular defects that may contribute to the development of disease. This will be achieved via three main objectives: Investigate how loss/mutation of DIAPH1 affects the capacity of cells to repair DNA damage induced by radiation. Investigate whether DIAPH1-dependent DNA repair is linked with its ability to promote the formation of actin chains. Investigate whether loss/mutation of DIAPH1 and actin also increases the sensitivity of cells to chemotherapeutic agents that block the ability of cells to copy their DNA. The overall outcome of this project is to define the cellular defects arising from loss/mutation of DIAPH1 to allow better clinical management of disease and to prevent adverse side effects associated with treating affected patients that develop a tumour with radio/chemotherapy.

UKRI Gateway to Research · FY 2025 · 2025-05

The formulated product sector influences many aspects of everyday life.  For example, the sector is responsible for producing food and drink, personal-care products, cosmetics, washing and cleaning products, and medicines.  Due to the wide scope of the formulations sector, it contributes a staggering £142bn (GVA) to the UK economy each year.  However, in response to societal changes, there is a growing shift in the sector towards the rapid development of smarter, greener, and more personalised products. This includes: Developing high-quality, nutritious, and sustainable foods that reduce fat and sugar use without compromising the flavour and texture profiles demanded by consumers. The rapid formulation of medicines, therapeutics, and foods to provide cost-effective and personalised products to different age/health groups, e.g. creating personalised nutrition for diabetics. Reformulation of existing products to incorporate new ingredients in response to regulatory changes or shortages, or to avoid degradation due to time in storage. Unfortunately, the UK formulations sector is ill-prepared to deal with these changes.  Innovation is limited by lengthy and expensive development cycles that rely on experimental trial-and-error.  Moreover, the science behind formulated products is complex and under-developed, and advancements require expertise that spans multiple disciplines.  To make matters worse, there is a lack of knowledge exchange across different application areas, leading to duplicated efforts and unsolved problems. It is striking that the underlying challenges across different industrial spaces (e.g. food and drink, pharmaceuticals, consumer goods) are very similar from a mathematical perspective. They all require new, predictive models that can link the processing and microstructure of formulated products to their final function and performance.  Multi-scale mathematical methods applied to fluid and solid mechanics, and heat and mass transfer are the ideal foundation to build such models. Our central aim is to accelerate progress in this key UK sector by creating a long-lasting, multi-disciplinary network with mathematics at the heart that connects academics from multiple disciplines, including engineering, computer science, physics, chemistry, and biology with industrial partners from companies of all sizes, from micro-SMEs to multi-nationals. Mathematics will provide the underlying frameworks for developing predictive modelling capabilities that will unlock innovation across the sector. These models will, for example, open the doors to engineering the taste, feel, and texture of formulated products by varying individual ingredients or processing parameters, with limited need for trial-and-error experiments or even eliminating them altogether. A variety of events to seed collaborations using tried-and-test formats will be organised, and pump priming funding will be made available to develop multi-disciplinary collaborations. A new, community-led network of Innovation Research Fellows will be formed to translate mathematical outputs into impactful deliverables over the lifetime of the NetworkPlus and beyond.        

UKRI Gateway to Research · FY 2025 · 2025-05

NanoBNFix aims to address the global challenge of food security and environmental sustainability by enhancing biological nitrogen fixation (BNF) in soybeans, a crucial process that provides these plants with essential nitrogen nutrients. BNF involves the conversion of atmospheric nitrogen (N2) into ammonia by nitrogenase enzymes found in symbiotic microorganisms known as rhizobia. This natural process reduces the reliance on chemical fertilizers and minimizes the environmental impact of agriculture. While various strategies, such as gene editing, have been explored to improve soybean BNF efficiency, their practical application has been limited. NanoBNFix proposes an innovative approach by harnessing nanotechnology to enhance BNF. Specifically, the project proposes to use molybdenum (Mo)-based nanozymes (NZs) to augment soybean BNF through two key mechanisms: 1) Stress Protection: Rhizobia are sensitive to environmental stress, especially oxidative stress. Nanozymes are nanomaterials with intrinsic antioxidant enzyme-like activities, potentially safeguarding rhizobia from stress-induced damage and prolonging their function to facilitate BNF. 2) Mo Incorporation: Molybdenum is a crucial element in plant enzymes, including nitrogenase, which catalyzes the BNF process. Mo-based nanozymes may release Mo, which could be assimilated into these enzymes through biotransformation, potentially enhancing their activity. The project will involve engineering Mo-based nanozymes to optimize their effectiveness while unraveling the chemical and biological mechanisms underlying plant responses to these nanostructures.

UKRI Gateway to Research · FY 2025 · 2025-05

The Nonlinear Schrödinger Equation (NLS) is a fundamental model in the study of wave phenomena, particularly in the context of oscillating wave packets. It captures the intricate nonlinear interactions of wave propagation, which often pose challenges for analysis due to their singular nature. In such scenarios, traditional analytical methods often prove inadequate, thus demanding alternative approaches. One such approach is the statistical method employing Gibbs measures, which provides a robust framework to understand the long-term behaviour of solutions to nonlinear PDEs, particularly those demonstrating chaotic or turbulent phenomena. Zakharov's famous question (1983) is a significant example in this regard, seeking to explain the "returning" property of NLS solutions after a rather chaotic evolution. Bourgain's groundbreaking work in the 1990s and recent breakthroughs by Deng-Nahmod-Yue have provided a deep understanding of the Gibbs dynamics of NLS on the flat torus. Nevertheless, challenging open questions remain regarding the Gibbs dynamics of NLS in various geometric contexts. The main difficulty stems from the irregularity of the random initial data, due to the roughness of the support of the Gibbs measure. Over the last three decades, there has been remarkable progress in this field, particularly in the flat torus setting, where the late Fields medalist Bourgain played a leading role. In the past five years, the principal investigator (PI) and his collaborators have made substantial contributions to advancing our theoretical understanding of Gibbs measures and Gibbs dynamics of NLS. See the "Applicant and team capability to deliver" section for further details. This proposal aims to tackle two well-known unresolved issues left open by Zakharov in 1983, Tzvetkov in 2006, and Bourgain and Bulue in 2014. The latter work constructed almost sure global dynamics and confirmed the invariance of the Gibbs measure of NLS posed on certain geometric settings (disc and ball) but did not successfully demonstrate the flow property of the resulting dynamics, which is essential for addressing Zakharov's question. The main aim of this proposal is to tackle these outstanding open problems by introducing a novel approach that leverages random averaging operator theory and random tensor theory. The Nonlinear Schrödinger Equations are essential in understanding various phenomena across scientific disciplines. They are crucial for understanding light propagation in nonlinear optical fibres, the dynamics of Bose-Einstein condensates in quantum field theory, and the modelling of wave packets in various applied sciences. This proposal holds significant value in these fields as it provides a theoretical foundation for advancements in simulations and experimental setups.

UKRI Gateway to Research · FY 2025 · 2025-04

Proteins are a class of hugely important biomolecules. They perform all the functions necessary for life, as well as finding applications as therapeutics. To fully understand the roles of proteins in health and disease, it is necessary to understand their structure and interactions on the molecular level and, most importantly, to gain that understanding in the actual biological context, i.e., in tissue. To address that challenge, we have developed native ambient mass spectrometry (NAMS). NAMS allows the identification and spatial mapping of proteins in tissue, in addition to providing information on structure and interactions with other molecules, including proteins, drugs, small molecule ligands and metal ions. NAMS offers advantages over other spatial biology methods, such as immunohistochemistry, as there is no requirement for labelling and, consequently, no requirement for prior knowledge of a protein's identity. All proteins have a mass, therefore, in principle, all proteins can be detected by mass spectrometry. The potential of NAMS for applications in molecular pathology and drug discovery is truly exciting; however, to date, NAMS has been limited to the characterisation of proteins with higher abundance. Our recent work has focused on the development of the sampling technique nanospray desorption electrospray ionisation (nano-DESI), which offers higher spatial resolution than previous NAMS techniques for direct analysis of proteins from tissue. There is a pressing need to improve both the sensitivity and robustness of NAMS, beyond that achieved with nano-DESI, and to complement these with improved confidence in protein identifications. The aim of this proposal is to realise these required improvements through scientific instrument development, specifically by the integration of lasers with the existing mass spectrometry platform. The first development focuses on the protein sampling device. A new NAMS probe that couples laser desorption, via a pulsed infrared laser, with liquid microdroplet capture of biological material and subsequent ionisation, will be designed, constructed, and validated. The new probe will address the challenge of robustness and advance NAMS towards cellular resolution protein imaging. The second development will integrate a CO2 infrared laser with the mass spectrometer which will improve sensitivity and augment the system with new techniques for protein identification. Together, these modifications will comprise the step-change required to deliver next-generation NAMS and realise its potential to transform life science research.

UKRI Gateway to Research · FY 2025 · 2025-04

Inside our cells, DNA resides in two places - the nucleus and the mitochondrion. The nuclear DNA encodes the organism's blueprint, while mitochondrial DNA (mtDNA) mainly encodes proteins required for energy production. Unlike nuclear DNA, which is derived half from each parent when an egg is fertilised by a sperm, mtDNA is inherited solely from the mother, through the egg. In various species including humans, a fascinating phenomenon occurs during sperm development, where paternal mtDNA is eliminated to ensure only maternal mtDNA is passed on. However, how and why maternal inheritance of mtDNA occurs so consistently across the animal kingdom remains largely unexplored. Through our previous research involving fruit flies, a model organism carrying mtDNA like that of humans, we identified proteins involved in eliminating paternal mtDNA during sperm development. Moreover, we isolated mutant flies capable of transmitting paternal mtDNA to progeny. This project will build on these findings to uncover how and why mtDNA is inherited from only one parent. There are two parts to the project. The first part employs genetic and biochemical approaches to characterise the various proteins identified in our earlier work to reveal how they regulate paternal mtDNA removal during sperm development. This part will help us build a full picture of the mechanisms governing maternal inheritance. The second part involves laboratory evolution experiments using our mutant flies that allow transmission of paternal mtDNA. This part will uncover how violating uniparental inheritance of mtDNA impacts the fitness of individual organisms and overall populations. Our work has broad potential applications in the fields of biology, evolution, and biomedical research. At its core, delving into the mechanisms governing the uniparental inheritance of mtDNA provides molecular insights into this fundamental biological principle that operates across many species. This project extends beyond just understanding how mtDNA is passed down; it investigates what happens if offspring inherit mtDNA from both parents. There are two popular theories about why mtDNA is only inherited from mothers: 1) it limits harmful/selfish mtDNA to certain female groups, thus preventing it from catastrophic spreading at the species level; and 2) it prevents organisms from containing more than one mtDNA genotype as that could cause health problems. Using our special mutant flies that allow paternal mtDNA transmission, we can finally test these ideas in the lab and explore the importance of mtDNA uniparental inheritance for the evolution of life. Our work could also lead to biomedical applications. Compared to mitochondria replacement therapy (i.e. three-parent babies technique), which requires healthy female donors and complicated in vitro fertilisation procedures, paternal leakage could offer a more straightforward and natural way to pass on functional mtDNA to offspring when the mothers carry harmful mtDNA mutations. In addition, our research contributes to the understanding of sperm development, which could help to address issues related to male fertility that affect ~7% of the human male population. In conclusion, this curiosity-driven project will deliver new knowledge about a key biological principle fundamental to all eukaryotic life from molecular to populational levels. It strongly aligns with BBSRC's commitment to advancing the fundamental understanding of living systems and an integrated understanding of health, and driving impactful innovations in bioscience research.

UKRI Gateway to Research · FY 2025 · 2025-04

This project will open a window onto the development of multisensory processing in brain and behaviour in human infancy. It will also galvanise these fundamental discoveries to inform translation by showing how preterm birth shapes the development of multisensory processing, and how multisensory processing differences in infancy affect mental health outcomes. While we know that even the youngest babies are sensitive to aspects of their multisensory environments,1–4 research shows us very little about how infants process and perceive the multisensory world. For instance, although evidence indicates that young infants notice when sights, sounds and touches occur in the same or different places,5–7 we remain largely ignorant about when and how infants come to bind stimuli in these sense modalities into integrated multisensory objects or events.8–10 We also know little about the development of an ability to perceptually segregate sensations which originate from separate places or events. Put another way, it is unclear when and how infants come to sense a world of objects rather than a collection of correlated sensations. This project will build on recent methodological advances by the applicants11 including exciting new pilot data, to shed much needed light onto the developmental origins of multisensory integration and segregation (“multisensory processing”). The applicants will deploy an innovative combination of lab-based and online experimental methods in cross-sectional and longitudinal designs to trace the development of multisensory processing in infancy. They will also build a framework within which fundamental discoveries about infant multisensory development are translated to inform understanding of early differences in multisensory processing and their role in mental health outcomes, specifically in children born preterm. One in 13 births in the UK are preterm (born <37 weeks’ gestation), and individuals born preterm are more likely to be diagnosed with a neurodevelopmental condition and experience poorer educational and mental health outcomes.12–14 Preterm infants have very different sensory and multisensory experiences due to their early exposure to the extrauterine sensory environment, and they show resulting differences in brain structure and function.15 This project will uncover the nature of differences in multisensory processing between term-born and preterm infants. It will also investigate longitudinal relationships between multisensory processing in the first year and mental health at 2 years of age across both preterm and term-born groups. This objective is particularly timely given rapidly growing evidence that sensory and multisensory processing differences play a role in mental health outcomes across neurotypical and neurodivergent individuals.12,16–19 The project team is a uniquely qualified interdisciplinary group of scientists with expertise in multisensory development and neurodiversity (Andrew Bremner and Andrew Surtees, Birmingham BabyLab, Centre for Developmental Science, University of Birmingham), multisensory psychophysics and neurodiversity (Monica Gori, Unit for Visually Impaired People, Italian Institute of Technology, Genova), and perinatal developmental neuroscience and preterm birth (Tomoki Arichi, Centre for the Developing Brain, Department of Perinatal Imaging and Health, Kings College London, and Lorenzo Fabrizi, University College London). The project will also benefit from expert input from Gemma Holder (consultant neonatologist, Birmingham Women’s Hospital), and a steering group of experts-by-experience (parents of infants, individuals born preterm, and parents of infants born preterm). Furthermore, by recruiting and supporting talented predoctoral and postdoctoral researchers, it will create the platform for further research capacity at this crucial frontier of discovery and translational science.