University of Glasgow

UKRI Gateway to Research · FY 2025 · 2025-04

The rapid global rise in antimicrobial resistance (AMR) is a critical public health crisis. It is widely acknowledged to be a One Health challenge, with aquatic environments playing a role of in the development and spread of AMR to people and animals. Aquaculture is an essential food production sector in South-East Asia; however, overuse of antibiotics and poor adherence to antibiotic treatment regimes are considered key contributors to rapid AMR development in the aquatic environment. This includes several classes of antimicrobials essential to treat human infections that are delivered to fish through medicated feed directly in shared waterbodies. Despite these concerns, the risks associated with environmental AMR – including the relative contribution of aquaculture – are poorly characterised and quantified, making it challenging to devise appropriate mitigation strategies or assess their effectiveness. This study will apply a One Health approach to elucidate the contribution of aquaculture production to environmental AMR and the subsequent risks for people, using the Pao River watershed in north-eastern Thailand. In this region, tilapia farming in open cages is commonly practiced and our team has documented high levels of unregulated antimicrobial use, wherein farmers frequently use products with unknown formulations or products not necessarily developed for use with fish. The risks that this poses for driving the selection for AMR are unknown. Moreover, antibiotic-treated feed is commonly prepared without the use of appropriate personal protective equipment such as masks and gloves, representing a potential risk for heightened AMR in fish farmers. Also in this watershed, our previous study revealed high levels of multi-drug resistant E. coli in banteng – a species of wild cattle – compared with local domestic cattle. This has led us to hypothesise that wildlife and people are at risk of acquiring AMR through this shared water source as a consequence of antibiotic use in aquaculture. To characterise and quantify these risks, we will: Assess the relative contribution of different sources of AMR to the Pao River watershed, and determine the degree of sharing of AMR bacteria/genes across the One Health spectrum. This will be done by i) measuring concentrations of antimicrobial residues and types/levels of resistant bacteria up- and down-stream of fish farms and compared with control sites without aquaculture; and ii) determining the AMR profiles of two key indicator bacterial species isolated across the One Health spectrum within the watershed (i.e. from samples collected from people, livestock, wildlife, fish) to assess for the specific contribution of aquaculture amongst other potential sources of AMR. This will be investigated through a combination of phylogenomic approaches and source attribution modelling. Characterise the practices and risks related to antimicrobial use in aquaculture as a potential driver for AMR in the aquatic environment. This will include measuring the quality and quantity of antimicrobials used, how they are administered, and what is driving these treatment decisions. We will assess likely uptake of different intervention options for improving antimicrobial stewardship through a stated-preference choice experiment. Based on the key risks identified, potential interventions to reduce the development and spread of AMR will be co-developed with multiple stakeholders, incorporating regulatory, political, economic and social dimensions. Overall, this study will generate new knowledge on AMR risks from aquatic food production and lead to an intervention pathway.

UKRI Gateway to Research · FY 2025 · 2025-04

Re-configurability of radio frequency (RF) and millimeter-wave (mmWave) systems is expected to become the bedrock of 6G wireless communications. Enabling technologies that can support reconfigurability are still emerging. The project aims to develop active intelligent reflecting surfaces (IRSs) with integrated amplifying capability for 6G wireless communication. IRSs have the capability to redirect incoming signals towards specific, desirable paths, mitigating blockages and interference in complex wireless environments. However, bulk materials enabling such reconfigurability are technologically immature, with traditional materials experiencing high levels of insertion losses and low tuning range, particularly at mmWave frequencies and beyond. In this project, the research team aims to develop an IRS technology with no or very low loss and latency. This will be achieved by combining the attractive features of resonant tunnelling diodes (RTDs), such as their low power operation and ability to operate as reflection signal amplifiers, with transition metal oxides (TMOs), capable of acting as DC-controllable ultra-fast switches and phase shifters to yield a meta-atom. The meta-atom formed in this way will have the capability to both alter the phase and amplitude of the incident signal and compensate for the incident signal loss incurred through traversing the IRS through the amplification by the RTDs. The project has four main objectives. The first objective (O1) is to develop TMO-based switches for the control of amplitude of the signals incident on the IRS. The team will develop TMO-based switches using either VO2 or TiO2 for material design, growth realization, and characterization of binary and mixed/doped metal oxides. They will employ both thermal and plasma-assisted atomic layer deposition to engineer materials with controlled stoichiometry and defect levels. The second objective (O2) is to develop TMO-based phase shifters for the control of the phase of the incident signal on the IRS. The team will investigate the idea for phase shifting of a propagating wave interlaced with sub-skin depth metal TMO/insulator structures. They will examine the fundamental limits of the 'single-bit' insulator/TMO/insulator stack and its performance as a function of the TMO type, their switching mechanism, thickness, characteristics of the dielectrics, biasing lines, and the frequency of operation. The third objective (O3) is to develop RTD reflection amplifiers to compensate for the losses in the circuitry of the IRS and offset the high path loss at terahertz (THz). The team will use RTD's negative differential resistance to amplify the input signal before it is reflected back. Microwave RTD low noise reflection amplifiers have already been demonstrated featuring very low power with 10 dB gain at 5.7 GHz. The feasibility of such amplifiers at K and Ka band frequencies with 100 µW level DC power consumption and a high gain of 32 dB has also been recently demonstrated. The project's ultimate goal (O4) is to combine the results of objectives 1, 2, and 3 to create an IRS capable of controlling the amplitude and phase of incident signals with no or very low loss and low latency. The project's outcomes will be significant in the development of 6G wireless communication technology. The research team will generate new knowledge of the underlying processes and physics for engineering TMOs and their integration with RF and mmWave/THz systems. The project will enable new opportunities for the introduction of IRSs in communication systems for 6G and beyond.

UKRI Gateway to Research · FY 2025 · 2025-03

Gels are incredibly versatile materials, found in common everyday items from food to personal care products, as well as in sophisticated applications such as drug delivery and battery technology. There are many ways of making gels, yet current techniques typically lack precision, providing a limited level of control over a narrow range of achievable properties. There is no easy or obvious approach to control the self-assembly process given that it extends across vast temporal and spatial scales. Our ambition is to explore the science underpinning an entirely new approach to trigger and control gelation using non-equilibrium plasma. Our vision is to exploit the underpinning science to establish a plasma-based technique for gel synthesis, providing an unprecedented level of control over the gelation process, spatially and temporally. This technique will facilitate a transformative step, enabling the rapid exploration of the parametric space of a wide range of gels with minimal cost and effort. The project is split into the following specific objectives: 1. Development of a highly versatile plasma source capable of activating solutions over a wide range of operation conditions. 2. Experimental characterisation of the plasma source as well as the synthesised gels. 3. Understanding the plasma induced-gelation mechanisms utilising experimental characterisation data and advanced numerical modelling. 4. Use this understanding of the plasma-based synthesis process to prepare unusual gels including patterned, localised and shaped gels. Ultimately, our approach will enable the on-demand synthesis of bespoke gels with tailored properties. Our methods will impact numerous industries based on soft matter as well as significant impact in academia where a group of soft matter or complex fluids exists in almost every university in the UK.

UKRI Gateway to Research · FY 2025 · 2025-03

Quantum science has already delivered MRI scanners, GPS positioning, solar cells, and broadly speaking the multi-billion-dollar semiconductor industry across the 20th century. These focused on initial ideas from the quantum physics of electronic properties of matter; however, phenomena under the so-called quantum ‘weirdness’ were unexploited until more recently. These are now expected to deliver unprecedented impact to society with application in quantum cryptography, communication and sensing. The ‘weirdness’ of concern in this proposal is in how properties of one particle can be linked instantaneously with those of another particle regardless of how far separated in distance they may be. This is called entanglement, and the primary objective of this project is to develop practical methodologies for creating and manipulating fundamental excitations of magnetic particles that can be readily incorporated into devices for high frequency microwave operations. More specifically, we will focus on magnon quasiparticles—the quantum of collective oscillations of spins in magnetically ordered materials. The project will focus on exploring the dynamics of many-body magnonic systems, with a particular emphasis on establishing control protocols for coupled magnon dynamics over both short and long distances. By advancing the understanding and control of these hybrid magnonic systems, the research will lay critical groundwork for the next generation of quantum devices and technologies; more specifically, quantum information processing and distribution. This project is scientifically ambitious and aligned strategically with national priorities. It supports both the UK and Canadian national quantum strategies, which recognise the importance of quantum technologies for ensuring security and driving economic growth. By fostering collaborative research in hybrid spin systems, this project will help maintain leadership in quantum innovation and contribute to the development of new quantum technologies with broad and lasting societal impacts.

UKRI Gateway to Research · FY 2025 · 2025-03

Human ill health and disease may be caused or affected by each person's genes. Such diseases are complex and understanding these effects and developing treatments in humans can be difficult. Animal research can help but is only undertaken where there are no alternatives (such as using cells or tissues). Where this is the case, mice can be used to closely model human diseases by specifically changing their genes and how those genes work to mimic changes in patients. As well as understanding diseases, new ways to detect and treat diseases can be tested before use in humans. The National Mouse Genetics Network will use these approaches to understand a number of important human diseases. The Data Platform will allow NMGN knowledge and data to be shared to ultimately find new ways to improve human health and wellbeing.

UKRI Gateway to Research · FY 2025 · 2025-03

Food security is defined when all people, at all times, have physical and economic access to sufficient safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life. As plant biologists, we need to aim for increased productivity and improved nutritional quality of crops to realize food security objectives. In addition, nowadays we have to address the food security issue with the challenge of climate change, which means that we need crops that are more resilient to abiotic and biotic stresses. Sunlight provides the energy source for plants. UV-B radiation, as an intrinsic component of sunlight, additionally works as a key stimulus to regulate numerous aspects of plant growth and development through the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8). UVR8 is the only identified photoreceptor that specifically perceives UV-B and has been proven to regulate multiple responses including metabolism, morphogenesis, defence, photosynthetic competence, thermomorphogenesis, flowering time, etc, many of which are relevant to crop productivity and nutritional quality. My recent work with Arabidopsis has shown that UVR8 is phosphorylated and a highly conserved amino acid in the C-terminal region, Serine 402 (S402) is the main site. I showed that S402 phosphorylation differentially affects protein interactions with UVR8 and enhances the accumulation of hydroxycinnamic acids and flavonoids. This is a groundbreaking discovery in the field that reveals the role of UVR8 phosphorylation in regulation of flavonoid biosynthesis, which is important to both abiotic and biotic stress tolerance and the nutritional quality of harvested products. Discoveries in model plants such as Arabidopsis can provide important directions for crop improvement. UVR8 is a highly conserved protein in the plant kingdom. However, there is little information on how UV-B could regulate crop growth and development through UVR8 and how UVR8 could be manipulated in crops to improve crop productivity, nutritional quality and resilience to climate change. In this Fellowship I will choose Brassica oleracea as the model crop, which is in the same taxonomic family as Arabidopsis. B. oleracea is a widely cultivated vegetable species integral to human diets. It also a genetic pre-cursor of B. napus, which is the major global crop oilseed rape. The discoveries in B. oleracea could be a good indicator for many vegetable and oilseed species. My aim in the project is to apply fundamental discoveries about UVR8 in Arabidopsis to Brassica crops. My specific objectives are to (i) Identify the beneficial traits of B. oleracea regulated by UV-B; (ii) characterize UVR8 function in B. oleracea; (iii) modify B. oleracea UVR8 to improve beneficial traits. To achieve the objectives, I will firstly characterize UVR8 in B. oleracea and investigate UV-B regulated phenotypes under various conditions. I will then use the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas gene-editing technology to knock out UVR8 in B. oleracea, which will enable me to investigate the role of UVR8 in valuable traits. Finally, I will modify B. oleracea UVR8 based on my recent research in Arabidopsis, in particular to increase the content of phenolic compounds. This project will provide the first information on how UVR8 photoreceptor research could enhance the quality of crops, which will give new opportunities for Brassica crop improvement. The discoveries from this project could eventually contribute to realizing the objectives of global food security.

UKRI Gateway to Research · FY 2025 · 2025-03

Misinformation is shaping beliefs and behaviours in health, politics, society, and finances. Statistics show that misinformation is believed 75% of the time, yet only 4% of people have the skills to consistently identify it. The World Economic Forum predicts that misinformation will soon become the number one global risk. Project Real addresses this urgent issue by equipping people with tools and confidence to recognize misinformation across diverse domains. Vision We aim to empower people to identify and respond to misinformation, enabling them to make better choices and help reduce its spread. By helping individuals clean up our online environment and respond effectively to false information, we aim to create a ripple effect of positive change. Through co-creation with stakeholders, we design practical interventions that make a real-world difference. These resources enhance critical thinking and information literacy while fostering a more informed, resilient society where harmful misinformation no longer thrives. Objectives Develop and deliver tailored interventions to schools, charities, and businesses to combat misinformation. Co-create engaging, research-informed resources with stakeholders to ensure relevance and impact. Address misinformation challenges across diverse sectors, including education, law enforcement, and business. Areas of Focus Education: Teachers often create lessons on misinformation but may lack research-based or co-created materials. We collaborate with educators and students to create effective, relatable resources. Charities: Many organizations rely on outdated or ineffective interventions. Partnering with charities, we create tools aligned with their missions, enhancing their impact. Businesses: Most companies focus on cybersecurity but overlook modern threats like deepfakes and generative AI. Project Real offers engaging, up-to-date solutions tailored to their needs. Why It’s Important Misinformation undermines trust, fuels extremism, and influences behaviours in harmful ways. Online, we are particularly vulnerable to cognitive shortcuts that make us more likely to believe false information. Project Real encourages systematic thinking, helping people evaluate content critically and avoid being misled. The impacts of misinformation are widespread: In schools, it shapes young people’s understanding of the world. In workplaces, it affects decision-making and trust. In charities, it undermines efforts to tackle societal issues. By addressing these challenges at their root, Project Real contributes to a more informed and resilient society. Why It Will Succeed Proven Demand: Our website has attracted over 47,000 organic visits, highlighting the need for resources. Teachers have shown strong interest in targeted, age-appropriate content. Established Partnerships: Collaborations with Education Scotland, Police Scotland, and The Melissa Institute enable us to create highly relevant, impactful materials. Research-Driven Approach: Co-creation ensures that our interventions are grounded in both academic research and real-world needs. Studies show that co-created resources are more effective and engaging. Tailored Solutions: Unlike generic safety courses, our interventions are customized to each organization’s unique challenges, increasing their effectiveness. The Path Forward Project Real leverages its strong foundation in research and collaboration to tackle one of today’s most pressing issues. While individuals often overestimate their ability to spot misinformation, organizations recognize its risks. By working directly with schools, charities, and businesses, we create interventions that make a tangible difference, helping society become more resilient to the harmful effects of misinformation.

UKRI Gateway to Research · FY 2025 · 2025-03

Antimicrobial resistance (AMR) represents a significant global health challenge, threatening the effectiveness of existing antibiotics and complicating the treatment of infectious diseases. The increasing rate of emergence of multidrug-resistant (MDR) pathogens has created a pressing need for innovative approaches to combat AMR. Pseudomonas aeruginosa stands out as a prominent AMR pathogen, posing significant challenges in clinical settings. Known for its adaptability and intrinsic resistance mechanisms, this opportunistic pathogen thrives in diverse environments, including hospitals. MDR P. aeruginosa represents one of the main causes of ventilator-associated pneumonia (VAP), a condition that affects 5-40% of intensive care units (ICU) patients that undergo mechanical ventilation for more than 48 hrs. P. aeruginosa ability to form biofilms in endotracheal tubes that are difficult to eradicate favours its seeding into the patients’ airways and lungs. The remarkable resistance that P. aeruginosa exhibits to diverse antibiotic classes renders its eradication in VAP patients challenging and, in many cases, leads to recurring infections, longer hospitalisation periods, increased economic toll on health services and high mortality rates. Phage therapy is emerging as a promising solution to combat AMR infections. In several trials phage cocktails have demonstrated efficacy in targeting MDR P. aeruginosa strains and eradicating biofilms in VAP patients, thus rendering phage-based therapies a promising alternative route to treat VAP patients. However, the evolutionary arms race between bacteria and phages has yielded a diverse and broad arsenal of phage defence systems within bacterial populations. Recent research has identified approximately 200 unique anti-phage systems, highlighting the intricate dynamics between bacteria and phages during infection. P. aeruginosa harbours an extensive repertoire of anti-phage systems, with certain strains carrying up to 17, conferring resistance against most known Pseudomonas-targeting phages. Additionally, anti-phage systems are often carried on mobile genetic elements (MGE), such as prophages. These represent genomic locations that can be frequently exchanged across bacterial strains of the same species through horizontal gene transfer. Localisation of defence systems on MGEs favours their mobility in mixed populations of Pseudomonas strains at the site of infection, provide population-wide protection against a wide diversity of phages. The prevalence of these defence mechanisms in Pseudomonas and their mobilisation across strains poses a significant obstacle for phage therapy, potentially compromising the efficacy of phage cocktails against heterogeneous populations of P. aeruginosa strains commonly encountered in VAP infections. It is therefore of paramount importance to understand how defence systems, their interaction network, and their mobility across heterogeneous populations can affect the efficacy of phage therapy and its promise in combating AMR infections in VAP patients. With this project, I will address this knowledge gap by utilising an endotracheal tube biofilm model to investigate P. aeruginosa MGE-encoded anti-phage systems' mobility and competition against phage cocktails in a physiologically relevant context. The data and insights obtained in this study will be leveraged to explore routes for engineering and designing phage-based therapies with enhanced efficacy. These therapies will be tailored to each patient and capable of circumventing anti-phage systems, providing an effective and potent tool to combat AMR. Furthermore, this study will provide a high-throughput platform that can be extended to investigate other VAP-relevant pathogens, poly-microbial infections, and the impact of the synergistic interactions of multiple anti-phage systems encoded in specific pathogens on the efficacy of phage cocktails.

UKRI Gateway to Research · FY 2025 · 2025-02

The parasite that causes malaria infects hundreds of millions of people and causes hundreds of thousands of deaths every year, primarily in children under the age of five in Africa. Global malaria control is heavily dependent on antimalarial drugs, but resistance to the current frontline antimalarial, artemisinin, has emerged globally, threatening current control efforts. New drugs and new drug targets are urgently needed. Almost all complex cells, including the cells in our body and the single-celled parasites that cause malaria, require an energy-converting compartment called the mitochondrion to survive. Inside this mitochondrion there is a chain of protein complexes or "micro-machines" that drive the conversion of energy. These micro-machines are essential for the malaria parasite's ability to grow inside human red blood cells, which causes the symptoms of malaria, and for their ability to spread from person to person via mosquitoes. Due to these critical roles, inhibitors that disrupt the activity of these parasite micro-machines, without affecting their human counterparts, can make effective anti-parasitic drugs. There is already one antimalarial drug, atovaquone, along with a series of inhibitors in different stages of drug development, which target complex III (CIII), the third micro-machine in the chain, but we currently do not know the exact details of how this complex works. Likewise, we cannot explain why these inhibitors interacts so well with parasite CIII, and not the human counterpart. The answers to both questions, which our project aims to provide, will likely help make better drugs. Human CIII is made of eleven parts, eight of which supports its stability and its interactions with the other micro-machines in the chain. We and others found that parasite CIII is lacking some of these eight parts, and instead contains parts not found in the human complex. These differences in malaria and human CIII composition are intriguing as they represent divergence in a fundamental cell biology process and a unique feature of this deadly infectious organism which could potentially be targeted by new drugs. It is not currently known how this divergent composition affects CIII structure and function. This project will reveal how these unique parts of parasite CIII function in parasite growth and survival, and further examine their importance for the interaction between micro-machines in the chain, and their role in parasite development into their transmissible form. While atovaquone is highly potent, the malaria parasite can become resistant to it rapidly, so other inhibitors that target the parasite CIII and are active against atovaquone resistant parasites need to be developed. CIII has two pockets where drugs could bind: atovaquone binds one pocket, while some of the newly developed inhibitors bind to the other. We will use advanced structural approaches to precisely map the binding interaction of at least two inhibitors, which each bind a different pocket. This will provide critical information to support the future development of new antimalarial drugs. In summary, this project will uncover the composition, function, and mechanism of the malaria CIII focusing on the features that are divergent from the human complex. It will therefore expand our understanding of a fundamental cell biology process in divergent organisms, while also providing detailed insight into how drugs are able to inhibit malaria CIII and informing antimalarial drug development.

UKRI Gateway to Research · FY 2025 · 2025-02

POLART will examine the relationship between art and policy through a double focus: an investigation of how art may produce policy knowledge 'that might be otherwise' (Law 2017) and how, conversely, policy issues have altered the contemporary artistic canon and forms of engagement. Our point of de-parture is that research has so far focused almost exclusively on the role of science and measurement in the production of policy, at the expense of an examination of how art can problematize the status-quo, question well-trodden paths, and offer alternative and imaginative ways of dealing with social problems. Although the relationship between art and policy-making is vastly under-explored, the arts have always been an essential element of how policy makers make sense of, interpret and hence gov-ern societies. POLART's daring promise is to develop interdisciplinary analysis that for the first time investigates the dynamic interrelationship of art and policy systematically. Through innovative methods, and at the crossroads of public policy, science and technology studies and the sociology of art, POLART will set the intellectual foundations of the novel 'Art and Public Policy' field. A major task of the study -and the field - will be the decoding of the material and performative 'hybrid knowing spaces' (Law 2017), as they emerge at the intersections of the art and the policy worlds. How do these aims translate in empirical terms? POLART will initially examine major international art exhibitions, in order to explore the relationship between art and policy problematization post-1989. Second, we will examine how, why and with what effects, the arts can mobilise policy change both at the global and local levels. Finally, we will explore how the arts may shape national/local policy mak-ers' political values towards the production of equitable and participatory governance, fit for the chal-lenges of the 21st century.

UKRI Gateway to Research · FY 2025 · 2025-02

Context and Challenge This project focuses on developing and analyzing advanced materials for superconducting and quantum technologies, specifically targeting the improvement of superconducting qubits, which are essential for quantum computing. Traditional materials used in qubits, like aluminum, face limitations such as high dielectric loss and poor uniformity, which negatively impact qubit performance and scalability. To address these issues, we propose using niobium nitride (NbN), which offers higher critical temperature and reduced oxidation, potentially enhancing qubit stability and performance. These advancements are crucial as quantum computing revolutionises various fields including drug discovery, energy management, artificial intelligence, and autonomous systems. Aims and Objectives Advanced Material Fabrication    Utilize state-of-the-art atomic layer deposition (ALD) to grow high-uniformity NbN layers.    Develop high-quality NbN/AlN/NbN Josephson Junctions (JJs) with precise control over the tunnel barriers. Comprehensive Characterization    Conduct thorough material characterization using advanced tools such as electron microscopy and atomic force microscopy (AFM) at both room temperature and cryogenic conditions.    Investigate the material properties of these films, focusing on their stoichiometry, critical temperature, and kinetic inductance. 3D Integration  Develop high-aspect ratio through-silicon vias (TSVs) coated with nitride films to enable 3D superconducting interconnects, facilitating large-scale quantum processor integration.   Fabricate and connect superconducting qubits, interposer chips, and routing chips to create integrated 3D quantum circuits. Performance Optimization Benchmark ALD-grown NbN films and JJs against conventional qubit technologies. Optimize fabrication processes to minimize defects and enhance qubit coherence times. Potential Applications and Benefits The successful development of these advanced superconducting materials and structures will have significant implications for quantum technology. By improving the performance and scalability of superconducting qubits, this project will contribute to the advancement of quantum computing. Quantum computing has the potential to revolutionize fields such as drug discovery, where it can drastically reduce the time required to develop new medications, and energy management, where it can optimize the distribution and usage of energy resources for better sustainability. Moreover, the project's outcomes will benefit industrial partners like Oxford Instruments Plasma Technology (OIPT) and Kelvin Nanotechnology (KNT), enhancing their technologies and opening new market opportunities through innovations in areas such as sensing, communications, and fundamental research. Broader Impact This project aligns with national and global priorities in quantum technology development, supporting the UK's strategic vision to become a leading science and technology superpower. The work will be disseminated widely through high-impact journal publications, conferences, and public engagement, ensuring broad visibility and impact. Presentations at international conferences, such as the APS March Meeting and IEEE Quantum, will further enhance the project's visibility within the scientific community. This project promises robust and reliable outcomes through collaboration with leading institutions and leveraging existing infrastructure, such as the James Watt Nanofabrication Centre at the University of Glasgow and the advanced facilities at the University of Tokyo. The integration of industrial-grade processes and advanced material research positions this project to pioneer significant advancements in the field of quantum computing, driving both scientific and economic benefits. Ultimately, the project reduces barriers to entry for developing superconducting technologies, paving the way for the commercialization of high-quality quantum devices and supporting the growth of the quantum technology industry. By addressing fundamental issues with superconducting qubits and improving their stability and lifespan, this project aims to make quantum computing more viable and scalable for industrial applications, with a profound impact on the future of technology and society.

UKRI Gateway to Research · FY 2025 · 2025-02

Imagine crafting powerful materials for next-generation electronics and clean energy technologies, all while minimising environmental impact. This research project proposes a groundbreaking method to achieve this by harnessing the power of light instead of polluting chemicals. Traditionally, creating materials with a specific "handedness" called chirality is crucial for various applications, including medicine and efficient electronics. However, current methods to manufacture these chiral materials rely on harsh chemicals and significantly contribute to CO2 emissions. This project tackles this challenge head-on by proposing a novel light-driven approach that aligns perfectly with the growing trend towards sustainable manufacturing practices. It directly addresses UN Sustainable Development Goals (SDGs) for clean energy (SDG 7), responsible consumption and production (SDG 12), and climate action (SDG 13). The core concept involves directly inducing chirality within flexible two-dimensional (2D) materials like graphene and perovskites using light. These materials hold immense potential for future technologies, but traditional chemical manufacturing methods often limit their ability to achieve chirality. The proposed method leverages the transfer of angular momenta from light beams to impart a sense of twist to the highly flexible 2D materials This eliminates the need for energy-intensive chemical processes and opens the door for a wider range of materials to be rendered chiral. Furthermore, by harnessing green electricity to power light energy efficient light sources, this approach significantly reduces the environmental footprint associated with material production. To further enhance the efficiency of light-induced chirality induction, the project explores the strategic utilisation of nanostructures. These microscopic structures act like light cavities, concentrating the incident light and amplifying the optical forces within sub-wavelength dimensions. This focused light interacts with the 2D materials, exerting a torque that can manipulate the atomic arrangement and induce chirality. This approach is particularly promising for highly flexible materials like single-layer graphene and MoS2, as well as soft crystals like hybrid organic-inorganic perovskites, all of which are relevant for next-generation computing and energy technologies. To validate the effectiveness of this light-driven approach and explore potential applications, the project will delve into the characterisation of the manufactured chiral materials. Specifically, the research team will focus on measuring the spin transport properties of the materials. Spintronics, a rapidly developing field, utilises electron spin for information processing, potentially leading to faster and more energy-efficient electronics compared to traditional methods. By analysing the spin transport properties, the project aims to assess the functionality of the light-induced chirality and its potential for spintronic applications. This project fosters a collaborative effort between leading research teams in the UK and Japan. The UK team brings extensive expertise in unravelling the complexities of chiral light-matter interactions, while the Japanese team offers complementary strengths in solid-state chirality, particularly concerning chiral-induced spin transport. This synergy between expertise in light manipulation and solid-state materials is crucial for the success of this multidisciplinary project. By successfully implementing this novel light-driven approach, the project has the potential to revolutionise the field of material science. The ability to produce functional chiral materials sustainably opens doors for the development of next-generation technologies with improved performance and reduced environmental impact. Imagine electronics with enhanced efficiency and lower energy consumption or cleaner methods for producing green hydrogen fuel. This research directly contributes to achieving the UN's SDGs for a cleaner and more sustainable future, making significant strides towards a greener tomorrow.

UKRI Gateway to Research · FY 2025 · 2025-02

Organic semiconductors are important materials that find wide usage in organic light emitting diodes (OLEDs), solar cells and next generation optoelectronic devices. Their performance is governed by how excited electronic states form, evolve, interact and decay, with numerous loss channels frequently limiting their efficiency. It is a pressing question to obtain knowledge of these losses and identify materials or chemical motifs that reduce them. Measuring molecules one at a time, with single molecule spectroscopy (SMS), offers unrivalled access to fundamental knowledge, including observing emergent behaviour not possible with ensemble techniques, which suffer from simply measuring a single “average” of millions of molecules’ properties. However, SMS typically relies on recording the emission of light by molecules, and thus does not directly enable understanding of many important processes in the excited state that involve weak or dark transitions, for example triplets, charge transfer, or polaronic states. Additionally, the spectral evolution of excited state losses in SMS is typically hard to access, as this occurs on picosecond/nanosecond timescales and is not trivially measurable with single pixel single photon detectors. In this project two teams, based in Glasgow and Tokyo, will combine their knowledge and expertise to realise two new techniques to enable unrivalled new information on excited states in organic semiconductors to be obtained, including directly measuring non-emissive states and observing fast (ps/ns) spectral evolution of excited state quenching. This will be achieved by exploiting quantum optical sources and detection schemes to measure single molecule transient absorption and spectrally resolved photon antibunching. The former will give direct observation of important non-emissive excited states, enabling how they form, evolve and decay on the femtosecond to millisecond timescales to be tracked, while the latter will enable measurement of the energetic heterogeneity in excited state losses to be recorded. Two classes of materials will be examined with these techniques, one widely studied polymers used in OLEDs, while the other a progression of high efficiency photovoltaic materials. The outcomes of this project will be to contribute important new fundamental understanding of the behaviour of excited states in organic semiconductors. By measuring single molecules one at a time, unique information on how their chemical structure relates to their optoelectronic properties can be obtained that is otherwise not possible. Here chemical motifs that are responsible for advantageous properties will be identified and design rules for new materials devised.

UKRI Gateway to Research · FY 2025 · 2025-02

As the world transitions to use more intermittent renewable energy sources such as wind and solar in response to global warming, consuming electricity when renewable energy is available becomes beneficial. This applies across sectors, but aligning computing with low-carbon energy generation is particularly critical. The ICT infrastructure needed for computing – including data centres, devices, and networks – consumes massive amounts of energy, already rivalling aviation at 2-3% of global consumption. Around a third of this can be attributed to cloud data centres and more and more workloads are expected to migrate to the cloud in the future. Clouds provide uniquely flexible compute environments, particularly for scalable batch processing applications like data analytics, machine learning, and scientific workflows. The elasticity of these environments and applications allows the shaping of computational loads to closely match the availability of low-carbon energy. That is, applications can be scheduled and scaled dynamically to use most cloud resources when the carbon intensity of energy grids is lowest. Carbon-aware cloud computing has been proposed repeatedly over the last few years, and the emission savings are expected to be substantial. However, the potential has so far not been realised beyond simulations, laboratory experiments, and specific internal cloud provider applications. Much of the work to date ignores the need for fine-grained insights into application performance – such as runtimes and scalability of individual computational steps and overhead for pausing applications while carbon intensity is high. In addition, the basic idea has been criticised for ignoring the risk of further increasing peak cloud loads, with negative economic and environmental consequences. Addressing these challenges, Casper aims to develop the first Stepwise Performance-, Interruption-, Resource-, Carbon-Aware Scheduler (SPIRCS) for large scalable batch data processing applications in elastic compute clusters. For this, we will research how the availability of spare resources in public and private clouds can be optimally anticipated to reduce the footprint of delay-tolerant applications (WP1). We will furthermore develop fine-grained performance models that accurately capture how individual processing steps – e.g. tasks or iterations – of large-scale batch data processing applications can be executed, paused, and resumed to maximise cloud usage when low-carbon energy is available (WP2). Finally, we will implement these results in one novel SPIRCS system for data analytics and workflow applications (WP3) and will evaluate its effectiveness in use cases covering both public and private cloud services (WP4). Our objectives are to develop the SPIRCS methods needed for reducing the emissions of large scalable batch data processing applications in clouds by 10-25% (Objective A), implement SPIRCS for two widely used open-source cluster computing frameworks (Objective B), and evaluate it on top of commercial public cloud services and a research centre’s private cloud (Objective C). In addition, we will strive to raise awareness of cloud application carbon footprints and support overall demand-side management, sharing, for example, how spare cloud capacity aligns with low-carbon energy availability. To ensure that Casper is set up to make pioneering contributions beyond the confines of a university laboratory, we will actively engage with our partners, who represent two different routes to real-world impact: Where AWS and the BBC will bring in the viewpoints and expertise of a major public cloud provider and user, HU Berlin will do so for a private cloud managed and used by a major research organisation.

UKRI Gateway to Research · FY 2025 · 2025-01

Our immune systems recognise and respond to the pathogens that infect us and cause disease. An important element of our immune system is its ability to learn from previous infections and provide better protection should we meet the same pathogen again. We achieve this by forming immune memory cells that act quickly in response to subsequent infections. This ability to remember past infections is the basis for the success of vaccines. Most vaccines work be training immune cells called B cells to make antibodies that stick to the pathogen and stop it infecting us. Some pathogens, including the viruses that cause COVID19 and the flu, can change how they look and stop the antibodies sticking to them. This allows the virus to sneak back into our bodies. Fortunately, we have other immune cells that can remember past infections. These include CD4 T cells, known as the orchestrators of immune responses. CD4 T cells work with many other cells to control and clear pathogens. But we don't know enough about memory CD4 T cells to design vaccines that drive the generation of the most protective cells. We study the CD4 T cells that recognise flu viruses. We ask how memory CD4 T cells are made, how they change over time, and how they protect us against subsequent flu infections. To do this, we made a unique mouse that enables us to easily identify the CD4 T cells that recognise flu. Our first question is based on our finding that the memory CD4 T cells that form following a flu infection are very heterogenous. We want to ask when this heterogeneity develops, whether it is different depending on where the memory CD4 T cells are found in the body, and how it is affected by a subsequent infection. We will examine individual memory CD4 T cells to ask what molecules might control their generation and survival and how the cells maintain their identity. These data will help us understand the rules that affect the lifespan and function of these important cells. One way CD4 T cells control viruses is by communicating with other cells by making proteins called cytokines. Only some memory CD4 T cells can make cytokines. We found that the memory CD4 T cells that can make cytokines are able to stay alive for longer periods of time than those that can't. We will examine this enhanced survival more closely and ask whether these cells can keep making cytokines throughout their lifetime or whether they switch to being a different type of memory cell. For our last question, we will ask which molecules are important in the survival of a particular population of memory CD4 T cells. These are called multifunctional CD4 T cells and they can make several different types of cytokines. They have been linked to protection from various infections in animal models and in humans. We have chosen to examine the role of two molecules, Myc and Foxo1, based on our current studies. Multifunctional CD4 T cells make more of these molecules than other memory cells, suggesting that Myc and Foxo1 are important for how they survive and/or function. We will manipulate these molecules and ask whether and how this affects the memory CD4 T cells that form following flu infection. These experiments may help explain why multifunctional cells are more protective than other memory populations and potentially provide clues on how we could design vaccines to make better memory CD4 T cells. Together, our studies will provide us with a much broader and deeper understanding of memory CD4 T cells. We will reveal new knowledge about how these cells form, survive and function to protect us from infectious disease.

UKRI Gateway to Research · FY 2025 · 2025-01

Stomata are microscopic pores that mediate gas exchange across the impermeable cuticle of plant leaves. Stomata open to allow CO2 entry for photosynthesis, and they close to prevent water loss via transpiration and leaf drying when atmospheric humidity is low. The guard cells that drive stomatal opening and closing generally respond slowly to environmental change - for example, fluctuations in daylight as clouds pass overhead - leading to periods when photosynthesis is limited by CO2 availability and when water is lost without commensurate gains in carbon assimilation. Reducing the impacts of this stomatal hysteresis has proven possible by enhancing guard cell ion transport that facilitates stomatal movements. Stomata also exhibit use-dependent, 'memory-like' latencies in responsiveness with recurrent environmental challenge. A use-dependent latency, or 'carbon memory', slows stomatal kinetics with repeated fluctuations in response to light and CO2, and a related phenomenon, dubbed 'programmed closure', slows stomatal recovery following exposures to the water-stress hormone ABA. As these memory-like phenomena can degrade both longer-term carbon assimilation and the efficiency of water use by the plant, understanding their mechanics and regulation is certain to inform efforts towards greater crop yields. From past research we know that membrane vesicle traffic makes a major contribution to latencies in stomatal responsiveness. Notably, with ABA vesicle traffic removes the KAT1 K+ channel out of the cell membrane and later recycles the channel to the membrane for K+ uptake and stomatal re-opening. This cycling of KAT1 was shown to require the vesicle trafficking protein SYP121. Our studies indicate a similar cycling process with recurrent changes in light and CO2. What we do not know is how these cycling events are initiated and regulated. Recently, we discovered a protein with similarities to a component of the BORC complex that in mammals is thought to regulate vesicle trafficking, neuronal transmission, and insulin secretion. The plant BORC1-like protein, BLP1, is strongly expressed in guard cells; it binds trafficking SNARE SYP121 in an ABA-dependent manner; and it alters K+ channel activity in association with SYP121. Furthermore, mutants of blp1 and of two putative BLP1 partners exhibit cumulative use-dependent changes in stomatal responsiveness to light and CO2 with consequences for carbon assimilation and plant water use. These findings point to hitherto unexpected mechanism that controls vesicle trafficking and stomatal latencies. Most important, our findings point to a trafficking mechanism at the centre of memory-like behaviours affecting how plants respond to environmental change. We intend to resolve the mechanics of vesicle traffic regulation and cycling that underpin the latencies regulating stomatal memory-like behaviours. We want (1) to examine how BLP1 and its putative BORC complex partners regulate SNARE complex assembly and SYP121-associated interactions, (2) to determine the impact on the KAT1 channel as a marker for environmentally sensitive traffic and activity, and (3) to characterise the actions of BLP1 and its partners on stomata, biomass gain, and plant water use efficiencies. The research is for fundamental knowledge directed to uncovering the 'rules of life'. Nonetheless, it holds immediate relevance for crop improvement. As the global demand, especially in agriculture, outstrips fresh water supplies, the knowledge gained from this work will help inform strategies to increase crop performance and efficiencies for mitigating the crisis in water availability and crop production.

UKRI Gateway to Research · FY 2025 · 2025-01

Mesenchymal stromal (or stem) cells (MSCs) are adult stem cells that can be easily isolated from the bone marrow or fat tissue. MSCs can turn into bone, cartilage, ligament, tendon and fat-forming cells and so there is a large interest for their use in tissue regeneration. For example, adding MSCs, as a cell therapy, to broken bones or damaged cartilage. With an ageing population where the health of the skeletal system affects the quality of everyday life, this is important. Also, as we age, we can develop diseases that may require transplant procedures. MSCs are immunomodulatory. This means that they can prevent transplant rejection, being used as a drug rather than for their regenerative potential. It is important to note that as MSCs are immunomodulatory, they can be an allogeneic therapy - i.e. cells can be banked by manufacturers and given to different patients, providing an "off-the-shelf" cellular therapy solution. MSCs are also important in the development of cancers, such as blood cancer. As blood cancers develop, the cancer cells signal to MSCs in the bone marrow and the MSCs alter the environment in favour of looking after the cancerous cells rather than healthy blood cells. We propose that MSCs can be delivered to complement chemotherapy, to regenerate healthy bone marrow and look after normal blood cells provided by bone marrow transplants. MSC-based therapies, therefore, hold massive potential to give us more years of high-quality life.  However, despite the first MSC-based clinical trial being >25 years ago, the therapies are not commonly used. This is due to the current lack of scalability. NICE looks at new therapies and medicines based on quality-adjusted life years (QALY) and typically views £20k per QALY as cost-effective. The price of MSC therapies is currently much higher than this because we cannot manufacture them efficiently. The problem is that as MSCs proliferate (or grow) in the lab, outside of the body, they age and either stop proliferating or they differentiate in an uncontrolled manner. This means we can only grow relatively few from each donor, keeping the price high through an inability to effectively scale up production and maintain MSCs in an undifferentiated state.  The MAINSTREAM EPSRC research and partnership hub for health technologies in Manufacturing Stem Cells for Regenerative Medicine, Immunotherapy and Cancer, will solve this problem and make MSC therapies a reality in the UK and around the world. We have developed materials that tell MSCs to remain as stem cells, to proliferate for longer, to retain their immunomodulatory and regenerative properties and not to age or differentiate in culture. In the hub, we will link these materials and understanding to non-invasive characterisation and manufacturing technologies, so that we can scale-up our materials to an industrial level and study cell phenotype as they grow. To achieve this, it is critical that we link with medical doctors, cell manufacturers and the government. It is paramount that we also link to patients and engaged public to ensure that we focus on user needs and make relevant and usable cell therapies in a responsible manner that regulators and policy-makers are ready for. The hub, and the UK leadership it will provide, will unlock the huge potential of these stem cells to give us not simply more years of life, but years of higher quality life.

UKRI Gateway to Research · FY 2025 · 2025-01

The ability to enhance photosynthetic capacity remains a recognised bottleneck to improving plant productivity. Phototropin receptor kinases (phot1 and phot2) play an important role in this regard by coordinating multiple light-capturing processes that serve to maximise photosynthetic efficiency and promote growth. These include phototropism, chloroplast accumulation movement, leaf flattening and positioning. Leaf architecture is an important agronomic trait that can enhance photosynthetic capacity when plants are grown at high-density However, little effort has been made to target these pathways for improved biomass production as this requires a better molecular understanding of how phot receptor kinases signal from the plasma membrane to establish these distinct responses. Altering the abundance of phot signalling components has already proved successful in improving stomatal performance. Extending this approach to coordinate further enhancements in photosynthesis will require a deeper understanding of how phots optimise light capture through different light capturing processes. The substantial body of preliminary work outlined makes us uniquely placed to dissect and address key gaps in our knowledge regarding the early events associated with phot signalling and open new possibilities to manipulate photosynthetic productivity to meet a rising global demand for plant biomass. This proposal builds on our combined strengths in plant photobiology and our recent findings demonstrating that phots phosphorylate multiple members of the NPH3/RPT2-like (NRL) protein family through a common mechanism, with each NRL differing in their contributions to specific light-capturing processes. Directed proteomic approaches have also uncovered the identity of new interaction targets that are important for NRL signalling and for regulating NRL action/subcellular localisation through dynamic changes in protein phosphorylation. The aim of this project is to elucidate the functional consequences of NRL phosphorylation and better understand how specific NRLs contribute to establishing different light-capturing responses. The outcomes of this work will not only advance our knowledge of the underlying mechanisms involved but will provide new opportunities to alter the abundance of specific regulatory components for yield improvements through increased photosynthetic competence.

UKRI Gateway to Research · FY 2025 · 2025-01

Hybrid silicon detectors have revolutionized the detection and measurement of radiation. The range of applications are vast and include: detectors for fundamental physics (e.g., particle, nuclear, astronomy and solar physics), in our understanding of biology and materials at synchrotron facilities and in electron microscopes, and even radiation monitoring of astronauts on the international space station. The best hybrid pixels detectors count individual photos incident on the sensor. These devices are noiseless due to the use of a discriminator after the first amplification stage. This discriminator results in a lowest possible detectable energy of the incident radiation. The most performant photon counting hybrid detectors have a minimum threshold that corresponds to a minimum detectable X-ray energy of 2keV. The noise contributions at the input of the front-end amplifier are due to detector capacitance, leakage current and inductance. The spatial resolution of the most advanced hybrid pixel detectors (e.g. TimePix and Dectris detectors) are order 16um obtained with 50um pixels. The temporal resolution of the most advance TimePix4 is 200ps, while the next generation proposed for the VELO-II upgrade (PicoPix) will have 20ps timing resolution. To take advantage of the increased electronics time resolution, the sensors need to be improved from standard planar devices. Such detectors are thin low gain avalanche detectors (LGAD) or 3D detectors. To allow lower energy detection the sensor must have a near transparent backside contact to allow transmission of the incoming low energy radiation. The sensor must also have reduced input noise on the front-end amplifier and therefore low capacitance and ideally have internal gain. The LGAD device has a lower capacitance than a 3D detector and due to the internal gain can further reduce the minimum detectable incident radiation as well as produce excellent 20ps timing resolution. The trench LGAD is able to produce uniform gain over a 50um pitch pixel array, unlike a 3D detector with its intrinsic dead space. These characteristics place the LGAD at an advantage over the 3D detector for low energy detection. This project will develop a small pixel thin LGAD device to obtain 20ps timing resolution with an ultra-transparent backside contact for extremely low energy detection bonded to a TimePix4 pixel chip. The goal is to have 20ps timing resolution with a minimum detectable X-ray energy of 250 eV. These are an order of magnitude improvements on the state-of-the-art. The immediate applications of these devices are soft and tender X-ray detection at synchrotrons which are key for imaging of low atomic number elements that are responsible for many biological functions as well as being key to understanding future energy storage materials. In addition to low energy X-ray detection many applications demand radiation hardness. The project will also develop the most radiation hard LGAD devices by making a systematic investigation, first be simulation and then fabrication, into the effects of doping profiles and background dopant types on radiation hardness. Radiation hardness will be tested for both protons and X-rays. The most immediate application of a radiation enhanced LGAD will be in particle and nuclear physics.

UKRI Gateway to Research · FY 2025 · 2025-01

The tumour microenvironment (TME) plays fundamental roles in cancer pathology and response to therapies. The intratumour microbiota has emerged as a non-negligible active component of the TME. The diversity and spatial distribution of the intratumour microbiota are closely associated with prognosis in different cancer types. Moreover, there is mounting evidence that it regulates cancer pathogenesis and efficacy of anticancer therapies via various mechanisms, including immune regulation and metabolic alterations of the host cells. However, mechanisms by which host-microbiota interactions mediate anti-tumour effects via modulating the immune TME are largely unknown. In spite of the potential for intratumor microbiota to be a prognostic indicator, and of their interactions with host cells to unravel new strategies for precision medicine in cancer, research in this field is moving forward at a slow pace. The fundamental challenge is the low biomass of the intratumour microbiota and the integration of multi-modal data. Here we are tackling this challenge by establishing an innovative platform that combines complementary cutting-edge spatial-profiling technologies, Raman spectroscopy and mass spectrometry (imaging and proteomics), with advanced AI-driven image analysis and bioinformatics. Together, these will map the intratumour microbiome, cell type specific metabolic states and the proteome associated with the presence of intratumour microbes in situ in clinical tissue samples. In parallel, we will also develop novel microfluidic platforms that will uniquely enable the enrichment of the microbiome for in-depth genetic investigations. When combined, the data from the Raman, metabolic and proteomic imaging and bioinformatics will enable a massively holistic view of the cancer cell's biology with high spatial resolution and detailed molecular information. As proof of concept, we will apply this platform to tubo-ovarian high grade serous (HGS) tumour tissue samples. HGS ovarian cancer is the most lethal gynaecological malignancy in the developed world with limited therapeutic opportunities for the patients. While immunotherapies have revolutionised anti-cancer treatments due to long-term survival benefits, their effectiveness has been limited in HGS ovarian cancer patients due to the immunosuppressive TME. Finding ways to predict which patients respond to immunotherapies and the development of new treatments to revert immunosuppression could be a game changer for these patients. Of particular interest here is the prospect of investigating mechanisms behind the intratumoral microbiome's close association with the immune TME and prognosis in HGS ovarian cancer. The data generated with our platforms have the potential to identify microbiome biomarkers of immunosuppression. Moreover, Raman spectroscopy offers unprecedented speed to determine the diversity of the microbiome, hence the potential of the technology developed here for rapid patient stratification for treatment regimens and clinical outcomes. Furthermore, our data on host-microbiota interactions can lead to generating hypotheses on mechanistic functions of the microbiota in regulating tumour immunity, ultimately advancing the development of new therapies to boost tumour immunity and response to immunotherapies. More broadly, our platform will impact other cancer types and even other fields beyond cancer because of its applicability to any tissue samples.

UKRI Gateway to Research · FY 2025 · 2025-01

“Generation Malawi”, an ambitious multidisciplinary research programme, is creating a rural and urban, linked prospective family and birth cohort study of mental health and neurodevelopment, nutrition and cardiometabolic development in a very low-income African nation. This enables the investigation of parental mental and physical health, infant neurodevelopment (and other long-term conditions) and genomics in rural and urban Malawi, giving representation to some of the world’s most marginalised people. Importantly the diverse investigator team is building research capacity in Malawi to capitalise on, and sustain, this resource. Early work has led to new projects to answer key questions on the interaction of exposures and the development of long-term conditions, thereby enriching the resource. Through MRC-GCRF funding, the cohort is recruiting pregnant women in 2nd trimester from the antenatal clinics in rural and urban health and demographic surveillance site (HDSS) areas, with baseline assessment in consenting mothers and spouses at the participants’ homes. Questionnaires are used to identify common mental and physical health conditions and social determinants (e.g. household characteristics, intimate partner violence, adverse childhood experiences, social support, socioeconomic status). Anthropometry, other physical health measures and, in pregnant women, ultrasound pregnancy dating, are conducted and biological samples obtained. Further participant contacts  at 3rd trimester, delivery, 1, 6 and 16 weeks postpartum, permit collection of repeat mental health and physical measures and biological samples. Infant birth outcomes, growth, body composition and neurodevelopment are recorded along with measures of mother/child interaction. With current funding the cohort is recruiting ~2,000 families with follow-ups to 4m of age. We seek to ensure the continuation and development of Generation Malawi through renewed investment in the core infrastructure, by (i) extending the sample size (from N=2000 to N=5000), and duration of longitudinal assessment (to 3y of age) including key additional measures on child development (ii) continuing the sharable data resource and biorepository, to enable other researchers to respond to multiple complex public health challenges through intervention development and (iii) strengthening research capacity and inclusive in-country engagement to ensure emerging findings feed into timely development and evaluation of interventions. Malawi is a very low-income, high HIV prevalence country undergoing epidemiological and demographic transition. Health resources are constrained. There are no national electronic medical records and access to health services is limited. A large proportion of the population have had sub-optimal early life exposures and experience long-term conditions later in life, both mental and physical. The role of different exposures and environments and the interaction with genetics, and the opportunities for early intervention, are not well studied. Data from urban African populations are particularly scarce. Uniquely this Malawi cohort has both rural and urban elements, and is nested within established health and demographic surveillance sites and long-term conditions (both physical and mental health) cohorts, giving an in-depth understanding of the epidemiology of the key conditions in the underlying population and adult trajectories of health. The cohort is particularly well-positioned to investigate intergenerational effects, to capture mental health, nutritional and cardiometabolic measures in parents and to understand the impact on development in the infant and future risk of long-term conditions. Understanding the intersection of physical and mental health burden, social determinants, nutrition, genetics and environment (including susceptibility to climate change) is critical in these highly vulnerable populations if we are to intervene effectively.

UKRI Gateway to Research · FY 2025 · 2025-01

The notion of symmetry pervades mathematics and physics. Beyond being beautiful, symmetry is often immensely useful: it is a powerful tool that allows us to solve problems. My field of Representation Theory is about the systematic study of symmetry and the various ways it can be applied to problems. Representation theory has grown in stages. The first 70 years of the subject was about fundamentals of symmetry. Starting in the 1960s mathematicians and physicists began to explore the interactions between symmetry and geometry. The subject climbed from dimension zero to dimension one with the introduction of loop groups.  These are symmetry groups extended spatially over a one-dimensional circle (a "loop"). Loop groups have been a phenomenal success: they have a close connection to quantum physics and conformal field theory and they form the corner stone of the Geometric Langlands Program. Starting with the work of Kac and Moody, the subject has been developed to such an extent that it is now a core and mature part of Representation Theory. Starting in the late 1990s is the next step in this ladder: dimension two and the double loop groups, which is one of the most exciting frontiers in representation theory and the topic of my research. Unlike loop groups, the theory of double loop groups is still in its infancy. There are many approaches to double loop groups, and, unlike in the case of loop groups, we do not yet know how they relate to one another. My research program is about three approaches to understanding double loop groups: p-adic loop groups   The p-adic numbers are a number system built for studying arithmetic behaviour focused on a single prime p. A remarkable feature is that p-adic numbers also behave like Fourier series. Therefore, p-adic loop groups are an incarnation of double loop groups. This approach has led to Iwahori-Hecke algebras, and my ongoing work has been about unravelling the mysteries of these groups and associated Hecke algebras. Coulomb branches   Coulomb branches are mysterious spaces arising from the physics of (3d N=4) quantum field theory. Recent work has put them on firm mathematical foundations and also revealed a surprising link to loop groups and double loop groups. They offer another approach to the geometry of double loop groups. In particular, they are the basis of the Geometric Satake Correspondence for loop groups. Here, my ongoing work is about proving the necessary geometric results to carry this out. Coherent categorification   Another approach to Iwahori-Hecke algebras is via algebraic geometry, specifically coherent sheaves on flag varieties. Here my goal is to construct a Hecke category, build an exotic t-structure, and then match the resulting Kazhdan-Lusztig theory to the one I am building using p-adic groups. With my collaborator Kostiantyn Tolmachov, who is an expert in coherent sheaves and Geometric Representation Theory, we have outlined a detailed plan to accomplish these aims. Again, the richness and mystery of the subject comes from the presently unconnected approaches to double loop groups. The goal is to leverage these approaches and develop a geometric theory of double loop groups. As one of the few experts in multiple of these approaches, I am ideally suited to make these connections and drive forward with this research.

UKRI Gateway to Research · FY 2025 · 2025-01

Antibiotics have been used for many years and are central to the treatment of many common bacterial infections1. However, because antibiotics kill bacteria, there is a strong selection for mutants, slightly different from the parental type of bacteria: a new resistant form. These resistant bacteria are no longer susceptible to common antibiotics resulting in an urgent need for new alternative forms of treatment2. Of greatest concern are the Gram-negative family of bacteria that pose the most serious threats to human, animal and plant health. The management and treatment of these infections falls within the "Tackling infections" strategic theme of the UKRI priority areas. The challenge we are addressing is how to treat infections that can rapidly adapt to traditional antibiotics. One possibility is to use anti-virulence compounds that "disarm" bacteria rather than killing them, generating less selection for resistant mutants3. This approach is particularly attractive to deal with toxin-producing bacteria because their treatment with traditional antibiotics is controversial including reports of increased toxin production and more severe symptoms4. By not killing the bacteria, toxin release is avoided. The organism we work on is Escherichia coli O157:H7 (EHEC), a zoonotic pathogen that colonises cattle and enters the food chain causing life-threatening disease and a variety of complications through the production of shiga toxin. There is currently no effective vaccine or antibiotic treatment recommended for the treatment of EHEC infections5. Our group has been working on a "re-discovered" compound called aurodox which was initially characterised in the early 1970s6. Treatment of EHEC with aurodox results in a strong repression of the type three secretion system (T3SS), used by the bacteria as the primary mechanism to attach to host intestinal cells7. Under a nearly completed RCUK grant, we have shown that aurodox can prevent the pathology associated with EHEC infections, specifically shiga toxin-mediated kidney damage and weight loss in mice. This is the first demonstration that aurodox protects against EHEC-type disease in an animal model and paves the way for translation into humans. However, three major questions remain: firstly, how does aurodox work to suppress the expression of the T3SS, secondly, can aurodox be used to treat other problematic infections that also rely on the T3SS for virulence, and, thirdly, can we generate new derivates of aurodox. These three questions are the focus of the current proposal. Why are these questions important to address? Firstly, knowledge of the mechanism of action is an important piece of information that pharmaceutical companies often insist on before they are prepared to invest in clinical trials. Understanding the mechanism helps the further refinement and development of the compound. Secondly, demonstrating the ability of aurodox to prevent infections in other pathogens would widen the commercial potential of the treatment and help attract investment that is essential for translation to the clinic/field. Finally, generating new derivates would provide unique intellectual property and can help increase the potency and specificity of the compound. We also believe the results of this science would generate world-class science that would be of broad interest to the community.

UKRI Gateway to Research · FY 2025 · 2025-01

Disease emergence occurs when a pathogen spills over into and spreads in a novel host population, or when established host-pathogen interactions change, leading to an increase in the incidence and / or severity of disease. The role of biodiversity in disease emergence has been investigated primarily from two angles: First, emergence risk may be exacerbated in areas where host populations of interest about biodiversity hotspots, since these are likely to contain a multitude of candidate pathogens -- some poised for emergence. On the other hand, host diversity may dilute emergence risk for some generalist pathogens, because the most competent hosts tend to be less abundant in diverse ecological communities. As such, in the context of disease emergence, pathogen biodiversity is typically thought to pose a threat, whereas host biodiversity is often considered to offer protection. Since host and pathogen biodiversity are tightly linked, the consequences of biodiversity loss for disease emergence are thus difficult to predict. Here we offer a novel perspective on the links between biodiversity loss and disease emergence: We hypothesize that the loss of pathogen biodiversity may contribute to disease emergence risk, because it reduces the richness of (mild / subclinical) infections by pathogens that are related to, but distinct from the dangerous infectious agents that are most likely to cause disease emergence. Specifically, we posit that exposure to diverse related pathogens prompts hosts to establish multivalent cross-reactive antibody portfolios, which can (i) prevent severe disease, (ii) reduce transmission, and ultimately (iii) limit the risk of emergence of potentially harmful pathogens into ecological niches that they could occupy. If true, these insights could be applied to (iv) design multivalent "portfolio" vaccines, which can provide relatively stable protection against broad viral lineages. We propose to investigate these ideas using East African nairoviruses as a model system, which include important animal (e.g. Nairobi Sheep Disease Virus, NSDV) and zoonotic (e.g. Crimean-Congo Haemorrhagic Fever Virus, CCHFV) pathogens, as well as species not known to cause disease in either host (e.g. Dugbe virus, Macira virus). Conceptually, the plausibility of our hypothesis is supported by examples of human disease emergence (e.g. influenza, monkeypox) driven by a population-level decline in natural or vaccine-induced pathogen exposure. With this study, we hope to contribute significantly in two connected areas of investigation. First, we re-cast competitive exclusion and community invasibility, familiar concepts in community ecology, in the context of co-circulating related pathogens. Immuno-epidemiological models are pivotal here, because they link mechanisms that occur within individual hosts (i.e., cross-immunity among related pathogens) with consequences that play out in host, vector and pathogen communities. As such, the proposed work establishes a versatile, data-driven multi-scale modeling platform to understand how the diversity of related pathogens mediates disease emergence risk. Second, we leverage this new perspective on emergence risk to pioneer a novel approach to vaccine design. Conventionally, vaccines are tightly targeted to prevent infection by well characterized pathogens: a powerful approach, albeit with limitations in the face of novel pathogen threats. Our work evaluates the idea that broadly targeted "portfolio" vaccines could reduce the risk and possible impacts of disease emergence - potentially shifting the role of vaccines in pandemic preparedness from response to prevention.

UKRI Gateway to Research · FY 2024 · 2024-12

The proposal requests seven items of equipment to benefit the EPS research community across the College of Science and Engineering. Items 1-4: A battery test lab comprising a glovebox, potentiostat, battery tester and dynamic climate chamber. Item 5: A Universal Tribometer to carry out a host of mechanical and tribological tests in a single and compact benchtop system. Item 6: A Scanning Probe Microscope incorporating an atomic force microscopy base unit and extensions to facilitate imaging of soft materials, surface conductivities and electric and magnetic fields. Item 7: A Prodigy (N2) BBO-H&F 5mm cryoprobe for nuclear magnetic resonance (NMR). A nitrogen cooled 5 mm BBO cryoprobe to be installed on an existing 400 MHz NMR spectrometer. This broadband probe is capable of observing the most common NMR active nuclei with much greater sensitivity compared to the current probe. This equipment will expand our current capabilities and capacity in materials characterisation and analysis and complement the extensive capability we have within the James Watt Nanofabrication Centre, Kelvin Nanocharacterisation Centre, Geoanalytical Imaging and Spectroscopy Centre, and College Analytical Suite. The core equipment will underpin a large portfolio of research in fields including materials science and engineering, chemistry, healthcare technologies, communications and sensing. The new equipment will be used by researchers across the College, enabled by our easy access model and training support, particularly for early career researchers and doctoral students. As well as bringing new techniques and methods to our existing research, the equipment will enable new research and initiate new collaborations, and will support multiple EPSRC research grants, CDTs, and collaborative research with industry partners. The equipment will enable us to grow existing userbases and initiate new ones, developing researcher and RTP skills and enabling more University-wide and external access.