University of Bristol

UKRI Gateway to Research · FY 2025 · 2025-09

Understanding how memories are formed is one of the foremost challenges in neuroscience. Recognition memory- the ability to remember things you've seen before- is essential for normal everyday living and is disrupted in neurological conditions, such as mild cognitive impairment and dementia. Hence increasing our knowledge of the molecular mechanisms underpinning memory is essential for the identification of novel targets for therapeutic intervention. In this project, we aim to fill gaps in our knowledge about how such memories are formed, and therefore provide essential clues about how this process goes wrong. To fulfil the brain's function of storing memories, neurons undergo extensive plasticity, i.e., they rapidly change their structure and function in response to incoming signals. There are several different types of memory, mediated by distinct forms of plasticity in different regions of the brain. For example, memory of an object's identity requires plasticity in a region called the perirhinal cortex, whereas memory of an object's location requires plasticity in the hippocampus. These types of recognition memory can be formed by seeing the objects for just a few minutes, and require dynamic changes in the synthesis of specific proteins - some increase, others decrease - that are involved in the structure and function of synapses. The molecular mechanisms that fine-tune these changes in synaptic protein synthesis are unclear. Protein synthesis can be controlled by "silencing" of messenger RNA (mRNA) molecules that encode the proteins. Silencing involves a different type of RNA called microRNA and specialised proteins called Argonaute and DDX6, which together bind to specific mRNAs to reduce protein synthesis. How this process happens at synapses quickly and coherently to mediate a particular type of recognition memory is unknown. By asking innovative questions with newly-developed model systems, we aim to define how the synthesis of groups of important synaptic proteins is regulated rapidly and in a coordinated manner to mediate plasticity in the hippocampus and hence drive the formation of object location memories. This aim is underpinned by the following hypotheses, which we will address in this proposal: 1) In response to a plasticity stimulus in mouse hippocampal neurons, Argonaute binds rapidly to a specific group of mRNAs that encode proteins involved in synaptic structure and function. 2) DDX6 confers specificity in the mRNA selection process and consequent silencing. 3) Silencing of the selected mRNAs is necessary for hippocampal plasticity and consequently, for memory of an object's location. Our objectives are to test these hypotheses by isolating and identifying mRNAs that increase their binding to Argonaute and DDX6 within a few minutes after a plasticity stimulus. We will carry out in-depth analysis of the mRNA sequences to define the specific sites on the mRNA where Argonaute and DDX6 bind, and consequently probe the mechanism involved. Ultimately, we will investigate whether preventing the silencing of individual novel genes in mice affects plasticity and memory. This project aligns with BBSRC's 'Understanding the Rules of Life' priority area. By identifying previously-undiscovered gene regulatory mechanisms that are essential for rapid neuronal plasticity, our work will increase our understanding of how we form new memories. Since deficits in memory are symptomatic of numerous neurological disorders and normal ageing, which pose significant challenges to the UK's economy and society, it is essential to understand the mechanisms of memory formation and uncover potential therapeutic targets.

UKRI Gateway to Research · FY 2025 · 2025-09

Context: The global push towards sustainable energy has intensified the need for renewable sources like wind power. However, meeting rising demand requires a significant scale-up in wind turbine production capacity—the International Energy Authority estimates global installed wind capacity must triple by 2030 to achieve net-zero emissions targets. Continuing with current practices makes this goal impossible, posing a significant challenge for manufacturers. The Challenge: Conventional approaches to increase production, like building more factories and hiring more workers, would be prohibitively expensive. Production also relies on a highly skilled workforce that cannot easily be expanded. Additionally, increasing production speed may heighten the likelihood of manufacturing defects, undermining the strength of turbine blades and requiring costly re-works to design specifications on the production line. A new approach is needed to radically increase production throughput while maintaining quality and operational reliability. Aims and Objectives: The BladeUp Prosperity Partnership between the Bristol Composites Institute of the University of Bristol, LMAT, and Vestas aims to revolutionise wind turbine blade design for efficient, scalable production through machine learning-enabled, advanced computer methods. The key objectives are: Develop turbine blades optimised for ease and speed of manufacturing by accounting for defects/variability during the design phase. This will enable faster production with fewer defects requiring repair. Engineer blades with inherent tolerance to manufacturing imperfections and design uncertainty, ensuring reliability over their operational lifetime and eliminating the need for rework. Create a streamlined process to design for right-first-time manufacturing and for rapid introduction of new blade designs into production, minimising costly manufacturing trials. Achieving these goals would enable manufacturers to triple throughput while maintaining quality, with reasonable capital investments and workforce growth. Potential Applications and Benefits: The Partnership outputs will transform fundamental principles of wind turbine blade design, positioning the UK as a global leader in this critical renewable energy technology. Economically, it will create opportunities for workforce expansion and sustainable growth in the wind energy sector, enhancing energy security. Environmentally, accelerating wind power adoption will reduce carbon emissions and mitigate climate change impacts for current and future generations worldwide. More broadly, the novel design approaches could find applications in other sectors relying on large-scale composite structures, such as aerospace, automotive, and marine industries. The cutting-edge composite materials innovations will enable lighter, more fuel-efficient transportation solutions. Overall, our Partnership could catalyse the widespread transition to renewable energy and represents a vital step towards a sustainable future. By addressing manufacturing bottlenecks, it enables wind power to increase its market share and reliably meet clean energy demands as the world pursues an ambitious net-zero agenda.

UKRI Gateway to Research · FY 2025 · 2025-08

Local production, distribution, and reuse of goods facilitated using robot swarms will enable a more sustainable future through the lowering of transport and waste. By powering local communities to be part of the life-cycle and local economy, we can use technology as an equaliser. This vision requires trusted swarms of robots useable out-of-the-box, with little setup or infrastructure. These swarms will become ubiquitous, cooperating with each other and humans. We focus on the core research questions in swarm engineering required to achieve this vision: 1) Beyond minimal robots: How can we design distributed cognition and action for highly capable next generation swarms? Advances in individual robot hardware mean we can now mass-produce low-cost highly capable robots with significant sensing, computation, communication, and mobility. We will develop robot cognition specifically for distributed systems that will allow these robots to react to their local environment in a capable manner, thereby increasing the breadth of swarm behaviours that may emerge and moving them closer to real-world applications. 2) Trustworthy design: How can we enable real-time human monitoring and control of trustworthy swarms? Real-world swarms will need to be useful, and trusted. New metrics for swarm operations, including key performance indicators (KPIs), swarm performance indicators (SPIs), and trust performance indicators (TPIs), will enable the real-time automatic design of swarm strategies for user requirements using Quality-Diversity optimisation of human-readable controllers. We will also design ways to monitor swarm operations, and control their behaviour in real time. Discoveries will be validated using cyber-physical infrastructure for human-centric stories using digital twins, a swarm logistics testbed, and living labs. Living labs are real-world environments where technology can be trialled, in our case the Bristol Robotics Laboratory, and Paintworks neighbourhood in Bristol. We will work with the ESRC Centre for Sociodigital Futures to co-design use cases for city-scale logistics with users, and will engage with policy makers and the public through a dedicated programme of activities. Through this project we also aim to explore translation opportunities including founding a startup. The result of this journey will be the discovery of best practice to responsibly deploy smart machines in cities. This best practice will be shared with the research community through workshops and a new 'real robotics' network, promoting a positive change in the community towards deploying robots in reality (plus component of this fellowship).

UKRI Gateway to Research · FY 2025 · 2025-08

Mechano-transduction is the sensing of mechanical stimuli by cells and the conversion of this information into biochemical cues that can induce a cellular response. Often these stimuli come from the extracellular matrix (ECM), a protein scaffold that forms the structural basis of tissues and determines their properties. For example, the ECM confers tensile strength in tendons and shock absorption in cartilage. Dysfunction of ECM turnover and mechano-transduction together play a key role in the progression of numerous diseases that pose a significant burden on human health. This includes diseases such as osteoarthritis (afflicting ~7% of the global population), fibrosis (contributing to 45% of all deaths in the west) and cancer (causing ~8 million deaths globally each year). In our current ageing populations, the prevalence of these conditions is only set to increase and thus there is a growing need to understand these processes to improve preventative interventions and treatment. This proposal offers an exciting and novel line of investigation into the mechanisms underlying maintenance of tissue health, of relevance to all these diseases and other musculoskeletal disorders. The molecular composition of the ECM is highly specialised in each tissue to reflect function and is regulated and maintained by dedicated cells whose primary purpose is to synthesise and deposit ECM proteins into the tissue. During synthesis, ECM proteins pass through a cellular compartment called the Golgi, which functions as a processing plant, adding modifications to core ECM building blocks before they are secreted. These modifications change the chemistry of the proteins and consequently how they assemble in the tissue. This in turn affects the mechanical properties of the tissue and how tissue-resident cells behave. Golgi function is therefore vital to tissue health and a better understanding of the regulation of this compartment will help to decipher the mechanisms underpinning numerous diseases. One such form of regulation could come from the ECM itself. In current literature, mechano-transduction from the ECM is well-known to influence many vital cell behaviours but very little is known about the impact it has on the Golgi. My hypothesis is that cells can sense the mechanical properties of their environment and, if they need adjusting, can send signals to the Golgi directing it to change the chemistry of newly secreted ECM proteins to remodel the tissue. This proposal aims to address this gap in our knowledge and test my hypothesis by 1) demonstrating that the Golgi can respond to mechanical signals, 2) elucidating the signalling pathways linking ECM mechanics to Golgi function 3) assessing the susceptibility of the musculoskeletal system to Golgi dysfunction in the context of mechanical signalling. The knowledge gained from this proposal will improve our understanding of how cells respond to and influence their environment and how this can go wrong in disease. The work also has the potential to highlight opportunities to modulate ECM quality using load and environmental adaptations, which will support efforts to develop treatments for musculoskeletal disease and improve quality of life through non-invasive means. This will also feed into the growing fields of regenerative medicine and organoid technology, of relevance to biological engineers and translational science. These technologies also have the potential to reduce the use of animals in research and so their development is a valuable investment.

UKRI Gateway to Research · FY 2025 · 2025-08

The proposal aims to answer a fundamental question in evolutionary biology, namely "Did miRNA pathways have a common ancestor, or did they evolve independently in different lineages?" Over the last two decades, it has become evident that microRNAs (miRNAs) play a central role in almost every major biological process in both plants and animals, such as development and cell physiology. Nearly all animal models do not tolerate the loss of essential miRNA pathway components and exhibit severe defects in embryogenesis. The miRNAs have likely facilitated the evolution of spatiotemporal gene expression and cell-type specialisation. However, the evolution of these miRNAs is still a mystery. While we know that they are part of an ancient RNA interference (RNAi) mechanism involved in antiviral immunity, DNA repair and RNA-processing pathways, it is still unclear how this ancient RNAi mechanism became integrated into our post-transcriptional gene regulation. One big question in this area of research is whether miRNAs independently originated in plants and animals or if they share a common origin. Early studies from land plants and bilaterian animals (e.g. insects and vertebrates) suggested that miRNA pathways evolved separately in plants and animals, given the differences between their miRNA systems and the absence of miRNA pathways in certain groups of organisms like fungi. However, our findings in Cnidaria, a group including sea anemones and jellyfish and split from the rest of the animals very early in the evolution, have unveiled striking similarities between their miRNA system and that of plants, challenging the independent origin hypothesis. Building on my early discoveries from cnidaria, I set out to explore the miRNA-mediated post-transcriptional regulation at the root of the animal kingdom. Non-bilaterians, like sponges, comb jellies, placozoans, and cnidarians, represent the earliest forms of animal life, diverging from other animal groups over 600 million years ago. Studying these animals can provide key insights into the early evolution of gene regulation mechanisms. Equally, exploring unicellular holozoans, close relatives of animals, will reveal the biological roles of miRNAs in unicellular organisms, and further comparison to animals will reveal the role of miRNAs in the evolution of multicellularity. My research aims to reconstruct the evolutionary history of miRNA pathways in the animal kingdom. I will focus on organisms with key phylogenetic positions, including early-branching metazoans and their unicellular relatives Ichthyosporea. Together, they will provide comprehensive insights into previously uncharacterised aspects of miRNA evolution and its function in the last common ancestor of animals, providing a deeper and more holistic understanding of how miRNAs have shaped the evolution of complex life forms, offering a broader perspective on their role in both unicellular and multicellular organisms. We will address the following objectives: (1) the evolutionary history of miRNA biogenesis through characterising Argonaute-containing RNA-induced silencing complexes in early-branching metazoans; (2) the evolution of miRNA targets and their global gene regulatory network across unicellular and multicellular holozoans; (3) The mechanisms of miRNA-mediated gene silencing in the last common ancestor of animals. The findings from this research will advance our understanding of the evolutionary history of miRNAs and have broader implications for RNAi-based research and applications. Small RNA research holds immense potential in revolutionising medical and agricultural applications through RNAi. Fundamental biological insights and evolutionary studies are also facilitated by small RNA research, shedding light on gene regulation, development, cell signalling, and evolutionary mechanisms.

UKRI Gateway to Research · FY 2025 · 2025-08

Osteoarthritis (OA), a leading cause of disability worldwide, affects millions of people, particularly older adults, and places a substantial burden on healthcare systems, including the NHS in the UK. Current treatments for severe OA, such as joint implants, rely on standard, one-size-fits-all devices that often fail to meet the specific needs of individual patients, leading to complications like implant loosening, inflammation, or mechanical failure. There is a critical need for personalized medical devices that adapt to the unique anatomy and biomechanical requirements of each patient to improve treatment outcomes and quality of life. However, developing such personalized solutions remains a significant challenge due to the time-consuming optimization of materials and manufacturing parameters, making it impractical for clinical use. This project addresses these challenges by developing an Explainable Artificial Intelligence (XAI)-driven framework to design, refine, and validate personalized bone scaffolds—3D structures that support bone regeneration. The proposed framework integrates artificial intelligence (AI) with additive manufacturing (AM), a 3D printing technology capable of creating customized, high-precision medical devices. While AI can accelerate the development of patient-specific designs, its complexity often reduces transparency, leading to trust concerns among clinicians and patients. The XAI approach ensures that the AI-driven design process remains transparent and explainable, providing clinicians with clear insights into how design decisions are made. The key objectives of this project are: Co-designing personalized scaffolds using an AI framework that considers patient-specific data, such as CT scans and bone density metrics, to optimize scaffold geometry, material composition, and mechanical performance. Refining the design space through iterative simulations that balance the scaffold’s mechanical strength and biological performance, ensuring it meets clinical requirements. Manufacturing and verifying scaffold prototypes using advanced bioprinting techniques. These prototypes will be tested to confirm their biomechanical integrity and biological suitability. Ensuring transparency and trust by providing clinicians with explainable AI outputs, enabling them to understand and validate the rationale behind AI-generated scaffold designs. This project builds on a successful collaboration between the applicant and the Singapore Centre for 3D Printing (SC3DP), leveraging their state-of-the-art bioprinting facilities and expertise in additive manufacturing. Previous work has demonstrated the feasibility of innovative scaffold designs, such as anatomically accurate “bone bricks” with nonuniform pore structures that mimic native bone and show improved mechanical and biological performance. By integrating AI into this foundation, the project aims to address the time and complexity barriers currently limiting the clinical adoption of personalized scaffolds. The potential applications and benefits of this work are substantial. For patients, personalized scaffolds will offer better anatomical fit, improved bone regeneration, and reduced complications, enhancing recovery and quality of life. For clinicians, the XAI framework will streamline the design process, providing trustworthy and efficient solutions for personalized care. Healthcare systems, such as the NHS, will benefit from reduced treatment costs and improved outcomes for patients with bone defects caused by osteoarthritis, trauma, or other conditions. This project also has broader implications for the research community and policymakers, showcasing how AI and advanced manufacturing can work together to transform healthcare delivery. By addressing the barriers of transparency and trust, the XAI approach sets a precedent for responsible and explainable AI adoption in medical applications. Furthermore, the collaboration between UK and Singapore research institutions strengthens international ties and fosters innovation in personalized regenerative medicine.

UKRI Gateway to Research · FY 2025 · 2025-08

We propose to discover and characterize the elusive triplet state in dibenzoterrylene (DBT) molecules using novel sensitizer-enhanced spectroscopy. By combining chemical and quantum optical approaches, we will measure the triplet state's energy structure, develop coherent preparation protocols, and optimize spin coherence times. This work will establish DBT as a promising quantum memory platform while advancing our understanding of molecule-phonon coupling in quantum systems. Single DBT molecules embedded in poly-aromatic hydrocarbon matrices have emerged as exceptional quantum emitters, demonstrating remarkable optical coherence properties at cryogenic temperatures. These molecular quantum systems offer several advantages over epitaxial quantum dots, including their identical nature, ease of fabrication, and opportunities for functionalization. While DBT molecules demonstrate exceptional quantum optical properties, their ground and excited states are both spin singlets, limiting their use in quantum memory applications. A triplet state would provide the desired spin degree of freedom, offering a route to quantum memory in these excellent emitters. The triplet state has remained unobserved due to two key challenges: the difficulty in calculating accurate theoretical predictions of its energy levels, and the extremely weak intersystem crossing rates (approximately 10-7) that make direct experimental detection nearly impossible through conventional methods. We propose a novel approach combining chemical and quantum optical techniques across three main objectives: I. Triplet State Discovery and Characterization: We will employ molecular sensitizers with strong intersystem crossing to enhance population transfer to DBT's triplet state. Using broadband spectroscopy in-solution phase, we will locate the triplet energy level, predicted to lie at infrared wavelengths. This chemical approach circumvents the limitations of direct optical excitation. II. Energy Level Structure, Dynamics and Coherent State Preparation: Once identified, we will employ Autler-Townes spectroscopy to precisely determine the triplet state's energy, spin structure, and linewidths. We will measure the radiative and non-radiative rates of the pathways to and from the triplet state. This spectroscopy will also serve as an excellent test for density functional theory predictions of triplet states in complex molecules. The weak intersystem crossing prevents efficient spontaneous population of the triplet state. We will develop a two-photon coherent Raman transfer scheme to directly prepare the triplet state, enabling controlled access to this quantum resource. III. Spin Coherence Engineering: Initial spin coherence measurements will be performed in a cryostat under high magnetic fields. We will systematically study decoherence mechanisms, particularly focusing on interactions with lattice phonons and surface charges. Drawing parallels with epitaxial quantum dots, we will employ charge engineering techniques and dynamical decoupling protocols to extend coherence times, and photonic engineering to enhance light-matter interaction and branching ratios for chosen decay paths. Our long-term vision is to develop DBT into a quantum memory platform capable of storing and manipulating entangled photonic states through spin operations. Our approach unites expertise in chemical synthesis, ultrafast spectroscopy, and quantum optics to address fundamental questions about molecule-vibration-electron coupling while advancing practical quantum technologies.

UKRI Gateway to Research · FY 2025 · 2025-08

The UK's National Crime Agency has recently warned that nitazenes pose a significant threat. These Novel Synthetic Opioids, like heroin and fentanyls, activate the mu-opioid receptor and are increasingly found in street heroin as supplies of heroin dwindle. Nitazenes are also emerging in party drugs (e.g., Ecstasy, 2C-B), cocaine, and illicit vapes. Several nitazenes are more potent than heroin and fentanyl, posing a severe risk of escalating overdose and death rates among the UK's 300,000 opioid users and over 1 million Class A drug users. Since June 2023, nitazenes have been linked to around 300 deaths, with this figure likely to rise. Particularly concerning is evidence that naloxone, the standard opioid antidote, is less effective at reversing nitazene overdoses compared to heroin overdoses. Currently there are ~40 known nitazenes and new chemical variants continue to appear. Despite their increasing prevalence, our understanding of nitazene pharmacology, including their interaction with opioid receptors and the mechanisms driving their potent effects, remains limited. Addressing this knowledge gap is critical for developing effective interventions and treatments for nitazene-related toxicity. Our project will comprehensively investigate the pharmacology of nitazene drugs through an innovative, multidisciplinary approach. We have assembled a team of 7 Project lead/Co-leads who are all technical experts and world leaders in the field of opioid research. By combining ligand-receptor molecular modeling, in vitro pharmacology, ex vivo brain slice electrophysiology, and in vivo respiratory studies, we aim to uncover the mechanisms underlying the high potency and dangerous side effects of nitazene analogs. Our goal is to provide detailed insights into the molecular interactions, cellular responses, and physiological impacts of these drugs, laying the foundation for the development of targeted therapies to mitigate their harmful effects. Our focus will be on: Identifying the most potent and dangerous nitazenes, and understanding the chemical basis of this potency to assess future risks from emerging nitazenes. Determining which nitazenes require higher doses of naloxone for overdose reversal and explaining the interaction between nitazenes and antagonists at the receptor level. Identifying properties that could enhance antagonist efficacy, aiding in the development of novel antagonists for better clinical reversal of nitazene overdoses. Access to a collaborator's library of ~100 new nitazenes, some with antagonist properties, will support this effort. Whether individual nitazenes, in addition to centrally depressing respiratory rate, also have the potential to cause respiratory muscle stiffness, further restricting breathing capacity. Evaluating whether heroin use or medically assisted treatments offer any protection against nitazene overdose, crucial for assessing future nitazene risks. Our multidisciplinary approach will be informed by real-world data from our partners at the Bristol Drugs Project, and aims to build a comprehensive model of nitazene action from molecular to systemic effects. Through this, we hope to inform better strategies for prevention, treatment, and harm reduction.  

UKRI Gateway to Research · FY 2025 · 2025-08

Context A personality disorder is a type of mental health condition where a person's way of thinking, feeling, and behaving differs significantly from what is normal in their culture. These differences can lead to severe difficulties in relationships, work, and daily life. About 1-in-12 people in the general population have difficulties associated with personality disorder. The condition is linked to high levels of distress, reduced quality of life, substantially reduced life expectancy, and high costs to health services.   The challenge the project addresses Currently, the causes of personality difficulties and personality disorders are poorly understood. Many people with the condition have experienced trauma in childhood, and treatment and research has mainly focussed on supporting people at an individual level. However, it is likely that there are wider environmental factors that influence whether people develop personality difficulties. These include the type of neighbourhood that people grow up and live in. We already know that this plays a key role in the development of other mental health conditions, such as psychosis and depression. Factors that may be important include deprivation, housing quality, population density (how many people live in an area), local crime levels, and air pollution. It is possible that these also contribute to the development of personality disorders, but we do not know this.   Aims and Objectives The overall aim of my fellowship is to look at the role that neighbourhood factors may play in the development of personality disorders, and also less severe, but important personality difficulties. The project will include three studies. Study 1) I will search medical databases to find all published studies that have previously looked at neighbourhood factors linked to personality disorder. I will bring all of this information together to help me to decide how to carry out the next two studies. Study 2) I will look at the anonymous health record data of people who have received mental health treatment in a large London mental health trust. I will look at the numbers of people diagnosed with personality disorder from areas with different levels of deprivation and other neighbourhood factors. This will help me to understand which neighbourhood factors are associated with the diagnosis. Study 3) I will use information from an existing study of people born in Southwest England, who have been followed-up since birth at several different points throughout their lives. I will see if the neighbourhood where people grow up is linked to personality difficulties in adulthood, and which factors in the environment could be contributing.   Potential applications and benefits This project will fill a gap in our understanding of the causes of personality difficulties and disorders. People diagnosed with personality disorder are often heavily stigmatised. Improving our understanding of how social factors contribute, could reduce the stigma associated with the condition. By helping us to understand more about neighbourhood factors, this project will also inform future health policy on personality disorder. This could include strategies to prevent personality difficulties from developing in the first place. In other mental health conditions this includes improving housing, parenting programmes, or improving the quality of the neighbourhoods that people grow up in. It could also help us target services to the areas they are needed most. This type of ‘population-level’ approach could reduce inequality and ultimately could be more cost-effective than current care.

UKRI Gateway to Research · FY 2025 · 2025-08

The applications of Quantum Information Science (QIS) are rapidly expanding beyond quantum computing, with their phenomena being proposed as ripe for exploration within the field of Chemistry, and how they may revolutionize our understanding of existing chemical reactions and lay the foundations for new syntheses. Important photochemical reactions, key to all life on Earth, have spin-selective photoproduct quantum yields that cannot be explained using a classical theoretical framework. QIS phenomena are implicated, but direct experimental evidence remains elusive. New ultrafast experimental techniques will be innovated to overcome this significant obstacle and unravel: how the quantum mechanical nature of photoproducts remains correlated with the initial photoprepared species; electronic coherences and correlations between photoproducts; how the potency of different entangled photoproduct spin states controls the outcome of chemical reactions in solution. Photoinduced ligand-ligand charge-transfer and photoionization reactions– critical processes in photocatalysis and protein damage, respectively– both initially form charge-transfer products comprised of a spin-correlated ion-radical pair (SC-IRP). Each ion has an unpaired electron that can take two different configurations, e.g. two different spin states. As these are binary states, and spin-coherence is long-lived, each radical ion can be considered as a qubit. Spatial confinement of the two ions will inevitably lead to spin-exchange and generate entanglement within the ion-radical pair. This key quantum property will dictate subsequent reverse reactions to regenerate the parent species, biasing either as singlet or triplet pathways. In systems we have studied, we have shown that this occurs with non-statistical yields, necessitating quantum correlations between precursor and products. Uncovering these key details requires an optical readout of the dynamics to go beyond the current state-of-the-art magnetic resonance methods, requiring the innovation of new two-dimensional femtosecond experimental techniques. Observation of these QIS in Chemistry phenomena will both utilize existing capabilities and require new technical innovations to develop novel ultrafast 2D experiments. These will extend capabilities to deep-ultraviolet (DUV) wavelengths with ultrabroad bandwidth and ultrashort time resolution, which has hitherto proven exceptionally challenging. This will yield world-class 2D electronic and 2D electronic-vibrational spectroscopy (2DES and 2DEV, respectively) experiments with DUV capabilities necessary for studying one set of exemplar SC-IRP system. These advances will only be possible by utilizing the expertise of both Bristol and USC ultrafast spectroscopy groups and their long-established collaboration. 2DEV studies will identify unique infrared spectroscopic signatures of triplet and singlet SC-IRP species in key chromophores of aromatic amino acids. It will reveal their formation timescales, and correlations with the initial electronic excitation in species where unique optical transient signatures are often hard to discern. Further, such experiments will determine the spin-dependent spatial delocalization of excited state wavefunctions. 2DES spectroscopy will investigate electronic coherences in aromatic amino acids and photosensitizers, and how spin correlations are transferred into, and persist, between photoionized products. Such data will reveal the degree of singlet-triplet mixing and the energy gaps between the two states. Critically, these experiments will also reveal whether specific quantum spin-states are more potent redox agents in a novel photocatalytic system. This project will unravel the frontier QIS phenomena underpinning photoinduced directionality over product branching. It will enhance international collaboration by exchanging ideas, advanced technical expertise and personnel between the US and UK. These studies will inspire discovery of novel photochemical syntheses and potentially enable the use of photoexcited states as quantum sensors.

UKRI Gateway to Research · FY 2025 · 2025-08

This project brings together two emerging and under-researched frontiers of knowledge: 1) the 'global development turn', which calls for a movement away from traditional North/South framings and practices of international development towards a more global (though unevenly distributed) understanding of challenges; and 2) the emergence of 'new' or unconventional water, such as desalination and wastewater reuse to address chronic and worsening water challenges in the context of growing demand and climate change. The main objective of the project is to critically assess how new water resources are being used to address water challenges, and in turn, to analyse how they are shaping development opportunities. Original data will be generated through indepth research in two transitioning African countries: Kenya and Morocco, which are both for different reasons turning to unconventional water to address entrenched water-related constraints. The case study research will be complemented by analysis of the new water industry, which is growing rapidly, is global in scope and increasingly looking for opportunities to expand financialised 'solutions' into countries in the Global South. Conceptually, the project advances current debate between planetary and situated forms of knowledge and theory by addressing the tension between context-specific water challenges rooted in colonial history and global flows of finance, technology and knowledge. The project develops a multidisciplinary and mixed method approach that will advance knowledge in the fields of geography, development studies and sustainability studies. The research team will be led by me, as PI, and will include two RAs on 4-year contracts, a PhD student, along with other collaborators, mentors and advisors. The methodology is rooted in the principle that the decarbonization and decolonization of academic knowledge are inseparable moral imperatives.

UKRI Gateway to Research · FY 2025 · 2025-07

Food and healthcare are the foundations on which our current quality of life is built. The pressure on these resources will only increase as the UK population ages, the global population reaches 9 billion in 2050 and the worst effects of climate change begin to manifest. Now more than ever, new medicines and agrochemicals will be vital in combating the growing and evolving threats that face society. A major challenge to the development of new medicines and agrochemicals is the high attrition rate of the candidate molecules being investigated, which drives up the financial cost, environmental impact and time associated with bringing a new product to market. Methods that allow rapid cost- and resource efficient preparation of desirable candidate molecules are therefore extremely valuable. This programme will deliver a suite of synthesis methods to streamline the discovery and development of the next generation of agrochemicals and pharmaceuticals. Building on our recent discovery, we will develop new ways of making valuable molecular architectures while minimising the number of chemical operations required and avoiding the use of toxic or precious elements. By working in close collaboration with leading innovators in crop protection (Syngenta) and human healthcare (AstraZeneca, Pfizer and Carbometrics), we will ensure that our methods will be of direct and immediate benefit. We will also seek to make the reagents we develop commercially available, thus further enabling the rapid and barrierless uptake of our methods.

UKRI Gateway to Research · FY 2025 · 2025-07

Modern technology, from smartphones to particle accelerators, is rooted in the discovery of new materials with unique properties, such as semiconductors for computing devices and superconductors for medical magnetic resonance imaging. Many of these transformative technologies originate from the exotic properties of quantum materials (QMs). To design QMs with desirable properties, it is essential to understand their microscopic mechanisms. Exotic properties and new states of matter emerge from the collective and organized behaviour of electrons. Consequently a widespread endeavour is underway to deepen our understanding of emergent quantum states. The study of topology, magnetism and strongly correlated electrons were initially separate fields. Until recently, the integration of these three fields has revealed exciting potential for physics. A promising way to achieve correlated topology is to identify QMs with geometrically frustrated structure. The kagome lattice inhibits the free movement of electrons, enhancing the electron-electron interaction and leading to diverse quantum phenomena: electron correlations lead to unconventional charge orders, Dirac fermions lead to topological states of matter, and local magnetism is putatively induced by loop currents. This lattice connects atomic structure with quantum phenomena, advancing our ability to create materials with desired quantum properties. The tunability of kagome materials (KAMs) adds another dimension to control the spin-orbit properties and electronic states. Now the investigation of KAMs has become an exciting frontier of condensed matter physics, filled with opportunities but confronted with significant challenges: the order parameters of quantum states are undefined, their responses to external excitations are unclear, and the nature of loop currents in unknown. Current scanning tunnelling microscopy (STM) research on KAMs is limited by studies at 4 K (low energy resolution), using metallic tips (failed to detect subtle electronic states), and employing uniaxial magnetic fields (no influence topological states). To address these challenges, my proposed research will focus on exploring KAMs employing beyond state-of-the-art STM techniques under extreme conditions. My STM features millikelvin temperatures to achieve ultrahigh energy resolution, vector magnetic fields to manipulate topological states, and tips integrated with optical fibre to investigate dynamics. I will apply fields, light and heat to tune the quantum states and simultaneously measure their order parameter to understand their dynamics. My technique's exceptional precision and speciality provide unprecedented detailed observation of unconventional charge orders, topological bands and loop currents. I will study three representative classes of KAM including the kagome metal AV3Sb5, the Weyl semimetals Co3Sn2S2 and the Chern magnets RMn6Sn6. This project, rooted in recent developments in correlated electron systems, new topological materials and STM technology, positions my work at the cutting edge of physics, representing an overarching convergence of modern techniques and concepts. This project focuses on atomic-scale visualization and control of quantum mechanics. Gaining insight into the microscopic mechanisms paves the way for connecting the quantum states at the atomic-scale to emergent novel properties and for engineering materials by design. I will guide material synthesizers on the impact of atomic-scale inhomogeneities on electronic structures and advise on refining edge structures to improve the stability of topological states. The spin-orbit coupling make KAMs promising materials platform for developing scalable devices in spintronics. The topologically protected states make the kagome magnet an ideal candidate for topologically protected quantum memory in quantum information. The quantum effects to be uncovered may underpin future technologies in the latter half of this century.

UKRI Gateway to Research · FY 2025 · 2025-07

The aim of this application is to equip the University of Bristol’s light microscopy facility (Wolfson Bioimaging Facility, WBF) with a multipurpose spinning disk imaging system to meet the needs of a broad range of innovative, discovery research projects. The WBF provides an extensive userbase (currently >350 researchers from >120 groups) in the University of Bristol, and the South-West via the GW4 alliance (Universities of Bath, Bristol, Cardiff and Exeter), with affordable access to state-of-the-art light microscopes and support from RTP experts in image acquisition and analysis. The proposed system will expand the functionality and capacity of the facility to provide cutting-edge techniques to this diverse userbase. Spinning disk microscopy offers advantages for live imaging since, in addition to its optical sectioning capabilities, it is an inherently fast and minimally damaging technique. The inclusion of three additional features greatly enhances the toolbox our users will have at their disposal to study biological processes at high speed and in great detail: Photomanipulation to probe the dynamics of intracellular components and individual cells, and photodamage to study the responses to localised cell destruction. High-content screening (HCS) enabled by multi-well imaging and AI analysis tools to increase the throughput and efficiency of data acquisition and analysis. Extending the range of available lasers to expand the number of targets that can simultaneously be observed during imaging — increasing efficiency and expanding labelling options for researchers. We anticipate heavy use of this system immediately following acquisition and for many years to come. An initial user base of 24 research groups that fit squarely within BBSRC priority research areas (especially fundamental biosciences and engineering biology), of which 16 have been selected as co-leads, have projects which would immediately benefit from access to this technology. The projects will advance our understanding of the dynamic processes which are fundamental to the rules of life. These include study of intracellular transport, cell signalling, organelle plasticity, neurological development, tissue engineering, development and repair, tumorigenesis and the development of novel antimicrobials. Beyond these immediate users, the WBF provides expertise and assistance to researchers within the university and South-West at affordable prices in a sustainable costing model — widening access to users with any level of experience. In summary, the proposed multi-purpose spinning disk system would address critical shortages of key imaging capabilities in advanced live imaging, high-content screening and multiplexing required by diverse groups of researchers across the University of Bristol and beyond. These cutting-edge tools will be supported by a well-established facility with a high level of technical expertise and a proven track record of supporting pioneering research.

UKRI Gateway to Research · FY 2025 · 2025-07

This proposal brings together molecular cell biology and protein design to understand, manipulate and target a fundamental mechanism that controls how cells are organised. Cells possess many specialised components that must be in the right place at the right time to fulfil their functions. After their use, these components must be transported away for recycling or degradation. In addition, cells must adapt their organisation to meet functional demands or respond to changes in their environment. Mis-regulation or disruption of transport processes can contribute to human neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS) and Alzheimer's Disease. In addition, cellular transport machinery can be 'hijacked' during viral (HIV-1) or bacterial (Salmonella) infections. Therefore, interrogating these transport systems is key to understanding the natural workings of cells, diseases, and infections. To move components around, cells use a transport system composed of a network of dynamic cables known as microtubules. Much like a railway network, these cables link together regions of the cell. Cells also possess 'vehicles' that travel along this network known as motor proteins. One of the most important is a family of protein complexes known as kinesin-1, which are the subject of this proposed study. Motor proteins can selectively attach to specific components inside cells and move them by walking along the microtubule network. Despite the importance of motor proteins across many areas of cell biology, we lack a proper understanding of how these complex machines are controlled. This proposal is all about understanding and exploiting this control within cells. Control is achieved by changes in the shape of the kinesin protein complex: it folds over allowing one part of the protein to reach around and jam the mechanism that allows the vehicles to move - this is known as autoinhibition. Our recent BBSRC-funded work (BB/W005581/1) has established some new key principles for how this works. The next step is to understand how the complex is unjammed and activated at the right place and time. We propose that this process is allosteric - where the activity of kinesin-1 is controlled by means of a conformational change induced by a different molecule(s). This proposal focuses on understanding that molecular mechanism. Our recent work also demonstrates new opportunities to design molecules that may enable intervention in transport processes. In this proposal, we ask: can we make the motor do more work, less work, or direct its activity to specific jobs? Eventually, we want to explore if and how these ideas transpose to kinesins and the diseases they are implicated in. To do this, we will develop the capacity to acutely and specifically control kinesin activity using small fragments of proteins called peptides. If successful, the impacts would extend well beyond the kinesin-1 field because the mechanisms we seek to target are ubiquitous throughout cell biology. Together, this research addresses cutting-edge fundamental cellular dynamics and sits squarely within the frontier bioscience and understanding the rules of life remit of the BBSRC. Moreover, aligned with the UK National Vision for Engineering Biology, by employing protein design, it applies insights from complex natural systems to develop a quantitative understanding and new biological tools for engineering-biology and biomedical applications.

UKRI Gateway to Research · FY 2025 · 2025-07

We are applying to run a short course in application of quantitative X-ray microanalysis (QXRM) techniques for PhD students and early career researchers (ECRs) in Earth and Environmental Science. It is based on several previously successful NERC sponsored courses, most recently in 2023 which this course largely repeats. It consists of a 3.5 day taught unit in the Electron Microbeam Laboratories of the School of Earth Sciences, University of Bristol, and then followed by part 2 where each participant has 2 days of one-to-one hands-on instruction in the analytical laboratories at one of Earth Science schools in Bristol, Leeds, Oxford, Cambridge or Manchester depending on the particpants' location in the UK. We will accommodate 25 students and ECRs on the course. Selection of applicants is based on evaluation by members of the course team of a brief proposal anonymised other than identifying the funding source where priority is given to NERC and other UKRI research council funded people. QXRM methods are, by their nature, complex and require users to possess a significant degree of training if the full advantages of these techniques are to be realised. UKRI, and NERC in particular, have significant investment in QXRM facilities including in this application’s host institutions. We recognise an urgent need to train the next generation of Earth and material scientists partly driven by the lingering effects of COVID on a cohort of PhD candidates, and subsequently ECRs, who missed significant on-instrument training opportunities with a consequent impact on their productivity.  This results in a significant depreciation of national capability, both in terms of users who have can produce high-quality data and also end-users of published data who require an ability to interpret and filter out poor data.  Importantly, there is a demand from industry for trained users, with SEM/EPMA techniques hosted by both government (e.g AWE, Aldermaston) facilities and private industry (e.g. Johnson Matthey for critical metals analyses).  Furthermore, the advent of rapid mineral modal analyses via electron microscope-based systems has been widely adopted by both industrial (e.g. mining and forensic) and academic organisations. We recognise six primary training outcomes are: 1) Students will be able to demonstrate an understanding of the fundamental physical principles of QXRM; 2)Students will be able to design their own analytical protocols and apply to a range of multi-disciplinary projects, 3) Students will be able to model the X-ray generation within samples using complex simulation software, 4)Students can perform post-processing operations on both mapping and quantitative data, 5)Students can calculate statistical parameters, of errors and homogeneity of sample analyses; 6)Students will have an understanding of the broad applications of SEM/EPMA in industry (skill 5). In addition to the identified skills gaps, applications of QXRM cover many expanding fields of NERC’s wider science remit beyond the more conventional geosciences and indeed several other areas outside the NERC remit.

UKRI Gateway to Research · FY 2025 · 2025-07

Connected Earth aims to empower 11-to-17-year-olds from deprived socio-economic backgrounds to explore and voice their concerns about the future of their environment, and to connect these young people with scientists, activists and practitioners with similar lived experience who are successfully addressing the environmental challenges that they face. Today’s young people (YP) stand to inherit a world with increasing global temperatures, burgeoning demand on Earth’s resources and more intense environmental hazards. These emergent crises stand to disproportionately effect the most deprived communities. Many YP are in challenging circumstances which prevents them from engaging with climate science and wider environmental work. In addition, the ways they can contribute to positive change whilst also making a living from environmental work can appear limited, as there are so few visible role models. These barriers and perceptions compound to make the environmental sector less appealing to YP from underserved backgrounds relative to other career paths. Connected Earth will address these barriers through six workshops in which groups of ~20 YP co-produce podcasts with local environmental leaders across three themes: climate change and biodiversity loss, Earth’s stretched resources and intensifying environmental hazards. The themes match key components of the National Curriculum for KS3-4 and cover key skills gaps in the UK’s environmental sector. The workshops will support YP to build climate literacy and the skills needed to address environmental challenges, gain confidence voicing their opinions and experiences of environmental change and develop interventions needed for environmental solutions that also meet their community’s needs. The YP will record audio of conversations based on their findings from the workshop alongside two local environmental leaders (“Ambassadors”) who share the same lived experience and who currently work in the environmental sector across science, nature-based solutions and activism. The Ambassadors will be identified through the networks of Bristol Climate and Nature Partnership and our existing partner organisations. Ambassadors will highlight their diverse pathways into environmental careers, ahead of the YP choosing GCSE and A-level options that suit their aspirations. From the audio we will create podcasts to be shared with the workshop groups, their schools, and be distributed more widely through our existing network of partners, teachers and social media. We will also create lesson plans and activity sheets to be shared via the Teach Earth network, so the workshops can be used by other schools in their teaching. Through this flipped approach to engagement, Connected Earth aims to foster hope among YP about their future, establish visible role models and highlight diverse pathways into the environmental sector. We will deliver the workshops in partnership with Bristol WORKS – a non-profit that supports YP at schools in Bristol that have multiple indicators of deprivation into post-16 pathways. Ultimately, Connected Earth aims to establish a sense of ownership of solutions to environmental challenges amongst disenfranchised YP, to influence early decision-making against the sciences at GCSE and A-level, and thereby impact their ability to choose environmental career paths in the future. We envisage that the place-based approach of Connected Earth can be scaled-up to a national program and will conduct rigorous self-assessment of our pilot and generate a set of recommendations for such a program.

UKRI Gateway to Research · FY 2025 · 2025-06

Dengue virus (DENV), a member of the flaviviridae family, is the cause of mosquito-borne dengue fever. Endemic in 100 countries, it leads to over 400 million infections and 25k deaths annually worldwide. With no effective treatments or vaccines, it represents a major socio-economic burden for tropical and subtropical developing countries. Expansion of dengue Aedes mosquito vector due to climate change makes it increasingly a global threat, with over 4 billion people at risk, including EU and UK. There is an urgent need for detailed understanding of the DENV lifecycle for devising new pathways for tackling DENV infections. Central to DENV's lifecycle is its replication, a process that has been very recently linked with lipid droplets (LD; ubiquitous multifunctional intracellular organelles of 0.05-100 um in size), with DENV capsid proteins (DENV-C) found accumulating on LD, leading to nucleocapsid formation and viral particle self-assembly. Critically, this process is initiated by the adsorption of DENV-C onto the LD surface mediated by molecular interactions between DENV-C and the LD membrane and surface-anchored proteins, particularly Perilipin 3 (Plin3). Of particular interest to the molecular interactions is an intrinsically disordered region (IDR), i.e. the first 30 amino acid residues at the DENV-C N-terminus. Probing these fundamental molecular interactions, using a combination of physicochemical experimental and computer simulation methods, is the focus of this proposal. Our approach to designing the experimental programme is guided by the following considerations. The molecular interactions - electrostatic or hydrophobic - depend intricately on the amino acid sequence in DENV-C IDR. We thus will leverage advanced peptide synthesis to precisely tailor IDR-analogous viral peptide sequences and compare them with full IDR and C-proteins. The inherent complexity in LD obscures mechanistic probing of the underpinning molecular interactions. We thus will leverage biophysical methods to establish LD models, incorporating Plin3 and essential LD surface structural and compositional features. Going beyond phenomenological observations, we will bring to bear quantitative experimental and computational methods in biophysics and surface science to directly access molecular structures and interactions at complex interfaces.

UKRI Gateway to Research · FY 2025 · 2025-06

Rationale. Current indicators used in national river health assessment systems (e.g. EU WFD) do not reflect well the structure and function of aquatic ecosystems and are very difficult to translate into aquatic ecosystem services as needed for new EU and global policies. Vision. BREATHE's main objective is to co-design with stakeholders a multiscale (river basin to global) sensor-based River Observation System (RIOS) including dissolved oxygen and whole river metabolism to quantify aquatic ecosystem services such as climate regulation, water purification, and habitat suitability. Action. BREATHE will co-design a workflow from data sources to oxygen indicators, river functions and aquatic ecosystem services. BREATHE will work in six countries across a latitudinal and elevational gradient spanning neotropical to alpine climate. Relevance to the call BREATHE addresses Theme II of Water4All Strategic Research and Innovation Agenda (SRIA) 2022-2025, notably Theme II.I Functioning and Biodiversity, II.II Resilience, mitigation and adaptation of aquatic ecosystems and ecosystem services to global changes. BREATHE will provide tools for water management (Sustainable water management Theme III.V), including trans-boundary cooperation (International cooperation Theme VI.II) and enhancing the regulatory framework (Governance Theme VII.III). BREATHE will address the river basin scale perspective in the co-design of river observation systems and coconstruction of case studies. BREATHE's main goal is to establish an international River Observation System and thus responds mostly to Topic 1. Mapping, monitoring, and assessment for a better understanding of ecosystem services [...], and more specifically 1.2 Supporting a transnational network of harmonised monitoring schemes building upon the work conducted under other initiatives and previous EU projects. BREATHE will develop a workflow from data sources to river functions and indices to ecosystem services for policies, integrating a modelling component and case studies with multiple stressors, thus responding to Topic 2. In particular, BREATHE will use advanced methods and techniques to characterise the response of rivers to multiple pressures, provide mechanistic understanding, and predict the consequences of these impacts - response relationships on ecosystem services (tackling Topics 2.3 and 2.4). BREATHE will provide new tools and solutions (see WP2) which can be used to better integrate ecosystem services into the management of water resources (Topic 3, notably 3.1 Innovative management and governance strategies for integrating ecosystem services into conservation policies and restoration measures).

UKRI Gateway to Research · FY 2025 · 2025-06

Title Safely and quickly introducing and testing new surgical procedures and devices. Background Surgery is an essential part of the National Health Service (NHS). Developing surgical innovations (new surgical procedures and medical devices used within the body) is important to improve patient care and hospital efficiency. There have been big advances over the past two decades with innovations such as robotic and keyhole surgery, and the future holds more change. Despite this, serious patient harm has been caused. This is because surgical innovations are used on patients without research happening soon enough. These problems have been identified by a national safety review, by the UK General Medical Council, and by investigations our research team have undertaken. All agree urgent changes are needed. Aim This project will develop a new approach (a new method), to help surgeons and researchers design and safely conduct early research studies of surgical innovations. The method will: Involve research within the development of surgical innovations so that they can be tested earlier, and fewer patients are given unsafe or untested procedures. Ensure that surgeons understand how to test surgical innovations safely and fairly, without personal bias. Help surgeons and healthcare providers make better decisions about when to continue, change, or stop surgical innovations, based on more reliable information. Enable surgeons to study which patients are most suitable for surgical innovations, so that they can be offered to all appropriate patients. Prevent delays to future studies that will help the NHS decide whether the surgical innovation should be used more widely. Approach So that the method meets the needs of all relevant people, we will involve stakeholders in our project. This includes surgeons, patients, researchers, people from the NHS, medical organisations, device manufacturers, regulators, and funders of surgical research. Our project involves three pieces of work: Firstly, we will hold stakeholder interviews and workshops to develop a draft method. Secondly, we will explore how the method is used in real-life research studies of surgical innovations in NHS hospitals. This will examine how practical and acceptable to surgeons the method is and improve it. Thirdly, we will produce and share a report with our stakeholders on the method and how it may be tested in the future. Our project was developed with input from patients and the general public, who agree it is important and have helped shape it. We will continue to involve patients and the public throughout the project. We will share our findings with all stakeholders through scientific journal articles, meetings, patient groups, websites, and social media. Potential benefits Our project will improve how surgical innovations are developed and tested in the NHS by developing a new method for testing them. This will help surgeons use surgical innovations safely because the method will create reliable information about their benefits and harms. Patients will benefit by having harmful or ineffective treatments abandoned sooner and safer, beneficial treatments made available sooner.

UKRI Gateway to Research · FY 2025 · 2025-06

Adolescence is characterised by pubertal growth spurts in height and weight, and rapid changes in body composition. These growth patterns can be influenced by early life factors (e.g., prenatal stress, famine, war, recession) and can have consequences for adult health (e.g., obesity, diabetes, cardiovascular disease, osteoporosis). The SITAR (Super Imposition by Translation and Rotation) method of growth curve analysis summarises individual growth patterns using three parameters (size, timing, and intensity) that are estimated as random effects, plus a cubic spline estimate of the average growth curve. SITAR was designed to simplify the analysis of adolescent height growth curves in individuals and explains >99% of the age-specific variance in height, making it an accurate and efficient method to summarize individual growth trajectories   SITAR random effects can be analysed further in relation to earlier growth-altering exposures or later health outcomes, making the model highly relevant for translational medicine and life course epidemiology. However, these analyses are often performed in two stages–first estimate the random effects, then relate them to the exposure/outcome. This two-step approach leads to biased estimates of the association as it ignores the underlying random effect error structure. Moreover, SITAR assumes a plateau or constant growth at the end of the growth spurt which means it does not properly fit outcomes that continue to change, and at different rates, going into adulthood (e.g., weight, adiposity, lean mass, and bone mass).   The aim of this project is to facilitate unbiased analysis on determinants and outcomes of height and body composition growth around adolescence and emerging adulthood and empower researchers with essential information and tools for the best-practice analysis of individual growth patterns and their correlates. The project will address the limitations described above by (1) tackling the outstanding methodological issues, (2) developing open-source software to implement the new insights and (3) creating resources to guide researchers with implementation and interpretation of the methods.   Methodological developments include methods for joint models to simultaneously estimate SITAR growth features as exposures and the effects of those features on later outcomes. Complementary developments include revising SITAR to effectively quantify variability in post-peak growth rate and to accurately fit weight, adiposity, lean mass, and bone mass growth curves. The new methods will be tested using repeated growth measurements from age 5-20 years in four well-established prospective cohort studies in the UK, USA, and Canada, and using simulation studies. New R packages, a workshop, and interactive guidance material will enable statisticians and epidemiologists to apply the method relatively simply, including in multicohort study settings, and to interpret the results appropriately. This project makes an important novel contribution to modelling of longitudinal growth measures and will significantly increase our understanding of the determinants and outcomes of growth in adolescence and emerging adulthood. Together, the methodological developments will facilitate unbiased state-of-the-art analysis of individual growth curves and their correlates and make this accessible to researchers.

UKRI Gateway to Research · FY 2025 · 2025-05

From the motion and self-organisation of microscopic biological organisms to the formation of galaxies, far-from-equilibrium physics is a ubiquitous feature of the natural world and a grand challenge in contemporary physical science. Despite myriad examples in science and engineering, there is a relative paucity of established theoretical frameworks to describe non-equilibrium phenomena, in particular those that rationalise universal features across multiple length- and time-scales. Over the last two decades the field of active and driven matter has been the target of intense research focus, in part due to its success in describing myriad biological phenomena and its close connections with soft matter physics. Active systems, such as swimming spermatozoa or flocks of fish and birds, operate far from equilibrium by converting an internal energy supply into mechanical motion that can in turn lead to dramatic and unexpected collective motion. From an experimental perspective, however, biological systems are difficult to control and contain multiple interacting physical processes whose role in the observed dynamics of the system are difficult to quantify. To overcome these difficulties synthetic and artificial experimental systems are gaining popularity due to their high degree of accessibility and parametric control. Among this family of experiments are hydrodynamic systems that are driven out of equilibrium by external forcing of the environment. When particles or objects are placed in these complex flows, they exhibit behaviour that is reminiscent of the random or stochastic dynamics of biological organisms thereby challenging fundamental assumptions of smooth-particle hydrodynamics and in turn forging hitherto unrealised connections between classical fluid mechanics and statistical physics. Driven hydrodynamic systems thus serve as a promising candidate to identify universal features of active and driven matter across scales, with mathematics serving as a bridge between these disparate systems. Identifying such commonalities is an essential task in establishing the much-heralded usefulness of active and driven matter in real-life engineering contexts. The aim of this project is to consider a particular example of a driven hydrodynamic system that explores the dynamics and emergent statistics of floating bodies placed in a field of fluctuating interfacial Faraday waves. The Faraday-wave system is supplied by a practically inexhaustible source of energy and emergent dynamics can be explored over significantly broader parameter regimes in contrast to living systems. The research proposed herewith is anticipated to have far-reaching consequences beyond the realm of active and driven matter. In particular, our lab-scale experimental system promises to shed new light on how large plastic particles are transported and distributed in wavy and turbulent fluid flows, a fundamental challenge in climate-change research and oceanography. Furthermore, the dynamics of many non-equilibrium systems are complicated by the presence of memory wherein the future trajectory of the system is intimately tied to its past. An understanding of such temporally correlated, non-Markovian transport processes remains in its infancy in contrast to its Markovian counterpart. Our fully integrated experimental and theoretical approach is thus uniquely placed to make significant contributions to addressing this major unsolved problem in statistical physics.

UKRI Gateway to Research · FY 2025 · 2025-05

Explaining animal cooperation has been a central ambition of biology since Darwin. We now know that climate plays a crucial but mysterious role in social evolution: comparisons across the planet (in birds, insects, and mammals) have found that the distribution of cooperative species is linked to climatic factors, including aridity and unpredictable rainfall. However, it remains unclear why these global patterns exist. How is cooperation among individuals directly influenced by climate? Solving this riddle demands high-resolution, within-species studies across climatic zones, including rigorous experimental tests in the wild. This project will establish the largest within-species study of cooperation ever attempted – combining field experiments, longitudinal observation, theoretical modelling, and integrative studies of neuroanatomy, gene expression, and morphometrics in a powerful new system of social wasps that span a vast climatic range of more than 5000 km across Sub-Saharan Africa. For decades, the strongest arena for uncovering the rules governing social behaviour has been ‘cooperative breeding’ (animals raising others’ offspring). Exploring cooperative breeding has transformed biology, ultimately leading to the general theory of behaviour that now underpins our understanding of all life on Earth, from bacteria to baboons (‘inclusive fitness theory’). Among cooperatively-breeding animals, Africa’s long-neglected but widespread wasps (Belonogaster juncea) are ideally suited for uncovering the links between climate and cooperation. From arid deserts to lush rainforests, they inhabit an extraordinary diversity of climates. They offer small, manipulable groups (individuals can be removed and added), high replication (often hundreds of nests within a few kilometres), ready dissection, and easy observation (allowing tracking of individuals over time and space). Because we have already conducted pilot studies (confirming wasps respond to manipulation and generating promising genetic results), obtained research permits, and established local collaborations in three African countries (Cameroon, Kenya, South Africa), we are well-placed to study cooperation at this unprecedented continental scale. We will tackle four objectives, targeting 140 sites across Africa that span wide spectrums of aridity and seasonality. First, we will reveal whether aridity amplifies the value of cooperation, conducting field experiments in rainforests, savannas, deserts, and temperate highlands. Second, we will uncover whether harsh climates promote peaceful cooperation by making conflict too risky, deploying cutting-edge artificial intelligence (AI) to dissect social networks in the wild. Third, we will test the core prediction that seasonal climates drive members of cooperative groups to adopt specialist roles, combining approaches to dissect molecular and morphological phenotypes (micro-CT-scanning, gene expression, and AI-driven morphometrics). Finally, we will examine which climatic conditions likely fostered the dawn of cooperation in the ancient ancestors of ants, bees, and wasps, developing advanced simulations and mathematical models. The vast geographic scope of this project, spanning nearly the entire African continent, will transform the field of social evolution. Our results will be of major interest for biologists studying cooperation, conflict, fitness, climatic gradients, and behavioural variation, as well as to social scientists, and provide a baseline for predicting how social insects will respond to climate change. Moreover, our AI deployment will benefit researchers in behaviour, ecology, and museum science. Our international team (UK, USA, Cameroon, Kenya, South Africa, Taiwan) will promote equitable benefit-sharing and capacity-building in Africa. Finally, we will provide outreach across continents, enthusing wide audiences about animal societies, extraordinary insects, and the potential for ‘big picture’ experiments to solve the fundamental outstanding riddles in biology.

UKRI Gateway to Research · FY 2025 · 2025-05

Synthesis plays a central role in accessing new chemical spaces to expand the frontiers of chemical discovery and invention. Through careful design and execution of chemical reactions, chemists can develop novel compounds that may not exist in nature or have never been synthesized. This process enables the creation of diverse functional materials (catalysts, pharmaceuticals, agrochemicals, polymers, and more) with unique properties and applications, paving the way for scientific advancements and technological breakthroughs. Within this field, alkenes are common motifs found in natural products, pharmaceuticals, agrochemicals and advanced materials, as well as acting as ideal building blocks in synthesis. They can have anywhere between 1-4 non-hydrogen substituents and can adopt either E or Z geometry. The nature of the substituents and the geometry of the alkene are key elements which determine the molecule’s properties. Whilst numerous methods exist for constructing alkenes with 1-3 non-hydrogen substituents, methods for constructing alkenes with four substituents are much more challenging since the alkene is more hindered, reducing reactivity and it is much harder to control geometry since the steric difference between substituents is much smaller when none of them are hydrogen. Indeed, classic olefination methodologies that are well-suited for di- and trisubstituted alkenes often fail when applied to the synthesis of tetrasubstituted alkenes. This project aims to address the challenges in the synthesis of tetrasubstituted alkenes by using reactions of tetracoordinate boron complexes with electrophiles. The tetracoordinate boron complexes are derived from simple, readily available, low cost building blocks . Following addition of an electrophile, molecular rearrangement occurs leading to a tetrasubstituted alkene with control of double bond geometry. This new method will lead to improved understanding of the chemistry of tetracoordinate boron complexes, and will provide a transformative approach for the stereoselective synthesis of tetrasubstituted alkenes from simple feedstocks.

UKRI Gateway to Research · FY 2025 · 2025-04

In the run up to the bicentennial of the abolition of the slave trade at the start of the twenty-first century, many in Europe and the US assumed there was a ‘we’ who agreed on the defining wrong of slavery, and the appropriate ways in which it can be represented in museums, heritage sites and other public spaces, and by whom. Today, those assumptions are publicly contested in multiple ways. Protest movements, including Rhodes Must Fall and Black Lives Matter, have foregrounded the arguments of critical race theorists concerning the foundational role of racial slavery in the development of the modern social and political order in Europe and the United States, and its continuing impacts. This has prompted a questioning of the ways in which the past of slavery and antislavery, and the continuing afterlives of slavery, are (and are not) publicly narrated, visualised and memorialised. In line with recent shifts in museum work towards centring audience authority and participatory practice, some curators have begun to respond by including in audience-led content creation communities that, in their specific national context, are most marginalised by these histories. However, the history of slavery was simultaneously global, national and local. It generated multiple and diverse injustices and divisions, and can hold different meanings in different contexts, even amongst those most marginalised by it. Moreover, its living legacies are not necessarily experienced in identical ways in global south and north, yet global south voices have been largely absent from debate on the presence of slavery’s undead past. Our mission is to include, amplify and differentiate marginalised voices from south and north in the process of researching, developing, testing and evaluating novel ways of curating the material culture and spaces of memory associated with transatlantic slavery. With its emphasis on inclusivity, diversity and equality, the Thrive model of team convening is ideally suited to research on how curators of museums and heritage sites can remember, narrate and represent the multiplicity and diversity of slavery’s past and afterlives, and develop ways to curate ‘against the grain’ of asymmetries in both north/south and racialised power. The project brings together a diverse team of curators, filmmakers, historians, anthropologists and sociologists from Britain, Brazil, Ghana and Dominica, to: map contestations around slavery at local, national and global levels; deploy pluriversal, collaborative, participatory methods with research participants from communities most marginalised by histories of slavery in those countries to develop and test inclusive methods of engaging multiple and diverse stakeholders; disrupt hierarchical top-down processes of meaning-making, and explore possibilities for forging reparative connections between places and people divided by histories of transatlantic slavery by bringing our research participants into dialogue with each other; with participants, co-create outputs in the form of content, film, and exhibitions that will afford a unique lens on global and local social justice. Slavery museums partners in Ghana, Brazil and Britain are redeveloping their exhibitions over the next three years, so the project will directly influence curatorial practice at three key points of the transatlantic triangle.