UNIVERSITY OF EDINBURGH

UKRI Gateway to Research · FY 2024 · 2024-08

The UK's Net Zero strategy is for all sectors of the economy to meet the Net Zero target by 2050. Similar long-term aims to move towards Net Zero emissions on the same timescales exist in other countries, including the USA. High-performance computing (HPC) is not exempt from needing to adapt to these strategic challenges, and pushing HPC towards sustainability and Net Zero is crucial if the scientific community is to keep justifying the use and cost of large-scale HPC resources in the face of climate change. Electricity consumption of data centres and systems is by far the largest contributor to the carbon footprint of operational HPC and minimising the energy that is consumed, and reducing/reusing waste, is therefore key in achieving Net Zero. The International Collaboration Towards Net Zero Computational Modelling and Simulation (CONTINENTS) project will build on the expertise of EPCC, the supercomputing centre at the University of Edinburgh, the National Centre for Atmospheric Science in the UK and the National Centre for Atmospheric Research in the USA to transform the state-of-the-art in sustainability and power/energy efficiency of computational modelling and simulation through an ambitious programme of research that will drive innovations in: data centre and HPC system operation; optimal use of hardware; machine learning applied to data analysis and numerical modelling; and software design and development strategies. As a specific use case, CONTINENTS will focus the application of its research on weather and climate modelling. These are both scientifically and computationally challenging, and compute resource intensive, domains that are vital to furthering our understanding of climate change and the factors that influence it. CONTINENTS is a unique interdisciplinary collaboration between leading centres of HPC research and service provision, atmospheric science experts, and numerical and machine learning application developers, providing a comprehensive approach to addressing the Net Zero challenge from the data centre all the way through to individual applications using both computational and climate science expertise. The projects objectives include: establishing a long-term collaboration between leading supercomputing researchers and centres in the UK and USA; pushing the boundaries of sustainable operation of data centres; exploring the use of novel and specialised hardware; developing new methods for performance, power and energy efficient software development and deployment; minimising the resources needed for moving, processing, analysing and storing data; and creating a collaborative research environment that encourages sharing of expertise and knowledge.

UKRI Gateway to Research · FY 2024 · 2024-08

This proposal concerns new strategies for the study of quantum field theory (QFT) in non-perturbative settings. There are complementary experimental and theoretical incentives for pushing QFT beyond standard perturbation theory around a trivial vacuum. Upcoming experiments will probe strong field effects from quantum electrodynamics to gravity, and proposals for extending the holographic principle to asymptotically flat spacetimes require detailed knowledge of QFT beyond Minkowski space. The fundamental quantity underlying these twin imperatives is the S-matrix: the operator encoding the scattering of asymptotic states. Unfortunately, the vast majority of techniques employed in modern approaches to the S-matrix break down as soon as strong background fields or spacetime curvature are introduced. A crucial exception to this is provided by twistor theory, a framework encoding physics in terms of complex geometry. My recent work has demonstrated that twistor theory can deliver precision frontier calculations in strong field QFT and is intimately connected with approaches to asymptotically flat holography. These breakthroughs open the door on new approaches to QFT in strong backgrounds and holography in asymptotically flat spacetimes, as well as pushing twistor theory itself in novel directions. The team will deliver state-of-the-art calculations for scattering amplitudes and physical observables (both classical and quantum) in strong gauge and gravitational backgrounds including plane waves, beams, instantons and black holes, directly linked to detection targets at current or upcoming experiments. We will provide detailed bottom-up data for holography in asymptotically flat spacetimes, as well as using conformal and holomorphic field theory methods to create top-down models for the boundary dual. In parallel, we will develop new applications for twistor theory in its own right, in higher-spin theories, higher-dimensions and algebraic geometry.

UKRI Gateway to Research · FY 2024 · 2024-08

Studies investigating the effects of nanoplastics (NPs) on aquatic organisms used concentrations between 2 to 7 order-of-magnitudes higher than those predicted in the open ocean. These studies divided the community between those sounding the alarm due to the observed ecotoxicological effects, and those predicting that NP concentrations in the environment are far below any threshold-effect. Most experiments were inadequately designed, and thus the results unsatisfying. Fit-to-purpose experimental designs have been hindered by a lack of appropriate NP models, analytical methods, and monitoring strategies for predicted NP concentrations. Using [14C]NPs and conventional nuclear techniques, I have recently modelled that scallops, chronically exposed (> 1 y) to environmentally realistic NP concentrations (15 .........g/L) might accumulate and reach NPs body burden where effects are observed by those sounding the alarm. Astonishingly, this suggests that NPs might already be beyond threshold-effects in organisms and harming the marine biota. Here, I propose an innovative approach that will overcome the analytical limitations to correlate potential local biological responses with mapping and quantification of NPs under realistic environmental settings. By developing [14C]NPs of the most produced plastics, and combining then with the analytical power of the accelerator mass spectrometry, ion beam analysis and mass spectrometry imaging, IMAGINE will answer whether NPs in the oceans are already beyond "threshold-effect" concentrations? This novel analytical approach will provide a unique insight into the potential effects of NPs following chronic exposures and will: 1) provide key intrinsically radiolabelled NP models; 2) develop an analytical suite to generate spatially-resolved toxicokinetic and metabolomic data; 3) perform chronic NPs exposures at predicted NPs concentrations; 4) answer whether key NPs accumulate and induce local biological responses at predicted concentration

UKRI Gateway to Research · FY 2024 · 2024-08

Regarding democratic processes, the academic world usually pays attention to Western-considered models and tends to ignore the value of other socio-cultural realities such as the Japanese. CINETIVITY aims to promote scholars' interest in and knowledge of the democratic process of post-war Japan as a universally relevant phenomenon by focusing on a key element in this historical experience: the debates that took place about how best to develop a form of political subjectivity or agency (shutaisei) in the people that would prevent individuals from being dragged into authoritarian regimes. Existing scholarship on the "shutaisei debates" assumes the written word as the primary medium of controversy overlooking other modes through which the debates took place. To address this gap in our understanding and to change the way scholars think about the phenomenon in question, this interdisciplinary project will investigate how filmmakers used the practice of cinema to intervene in the conception of shutaisei. CINETIVITY is expected to point out the value of the process whereby post-war Japanese intellectuals and filmmakers fostered democracy, thus inspiring the European civil society in an age like the present, when the memory of totalitarian regimes is gradually fading and authoritarian movements are gaining ground. The intersection between Political Philosophy and Film Studies which lies at the core of the project will bring a new perspective reinforcing the scientific community's knowledge on post-war Japanese democratic ideas and films while bridging the disciplinary divides that limit our ability to conceptualize political processes and aesthetic movements across multiple fields. Under the supervision of Dr Chris Perkins (Senior Lecturer in Japanese), the applicant will build upon his current skill set by receiving thorough training and mentoring, and will expand his international experience and professional networks at the University of Edinburgh.

UKRI Gateway to Research · FY 2024 · 2024-08

Context Flow mental states improve creativity, stress resilience and wellbeing, cognitive performance, productivity, engagement and mood (Csikszentmihalyi, 1990). We propose to commercialise a scaleable and accessible product, Zeitgeist, that trains Flow states through creative collaborative engagement activities. The Challenge A global Stanford study suggests 120,000 excess deaths a year through stress at the workplace (Pfeffer, 2018). Extensive literature links acute and chronic stress to ageing, cognitive function, and mental health (e.g., Marin et al., 2011). Stress treatment traditionally includes psychological treatments such as cognitive behavioural therapy, and drugs such as benzodiazepines and antidepressants. This project will develop a Flow-training product which may reduce or eliminate the use of these medications and overall improve stress resilience. We utilise creative collaboration and participation engagement methodologies within a digital scaleable product. To train Flow states, it incorporates digital innovation-based and creative cognition frameworks which have been shown to reduce cognitive decline and optimise cognition throughout adulthood (Chapman, 2016). Aims and objectives We will build a scaleable product to train Flow states and commercialise this within different mental health and productivity contexts. This builds from our previous AHRC-funded project which enabled us to develop a proof-of-concept which visualised pairs of participants' Flow states in real-time utilising AI-classification of brain activity data streamed from wearables. The visualisation was originally an art installation utilising holographic imagery, and this project will scale this up to a multi-device online visual application using AI-classification with data from easily accessible wearables such as smart watches which measure heart rate variability (HRV). This Minimum Viable Product (MVP) will be facilitated through an interactive online interface that embeds creative collaboration activities relevant to different workflows to actively enable Flow states. Potential applications and benefits Our original AHRC pilot studies showed heightened social connectedness, mood and active involvement when in Flow states, between pairs of participants situated locally with each other (Rahman, Gingrich & Hignell-Tully 2023). Now we will explore commercialisation feasibility for (1) healthcare professions and (2) creative professionals, wherein the MVP can be utilised within pairs of participants who are remote from each other. There will be applicability in other markets which will be explored in the longer term beyond these 6 months. Within healthcare, Zeitgeist is aimed at significantly enhancing interpersonal attunement skills, vital for patient care especially within mental health.A study by Marcussen et al. (2020) found improved mental health outcomes in mental health inpatients assigned to a unit undergoing inter-professional training. Excellent interpersonal skills lead to better patient adherence and satisfaction with treatment plans, which is crucial to patient care. This initiative aligns with NHS England's dedication to innovative healthcare training. Despite a strong reputation, UK creative industries are facing rapidly increasing competition in the global innovation race particularly from Europe and US.Post-Covid, 43% of UK workers are preferring hybrid-working and increasingly international global teams emphasise the need to collaborate efficiently and cohesively for peak creative performance. By enabling enhanced social connectedness and Flow, Zeitgeist will enable peak creative performance via an online remotely connected interface.

UKRI Gateway to Research · FY 2024 · 2024-08

Our global technological infrastructure depends on producing smaller, faster, and energy-efficient electronic devices. However, the miniaturisation needed to increase power density leads to larger heat fluxes, representing a bottleneck for next-generation electronics. Current thermal management systems (TMS) are both inadequate and inefficient, requiring vast natural resources. Novel, energy-efficient, and ultrahigh performance TMS are urgently needed in order to sustain economic growth while combating climate change. Nanomaterial-enhanced two-phase cooling has recently shown immense promise, but limitations in our understanding of nanoscale interfacial heat transfer - where the nanocoating or nanostructure meets the coolant liquid and where the liquid meets its vapour - in experiments has prevented this promise from being realised. The proposed work is of fundamental engineering science which will radically improving our understanding of interfacial heat transfer. This will be achieved by: i) combining molecular dynamics (MD) simulations and interfacial phonon analysis to develop new theoretical models for heat transfer across simple solid/liquid interfaces; ii) developing machine-learning-powered MD to extend this approach to realistic nanomaterials and coolant liquids; and iii) building a first-of-its-kind multiphysics simulation toolkit for TMS design, and validating against novel experiments in two case studies involving emerging nanomaterial-enhanced TMS: a) pool boiling using nanocoated surfaces; and b) evaporative cooling within nanoporous membranes. NANO-COOL will fill critical knowledge gaps and open an entirely new research field: "Simulation-driven design of nanomaterial-enhanced two-phase cooling for electronics". Results of NANO-COOL will be published as open-source models, open-access articles, and open data repositories. The long-term ambition of NANO-COOL is to become the enabling framework for novel two-phase TMS design.

UKRI Gateway to Research · FY 2024 · 2024-08

Despite substantial progress in the use of renewable energy, fossil fuel still accounts for 80% of global energy sources, which led to 34.9 gigatons of CO2 emissions in 2021. One feasible solution to this problem is the widespread deployment of CO2 capture facilities at large point sources, e.g., coal-fired power plants, which account for over 30% of global CO2 emissions. However, the availability of an economically affordable CO2 capture process is still a grand challenge as the conventional technologies suffer from huge energy requirement (3.5-4.0 Gigajoule per ton of CO2, GJ.tCO2-1) and large equipment size. CATNA-CO2 will respond to this global challenge by combining and developing two emerging technologies, nonaqueous absorbents and catalyst-aided solvent regeneration, to enable an energy-efficient CO2 capture from a typical combustion flue gas (12 v/v% CO2). A smart selection of diluent with a lower heat capacity than water will lower the energy consumption, while catalyst-mediated regeneration will optimize the CO2 desorption at a low temperature, further reducing the regeneration energy consumption. CATNA-CO2 will (i) develop inexpensive catalysts to enable a low-temperature CO2 capture process using a nonaqueous absorbent, and (ii) evaluate the catalytic regeneration process on a bench-scale unit with a focus on desorption kinetics, interfacial area, mass transfer coefficients, and regeneration heat duty. Moreover, synergistic benefits of nonaqueous absorbent and catalytic regeneration on the overall CO2 capture process will be evaluated to assess the reduction in equipment sizing. Solvent regeneration at a low temperature can enable efficient capture facilities to be installed at a wide range of industrial sites to achieve EU 2030 targets of at least 55% reduction in CO2 emissions.

UKRI Gateway to Research · FY 2024 · 2024-08

This proposal addresses a major need to increase understanding and improve treatment of a group of severe developmental diseases caused by activating mutations in the PIK3CA gene. These are collectively called the PIK3CA-related Overgrowth Spectrum (PROS), and they begin before birth. The PIK3CA gene controls cell and tissue growth, and when it is genetically activated, the rules that ensure orderly, co-ordinated tissue growth are broken. Unhealthy increased and disorganised growth ensues. Mutations are found in only some cells and tissues, a situation called genetic mosaicism, and this produces patchy, asymmetric excess growth. This often severely affects blood vessel formation to produce major risks of blood clots, bleeding and infections that can be life threatening, while other functions (e.g. breathing, walking) are also commonly affected by increased tissue bulk. PROS is incredibly variable despite the common underlying mechanism. Many affected patients wait years for specific diagnosis, if it is ever made, as PROS does not "belong" to any one medical or surgical speciality. When PIK3CA mutations were found to cause these diverse diseases, new opportunities to treat them emerged. This is because the same PIK3CA mutations causing PROS are common in cancers. Although PROS causes cancer very rarely indeed, PIK3CA-targeting drugs developed for cancer have raised great hopes in PROS, with one drug recently licenced in the USA based on an uncontrolled registry study. However while this has some benefits, these are partial, and side effects are frequent. Thus major need exists to improve medical treatment. In the rush to test cancer drugs in PROS, major questions about how PIK3CA mutations cause the disease have not yet been unanswered, although these may hold the key to developing new, smarter treatment. The scientific and clinical complexity of PROS means that ambitious multimodal translational research is required to advance understanding. In this project a team of two clinician scientists and three fundamental scientists will combine expertise in clinical medicine, genetics, stem cell biology, animal disease modelling and sophisticated data analysis. The proposal has been informed by working with a PROS patient advocacy group (clovessyndrome.org) that has funded key preliminary work. The project will use cutting edge single cell analysis of affected human tissue from PROS patients, combining this with the power of disease modelling in human pluripotent stem cells and zebrafish. Findings from human tissue and the model systems will be combined and used to identify new mechanisms driving PROS that might be targeted. Time windows when the existing clinical drug has its greatest effect will be identified, and by studying why sensitivity is greatest in these windows, we will devise and test new ways to increase the sensitivity of mutation bearing but not healthy cells. We envisage two potential new strategies: (1) to "trick" affected cells to enter a state more vulnerable to current inhibitors; and (2) to identify messages from affected cells that trigger healthy cells around them to grow too much. If these messages can be disrupted then this may produce a new line of attack to combat excess growth in PROS. Outcomes of the study will include 1) identification of new strategies worth testing as PROS treatments; 2) fundamental insights into the way tissue growth is regulated that are relevant also for cancer, and 3) key lessons about the best ways to study other "mosaic" genetic diseases.

UKRI Gateway to Research · FY 2024 · 2024-08

Crohn's Disease (CD) is a chronic inflammatory condition that can affect any part of the intestine and currently has no cure. It affects 6.8 million people worldwide with UK healthcare costs in excess of £1 billion per year. Recent data suggests that the despite significant progress in treatments over the last 2 decades to help control disease, upto half of patients still develop progressive bowel scarring that require surgery and upto 70% needing surgery within a 10 years from diagnosis. Unfortunately this is not a cure and some still require repeat surgery. These features have a devastating impact on an individual including education, work and social life. Preservation of a healthy length of small bowel that is free of disease is critical to prevent the long term risk of gut failure and death. Our current treatments focus on resolving inflammation but there are no treatments targeting scarring (fibrosis), its activity and its progression. A major hurdle in our progress towards anti-scarring treatments and advancing care in CD has been our inability to identify bowel scarring accurately using non-invasive tests; this being critical in developing new treatments that prevent permanent bowel damage. Although several tests are available to image the gut including computed tomography (CT), ultrasound and magnetic resonance imaging (MRI), there are no techniques to measure how active the scarring (fibrosis) process is over time. Current tests cannot predict scarring progression and eventual surgery in patients with CD. Therefore current management is 'reactive', dealing with complications that arise over time rather than 'proactive' aiming to prevent fibrosis and eventual surgery. Our limitations in diagnostics and disease related risk stratification has also limited our progress in developing anti-scarring therapies in this field. I am in a unique position to investigate a novel method that can identify scarring activity and track progressive bowel damage without the need for invasive tests. In this study I propose to use a 'dye', also known as fibrosis associated protein inhibitor (FAPI), that tracks scarring and its activity in the gut. The presence and amount of FAPI within an area of scarring can be detected using our current imaging tests (positron emission tomography and Magnetic resonance imaging: PET/MRI). Previous work from our partners have shown that this method can detect scarring within the heart, lungs and kidneys but this has not been studied in the intestine. If successful, this study will be the first method for detecting scarring activity in CD and have the potential to revolutionise care for this condition. Output from this work could facilitate new drug development to halt the processing of scarring (fibrosis) and improve the outcomes for patients with CD.

UKRI Gateway to Research · FY 2024 · 2024-07

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

UKRI Gateway to Research · FY 2024 · 2024-07

The primary objective of the project is to provide the United Kingdom with a unique, world-class research & training radioisotope infrastructure for environmental science. The general technique of radiolabelling involves labelling a molecule with radioactive atoms to follow the fate of that molecule within a specific cell, a particular tissue, an entire organism, or even an ecosystem (e.g. using mesocosms). Current use of radiotracer techniques in medicinal sciences has reduced the price of ultra-sensitive analytical equipment and made them accessible to other areas of knowledge such as biogeochemistry, ecotoxicology, environmental engineering as well as food security. It is important to note that radiolabelling approaches always uses very low doses of radiation so that the labelled molecules never pose any threat to the organisms under investigation or to the experimenter. Nevertheless, the envision facility is designed so that radioisotopes are never released into the environment. The project consists of setting up an Applied Radioisotope & Environmental Laboratory (ARIEL) for the safe handling of radioisotopes and their use as radiolabels in various type of samples such as sediments, soils, water, and organisms exposed to very low levels of radiations in environmentally realistic experimental settings. The laboratory will include (i) an experimental bench for organism exposures to radiotracers; (ii) a working space for syntheses of labelled molecules, sample preparations as well as space for chromatographic separation and cryo-microtomy; (iii) a dark analytical room with various radioisotope detectors (alpha, beta and gamma radiation) to perform the Quantitative Whole-body Autoradiography. We are proposing the expansion and refurbishing of the radiochemistry laboratory in the Department of Chemistry at the University of Surrey on a modest surface of no more than 30 m2. Currently, our radiotracer working group has only the exclusive use of a very small laboratory (ca. 12 m2) where we cannot house the NX 70 cryomicrotome (recently funded by CAMS # 600310/10 fellowship - Tracking Nanoplastic in Biological Tissue awarded to the present PI) and other equipment already in our possession (i.e. dedicated Glove box, in vivo gamma counter, liquid scintillation counter). This space could not house the necessary equipment for the long-term development of the radiotracer laboratory herein proposed. To complete the laboratory, we are proposing to acquire new equipment including an oxidizer, a liquid gamma counter, a super low-level liquid scintillation counter and a phosphor imager with lead shielding boxes. ARIEL will offer a unique opportunity world-wide to train highly qualified personnel via the Bachelor, master and doctoral programs in radiochemistry at the University of Surrey. The research that will be generated by the laboratory will be key in terms of acquiring new knowledge on the behaviour of aquatic species and ecosystems in the face of environmental stressors (e.g. toxic inputs and environmental change). As such, the project proposed aligns with the university strategic research theme of sustainability. The priority of the laboratory is to provide a full characterisation of the fate of plastic particles and other hazardous emerging contaminants in environmental matrices. The laboratory will provide a state-of-the-art facility for the next generation of ecotoxicology and environmental studies.

UKRI Gateway to Research · FY 2024 · 2024-07

RNA is a natural molecule that all organisms produce to instruct cells which proteins to make and also to regulate the amount of proteins that get made at different times and in different cells. There is increasing interest and capacity in designing RNAs to act as drugs to regulate protein expression in disease. Yet a major challenge is getting the RNA drugs delivered to the specific cells that need it, in a way that is safe and efficient. Our solution exploits the fact that some parasites have evolved their own RNA delivery systems in order to transfer their RNAs to mammalian cells and we have identified one natural RNA delivery protein that appears potent and simple to reconstitute. This is a novel nematode protein ("exWAGO") that nematodes release, in complex with RNA, which gets internalized by mouse intestinal epithelial cells (9, 10). Although first discovered in association with extracellular vesicles, we have data demonstrating that the recombinant protein itself gets taken up by mammalian cells and can be loaded with synthetic small RNAs (Fig. 1-2 below). Our aim here is to test the ability to design and load RNAs into the exWAGO protein to treat disease, with a focus on respiratory infections.

UKRI Gateway to Research · FY 2024 · 2024-07

The pressure of around one million atmospheres is an important milestone for systems composed of molecules. Pressures around this value are required to break the strong covalent bonds which hold molecules together and hence transform molecular systems into non-molecular systems. This change from molecular to non-molecular leads to profound changes in properties. Hydrogen has been reported to become a metal and this metallic form may be the cause of Jupiter's magnetic field. The hydrogen atoms in water and ice detach from the oxygen atoms and become mobile so that they conduct electricity in a way similar to the way that lithium ions in the batteries of laptops and phones conduct. Hydrogen sulphide forms a metallic compound which superconducts at a temperature of only -70 C. A study of these and similar phenomena yields information that is of both fundamental and technological importance. For example, the behaviour of hydrogen atoms provides stringent tests for our understanding of quantum behaviour, the way hydrogen-bonded solids like ice behave provides insight into the way biochemical processes work, and novel superconductors offer new routes to a potential room temperature superconductor which would transform power distribution medical imaging and could make a 'Back To The Future II' hoverboard a reality. However, our understanding of these and other important hydrogen-rich systems at million atmosphere pressures is limited by the fact that the most fundamental information -- the position of the hydrogen atoms in the crystal structures -- is currently not known. The reason for this lack of information is that neutron diffraction which is the only technique able to measure hydrogen atom positions directly was until recently restricted to pressures below 300,000 atmospheres and so information on the positions of the hydrogen atoms had to be obtained indirectly or from computational modelling. For the past seven years we have been developing the use of suitable technology for neutron diffraction studies using the SNAP instrument and the Spallation Neutron Source at Oak Ridge National Laboratory in the United States. We have now reached the stage where structures can be successfully determined at pressures in excess of one million atmospheres using both powder and single crystal diffraction techniques. This project aims to use a so called diamond anvil cell where the sample is compressed between two large gem quality diamonds to study the structures of hydrogen, ice and related ices (ammonia hemihydrate and hydrogen chloride), and very high Tc superconductors up to million atmosphere pressures.

UKRI Gateway to Research · FY 2024 · 2024-07

Glaciers and ice sheets have different temporal and dynamical responses to climate change. Consequently, in most glaciological studies, they are studied independently but their ice volume needs to be combined in global Sea Level Rise (SLR) assessments and projections. Antarctic Peripheral Glaciers and Ice Caps (APGs) make up the largest global glacier area outside the ice sheets (~132,867 km2) and are located around Antarctic islands. These ice bodies experience marked spatial variations in temperature, thus are particularly sensitive to short-term (decadal) changes in the ocean-climate system. There is ample evidence that since 1950, parts of Antarctica (where APGs are located) such as the Peninsula, West Antarctica and Marie Byrd Land, have experienced substantial changes in ocean and atmospheric temperatures, this suggests that all APGs could be significantly vulnerable and potentially contribute up to 143.89 mm of SLR should they disappear entirely. The reduction of APGs volume will result in the production of meltwater around Antarctica, which freshens the surface ocean and strengthens the stratification in regions where dense water is formed. The production of Antarctic meltwater can alter the abyssal ocean overturning, with implications for global ocean biogeochemistry and climate that could last for centuries. At the local scale, large inputs of turbid meltwater from tidewater glaciers can result in a strongly stratified, low-light coastal environment, characterised by higher temperatures and lower phytoplankton growth, which has further consequences for primary production. Despite the importance of knowing how much ice is stored in APGs that could potentially increase meltwater production and global mean sea levels, there is no agreement between regional modelling studies regarding of how much ice is stored in APGs. This disagreement arises from current glacier inventories not being able to distinguish APGs from the ice sheet and from errors produced by models when estimating APGs sea level rise potential (i.e. ice volume above floatation). APGs have either a clear separation, or some degree of ice dynamical connectivity with the ice sheet, which introduces ambiguity in how to sum APGs contribution to SLR. This ambiguity is addressed explicitly in SLR estimates for Greenland but not for Antarctica and has led to no regional and long-term estimates of APGs sensitivity to changes in the ice-sheet-ocean-climate system. This fellowship will fill critical knowledge gaps by estimating the probability of various levels of total SLR contributions and freshwater exports from APGs under different warming scenarios, producing informed ice volume and ice thickness distribution products, and a glacier mask for all APGs. These outputs will inform climate risk managers and policy makers as well as future Assessment Reports of the Intergovernmental Panel on Climate Change (IPCC), future experiments of the Ice Sheet Model Intercomparison Project (ISMIP) and Antarctic bed topography products. By combining remote sensing data and two state-of-the-art numerical frameworks, I will propose new standards and groundbreaking methods to simulate the response of APGs to changes in the ice-sheet-ocean-climate system, and assess which types of APGs are more sensitive to these changes. The outcomes of this fellowship will additionally benefit the large international community of glacier and ocean-biogeochemical modellers including ongoing projects that investigate ocean-glacier interactions in Antarctica and the Arctic. The software, data and tools developed will be open-source and fed into a well-established educational online platform, making the Antarctic cryosphere and these findings accessible to researchers, teachers and students worldwide.

UKRI Gateway to Research · FY 2024 · 2024-07

The Laser Ablation Capillary Absorption Spectrometry (LA-CAS) system enables low-cost stable carbon isotope analysis with near single cell spatial resolution. This is new capability for the UK. It provides a step-change in the detail and affordability with which we can study processes occurring in the narrow interaction zone between plant roots and soil (the rhizosphere), and has the capability to resolve a wide range of scientific questions. We have developed and utilise a range of methods to trace plant-derived carbon into soil carbon pools and microorganisms, to determine the impact of plants in shaping rhizosphere microbial communities and their functions. However, these approaches rely on bulk measures of carbon pools and fluxes which limits the mechanistic understanding of processes and biological traits that underpin the multiple interactions in the rhizosphere. The LA-CAS approach, by providing affordable high-resolution spatial data of isotope composition, allows us to examine impacts on individual organisms and individual processes. The LA-CAS system will be run as a small facility, with dedicated technical support. The intention is to start analysis for the current named consortium with research on plant-soil interactions, with the intention to open up this technology to a wide range of bioscience users; in theory for analysis of any biological sample. Initial focus is on (i) quantifying and locating resource exchanges in the rhizosphere for better understanding of the relationships between plants, microbial communities and their functions; (ii) determining the impact of plants on soil aggregation, and the processes regulating net carbon sequestration; and (iii) further enhancing analytical capability by combining LA-CAS and X-ray tomography imaging for relating root architectural traits and soil physical characteristics to the spatial location of deposited carbon. We will firstly test analysis on plant and soil material, taking forward the proof of concept developed in the US for rhizosphere soil. We will then undertake analysis on existing funded projects within our consortium, including for PhD students and early career researchers, as well as fostering new collaborations and funding applications via a LA-CAS user community. Samples (plant, root, soil) will be analysed from field and controlled environment experiments, in which plants (typically arable crops, or grass) are exposed to isotopically labelled carbon. For example, to establish the relative importance of genetically controlled traits such as root architecture, mycorrhizal colonisation and spatial patterns of root exudation on greenhouse gas emissions; and to quantify distinct C-stabilisation processes simultaneously through localisation of plant-derived carbon within the soil matrix. This data not only provides fundamental insight into how plant-soil systems work, but can, for example, be used to select next generation crops for resource use efficiency and capacity to improve soil health. Such approaches enabled by the LA-CAS analytical capability are critical to help address the complex interactions of some of the most intractable biological systems. This is fundamental to advance our understanding of living systems and we anticipate will lead to new bioscience-based solutions to key challenges, such as climate change, and food and nutrition security.

UKRI Gateway to Research · FY 2024 · 2024-07

The mental health platform will advance the UK Research and Innovation 'securing better health, ageing and wellbeing' strategic priority, across all UKRI research councils, for mental health. The platform will draw on expertise from multiple disciplines, including biological, social, computational and medical sciences, to address key challenges needed to advance our understanding of severe mental health and illness and inform more effective diagnosis, intervention and prevention. These challenges include heterogeneity within (and overlap across) diagnoses, poor mechanistic understanding of mental disorders, variability in measures used and a lack of objective biomarkers and a lack of diversity in consented research studies The platform will accelerate understanding of the mechanisms and determinants of severe mental illness to identify early and best treatments, interventions and support. Cross cutting threads throughout the platform include: 1. data sharing and open science 2. in-depth understanding of those who experience severe mental illness 3. research into new markers and targets for intervention 4. exploratory studies in humans 5. harness, and enhance, the UK's rich data sources to tackle mental health research challenges 6. provide a basis for expanding capacity, partnerships and stakeholder engagement 7. focus research to tackle inequalities and benefit populations most in need The mental health platform includes a network of investments comprising 5 mental health platform challenge-led hubs, the DATAMIND Mental Health Data Research UK Hub, a coordination centre led by a director, and activities supported through a collaboration and innovation fund to promote and incentivise collaboration across the hubs and with external partners. Future funding will be support early career researchers through fellowships through a separate competition that will also drive networking across the platform. The coordination centre will be formed of the director and leadership team and will work closely with the leads of each of the mental health platform hubs. The director will assemble a team, which will include a project manager, communications and strategic engagement and administrative support.

UKRI Gateway to Research · FY 2024 · 2024-07

Lung cancer is the leading cause of cancer related deaths worldwide. Unfortunately, current methods like CT scans have limitations in detecting lung cancer early and evaluating treatment response promptly, causing delays in diagnosis/therapy. To address this, I will investigate the potential of a technology called fluorescent lifetime imaging (FLIM). FLIM can detect emitted light from cells in the body, and I have shown that the light emitted from cells within a cancer differs from that of non-cancerous cells. Although the reason for this discrepancy is unknown, my findings suggest a correlation with how cells regulate their metabolism, through a chemical called adenosine. The FLIM technology is state-of-the-art and designed for use during bronchoscopy (where a camera is inserted into the lungs to examine suspected cancers). Here, using specialised fibres that can reach lesions/tumours we can obtain real-time metabolic profiles of the cancerous tissue, enabling immediate cancer diagnosis. I will also use small chemical compounds that detect the overactivity of two cell types crucial in the response to treatments: fibroblasts and T cells. This approach may provide early indications of treatment effectiveness, such as chemotherapy, before changes are visible on CT scans. Aims: 1) Define FLIM signals in lung cancer at both the cellular and whole cancer levels. 2) To investigate the relationship between FLIM signals and the activity of the adenosine pathway in lung cancer, linked to drug treatments. Objectives: Objective 1. Determine the cell specific FLIM signal in lung cancer and relate this to both the cells level of activation and function. Using surgically resected cancers, I will breakdown these into their individual cell component and measure the cell specific FLIM signal in each cell type. Parallel confirmatory experiments will tell us the cell activation and function levels. Then, using advanced culture methods that mimic cancer conditions I will understand what changes occur with drug treatments as we would use in the clinic, and relate this to how efficiently the cancer cells are killed. Finally, using an established large pathology set of lung cancers, I will make a unique atlas of all the cell types in cancer and their FLIM signal. This will be made into a shared community resource for other researchers. Objective 2. I will use a small device to allow us to understand how multiple combinations of drugs work in lung cancer, linked to FLIM. Using a device capable of delivering 20 drug combinations to small, confined areas of the cancer (less than 1 mm distance), I will study multiple combinations of drugs that target the adenosine pathway in lung cancer patients who have had their cancer removed. Using multiple laboratory techniques, including FLIM, I will measure how well the drug combinations have performed. The optimal combinations will be delivered (without the device) to patients a few days before their surgery for confirmation. Ultimately, we will aim to do the whole device experiments in patients' cancers before surgery, but this will be done with further research funding and on completion of the above stages of research. Objective 3. Assess FLIM signals in patients and combine this with small chemical compounds that report activity of fibroblasts and T cells. I will use an existing trial infrastructure in Edinburgh and will recruit patients with i) suspected cancer, ii) undergoing surgery, iii) planned for drug-based cancer treatment. Each group will have FLIM imaging combined with the chemical probes that can identify activated fibroblasts and signatures of cell death caused by T cells. This will gain valuable insights into the behaviour of the cancer and its response to therapy by FLIM. Together, this will determine if FLIM can be used as a tool for immediate diagnosis and early assessment of treatment response in lung cancer, ultimately enhancing outcomes for patients.

UKRI Gateway to Research · FY 2024 · 2024-07

Biomass, as the sole carbon-containing renewable energy source, will undoubtedly continue to play an indispensable role for Europe and the world in addressing the pressing challenges of energy crisis, climate change and environmental degradation. Converting biomass into biomass-derived carbon materials (BCMs) represents a crucial and unique approach to tackling these issues. As there remains a notable gap in our understanding of the mechanisms governing the multiscale structural evolution from biomass to BCMs especially under extreme conditions, TSBCM aims at achieving the targeted synthesis of BCMs by implementing three closely interconnected technical work packages, which are systematically comprehending the intrinsic mechanisms driving multiscale structure evolution using both conventional and unconventional methods (microwave and Joule heating) under extreme conditions, developing universally applicable methods to guide the preparation of BCMs towards desired structures, and demonstrating the proposed general methods through proof-of-concept applications of electromagnetic interference (EMI) shielding and energy storage sodium-ion battery (SIB). The University of Edinburgh (UEDIN) and its UK Biochar Research Centre (UKBRC) stand at the forefront of biomass conversion and utilization research. The applicant, beyond the expected excellent research, profits greatly from the experiences of international view and professional skills training (UEDIN, UKBRC, host) supporting his strive for an independent academic career as professor. The successful implementation of TSBCM will facilitate the commercialization of BCMs and accelerate their applications in broad fields of energy storage, EMI shielding, carbon reduction, electronics, etc. Naturally, the applicant, the host, and UEDIN are fully committed to the planned action and to a most successful outcome, which will in turn strengthen EU's world-leading position in renewable energy technologies.

UKRI Gateway to Research · FY 2024 · 2024-07

Hormones are crucial signalling messengers in humans and other organisms, including mammals, birds and fish. They travel in the blood to organs (e.g., liver, fat, ovaries, testes, brain) to control vital day-to-day processes such as reproduction and feeding, and also enable swift responses in response to stress e.g., fear, starvation, cold. Within organs, there are suites of cell types, all with different functions. Each cell has mechanisms to fine tune the amount of hormone acting e.g., pumps drawing in or removing hormones, proteins acting as storage tanks to hold reserve hormones or enzymes changing hormones between active and inactive states. Bio-scientists must measure hormones in these tiny pools to fully understand interlinked pathways forming the basis of health. With technology improving, even measurement in individual cells is coming into reach. Here we invest in a next-generation "liquid chromatograph triple quadrupole mass spectrometer" allowing us to measure hormones (and other small molecules) at previously unreachable levels of sensitivity and precision and indeed outperforming our existing instrument ten fold. Crucially, with greater sensitivity, this new instrument will allow measurement of hormones in smaller sized samples e.g., neonatal hair, exhaled breath and in small animals. Our team comprises research technical professionals (RTPs) and basic and clinical academic researchers working collaboratively. Our RTPs are experts in creating new, reliable approaches to maximally benefit from technology innovations and will develop ways to measure hormones in substantially lower levels than before. This will allow us to find hormones previously too low to measure e.g., aldosterone that controls blood pressure, sex hormones in ageing. Our RTPs will ensure high quality methods and robust dataflows to minimise human error, reporting to Good Clinical Practice, a high regulatory standard. Through team science, our basic scientists and clinicians will drive forward novel projects studying, e.g., neonates to understand stress and nutrition in pregnancy; animal models of metabolic health, from mice lacking proteins to pump or store reserve hormones to non-invasive free-living measures through hair and saliva sampling in large animal models; reproduction of managed and wild animals (e.g., birds, fish, horses) linking environmental stimuli to reproduction (nesting behaviour, water temperature); and mammalian models to unpick interactions between heat-generating fat (brown), body weight and environmental temperature. Thus with this new sensitive instrument we will implement new methodologies requiring extremely sensitive analytical technology to enable hormone analysis and open doors to previous unattainable scientific insights. In due course we will support wider bioscience in Edinburgh (e.g., neuroscience) and beyond (metabolic health), including working with industry. We will train and mentor our RTPs in advanced skills, and support and educate the next generation of bio-scientists. We have designed a robust programme to install and maintain the new system and built a business plan to ensure effective management moving forward within a specialist technology hub.

UKRI Gateway to Research · FY 2024 · 2024-07

Our proposal aims to develop a novel transformative approach to retrieve the mechanical properties of cells and their microenvironment with quantitative phase imaging (QPI): QPI Elastograpy (QPIE). These new capabilities are important since the mechanical properties of mammalian cells and the microenvironment, including extra-cellular matrix (ECM) play a pivotal role in diverse biological processes and disease progression with direct implications in development, healthy living and ageing. Despite its significance, a wider consideration of mechanical properties in biology is strongly limited by current barriers associated with state-of-the-art technologies such as the technical complexity of the equipment, the need for expert knowledge outside biology, or the requirement for cell manipulation preventing in situ measurements. QPI Elastography (QPIE) will be transformative for the biology work flow as it will provide elasticity data alongside phase contrast, DIC and fluorescence microscopy in a seamless fashion. To this end, we will deploy a unique approach integrating optics, physics, and computational methods enabling elasticity measurements with high sensitivity and accuracy at cellular resolution. In addition, our contactless method will generate new knowledge by allowing measurements of 3D samples. First, we will optimize our QPIE algorithms with the help of simulation, and gain insights in experimental procedure optimisation. Next, we will fully validate QPIE on micrometre size optical phantom of well-defined mechanical properties in the range typically found for soft tissues. We will then explore the biophysical cell behaviour in 3D microenvironment, with an isogenic HEK293 cells engineered to express or not the YAP/TAZ transcriptional mediators of the Hippo pathway. Finally we will push the limit of our method to study nucleus plasticity by leveraging QPI tomography together with QPIE.

UKRI Gateway to Research · FY 2024 · 2024-07

Each cell in our body contains thousands of molecular machines which are called proteins. Proteins execute dedicated functions in the cells. The information on the coding of such proteins is retained in the form of a long quaternary code in the nuclei of each cell as deoxyribonucleic acid (DNA). Each cell will have proteins dedicated to repair the damage caused by environmental stress to DNA, proteins dedicated to allowing cells to multiply their DNA copy and many other functions. The abundance of each protein in the cell must be carefully regulated to sustain cell survival and the integrity of the information contained in the DNA. Cancer cells have, typically altered protein abundance contributing to their increased proliferation states. The D'Angiolella laboratory studies the mechanisms underlying protein homeostasis in the cells and focuses on how these mechanisms are altered in cancer and contribute to cancer development. The understanding of these processes will help develop treatments to specifically kill the cancer cells leaving the normal tissue intact. The laboratory used genetic screens to identify the mechanisms of protein homeostasis at the basis of the repair of damaged DNA after treatment with radiation therapy. In the current proposal, the laboratory proposes to investigate in detail the mechanisms highlighted by genetic screens. Specifically, the study will focus on two proteins which control how the DNA is cleaved in the cells after radiation treatment to execute error prone or error-free mechanisms of DNA repair. The balance between these mechanisms is crucial to allow cells to survive in the presence of many DNA damaging lesions induced by radiotherapy. Altering these mechanisms in cancer cells could favour cell death and inflammation, eliciting an anti-cancer response. Thus, our studies will clarify the contribution of protein homeostasis in preservation of the genome integrity of any cell and, at the same time, reveal potential targets to exploit for cancer therapy.

UKRI Gateway to Research · FY 2024 · 2024-06

Infectious diseases profoundly affect the productivity and welfare of farmed animals and threaten sustainable agriculture and global food security. Moreover, zoonoses that transmit to humans from farmed animals exert high societal and economic costs and have pandemic potential. These challenges intersect with many of the most urgent issues of our era, including the rise of antimicrobial resistance and impacts of animal agriculture on the climate and environment. Moreover, control of animal and zoonotic diseases is becoming more challenging as pathogens evolve to escape vaccine-mediated immunity and drugs become less effective. This proposal brings together two BBSRC-sponsored Institutes that offer national capability to combat animal and zoonotic diseases. We offer unique infrastructure, expertise and resources and have deep connections across the research and innovation system. Our organisations are globally important in training the next generation of scientists, technical specialists and research professionals needed to tackle animal and zoonotic infections. In doing so, we address skills and capacities defined by UKRI as vulnerable. We will harness this position to catalyse knowledge exchange and collaboration, both across sectors and disciplines. In particular, we will use our extensive network of collaborations with businesses (particularly animal pharmaceutical and breeding companies) and public or third sector organisations to enhance porosity and develop staff of diverse types and career stages, including those who support research (e.g. in business development, legal advice, animal use, biosafety, facility management, etc) Research strengths our organisations include, but are not limited to: World-class fundamental research on host-pathogen interactions to design new or improved solutions for disease control. Development & evaluation of veterinary vaccines (supported by our joint Immunological Toolbox & International Veterinary Vaccinology Network). Innovation in vaccine manufacture & platform technologies (e.g. Centre for Veterinary Vaccine Innovation & Manufacturing at Pirbright). Selective breeding of animals with enhanced resistance or resilience to infectious diseases in partnership with breeding companies. Engineering Biology to confer resistance to infectious diseases (e.g. via genome editing or transgenesis). Development of alternatives to antibiotics. Development of specific & sensitive diagnostic tests for rapid detection of pathogens & drug resistances. Novel 3Rs approaches to study infectious diseases. Tracing the evolution & spread of novel pathogens & modelling the impact of interventions. Use of Artificial Intelligence to predict the tropism & risk of emerging pathogens. Our extensive partnerships with businesses provide a key route to implement advances at global scale. Moreover, we partner with public and third sector organisations in low- and middle-income countries to deliver gains for smallholder farmers to alleviate poverty and malnutrition (e.g. in collaboration with the International Livestock Research Institute).

UKRI Gateway to Research · FY 2024 · 2024-06

The objective of this project is to develop a standalone trusted execution module that enables secure cloud quantum computing. This module will undergo validation within the project by demonstrating a full stack software-hardware integration of the world's first secure optical access to a photonic quantum computing implementation for multi-user quantum cloud applications. Over the next three years, the consortium will conduct a (1) study, (2) development, (3) testing, (4) validation, and (5) demonstration of the HSM-QCC concept to obscure the computational task of the cloud computer. This project builds on a decade of research and development in several complementary domains, including hardware security, Quantum Cloud Computing, Photonic experiment, and software compilation. The original theoretical idea of a trusted execution environment in the quantum setting, namely QEnclave, was proposed by the members of the consortium which demonstrated that scrambling input states by single-qubit rotations in a trusted environment is sufficient to secure any universal quantum computing. However, the implementation of this core idea requires the multidisciplinary complementary expertise of this consortium to ensure all pieces can be assembled together to demonstrate and validate the vision. The target trusted environment will be a modified Hardware Security Module (HSM) with single-qubit quantum rotation functionalities, co-located with a scalable quantum cloud platform. A remote user, utilizing a classical cryptographic link to a quantum cloud platform, can securely obfuscate its desired quantum computation. The scrambling of the state will be performed according to the principle of Universal Blind Quantum Computing inside the HSM. To achieve this goal, the consortium will employ a general-purpose compiler that maps the target quantum algorithm of a user to an interactive client-server protocol and tailor it for our secure module.

UKRI Gateway to Research · FY 2024 · 2024-06

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

UKRI Gateway to Research · FY 2024 · 2024-06

Every year, approximately 5,700 people in Scotland experience three severe disadvantages at the same time: homelessness, drug addiction, and criminal offending. Most people facing these Severe and Multiple Disadvantages (PSMD) have suffered trauma during childhood, report lower quality of life and have poor health outcomes. They repeatedly offend, and die on average 30 years earlier than people living in mainstream society. Glasgow, Edinburgh, North Ayrshire and Dundee have the highest numbers of PSMD and drug death rates in the UK and Europe. An important barrier to improving outcomes is that PSMD struggle to access services. PSMD experience multiple problems like unmet health conditions, unsafe accommodation and lack of supportive relationships, preventing purposeful community connections. Their problems are rarely adequately dealt with by different services. Unmet health and social care needs increase the risk of overdose, emergency service use, and offending behaviour. The costs of caring for PSMD are 4-5 times higher than for people in mainstream society (due to criminal justice and emergency health care utilisation). Third sector (Charity) homelessness organisations tend to be trusted by, and accessible to PSMD, especially when going to where PSMD are (i.e. providing outreach). They offer help with accommodation, and vocational opportunities. However, many treatable opportunities are missed because healthcare professionals rarely go on outreach with them. If NHS clinicians were to join workers from charitable homeless organisations (many of whom have experienced SMD) to visit PSMD, the combination could help address many of the multiple health and social care problems experienced by PSMD. Such a collaboration (which we have called PHOENIx: Pharmacy/nurse Homeless Outreach Engagement Non-medical Independent prescribing) could potentially treat PSMD holistically on outreach. They could treat physical and mental health conditions, and drug addiction. They could also address welfare benefits, housing and encourage pathways to contribute to their communities. PHOENIx could improve health and, reduce reliance on crisis-focussed services, while reducing offending behaviours. This could address the social and economic disadvantages experienced by PSMD. Improving these outcomes is a UK homelessness research priority. In a successful small-scale study, PHOENIx appeared to delay time to non-fatal overdoses, Accident and Emergency visits, and hospitalisations. It appeared to improve quality of life and community connections. PSMD highly valued the PHOENIx intervention. Larger scale research is necessary to prove whether PHOENIx really does make a difference. Aiming to identify a solution that promotes economic and social prosperity for PSMD, our study will be set in Glasgow, Edinburgh, North Ayrshire and Dundee. We will randomly assign (like tossing a coin) 372 participants to either: (1) Usual care; or (2) PHOENIx in addition to usual care. PHOENIx participants will receive additional weekly visits from prescriber clinicians and third sector workers, for nine months. We will find out whether PHOENIx reduces the risk of fatal and non-fatal overdose, improves health, and community connectedness for PSMD. We will also find out whether it reduces Accident and Emergency visits, hospitalisations, criminal activity. We will look at what aspects may help or hinders delivery and rollout of PHOENIx across the UK, and whether it is value for money. If the study results are positive, we will use these results to drive a policy and practice change to improve the way we care for PSMD. This will make a big difference to PSMD, health services, social care, criminal justice systems and communities.