UNIVERSITY OF EDINBURGH

UKRI Gateway to Research · FY 2024 · 2024-11

Electronic cigarettes (‘vapes’) are an effective smoking cessation tool. However, the rise of disposal (single use) vapes among young people is an urgent public health priority. In 2021 disposable vapes were reported as the most popular type of vaping device by 7.7% of 11 to 17 year olds, by 2023 this figure had increased to 69%. Vaping in young people raises several health concerns, with the long-term effects unclear. One of the primary issues is the potential for nicotine addiction. Many e-cigarettes contain nicotine, which is highly addictive and could affect the developing brains of adolescents with continued use. Vaping has also been associated with respiratory problems, such as coughing, wheezing, and lung inflammation and may exacerbate asthma and bronchitis. Schools remain a popular setting for delivery of health interventions to prevent risk taking behaviour. While there are some existing school-based initiatives focussing on adolescents’ perceptions and behaviour around EC, at present, there is no evidence-based vaping prevention interventions targeting young people in secondary schools in the UK. Considering this gap, combined with the rising normalisation of vaping in young people, the proposed development study is both timely and essential to address a rapidly growing public health concern. The aim of the proposed study is to conduct the development work required to co-create a vaping prevention programme in the secondary school setting. This aim will be addressed via three research objectives: 1) to map and critically assess the applicability of existing vaping prevention interventions internationally for the secondary school setting; 2) to speak to a range of stakeholders to identify the key messages that young people need to be made aware of to delay or prevent them from vaping and; 3) to co-create a vaping prevention programme that combines tobacco prevention for secondary school settings. In addressing these research objectives, the proposed study will undertake a mixed-method research design comprised of three work packages (WP). WP1: literature review; WP2: consultation with key stakeholders and; WP3: programme theory development. The end product from this study will be a co-created, evidence based vaping prevention programme to be delivered in the secondary schools setting. This, in addition to the knowledge generated from the planned work packages, will have direct and indirect benefits across multiple stakeholder groups. Young people, school staff and families will benefit from an increased awareness of vaping harm and will have an opportunity to co-create programme theory. Young people will also be empowered to make informed decisions about their health, and potentially reduce nicotine harm by delaying/preventing vaping experimentation. Should the pre-set outcomes for this proposed development study be met, NHS Tayside have agreed to lead delivery of a feasibility study to test and refine our programme theory. Findings from this feasibility study will give a solid foundation to apply for future funding to conduct a pilot cluster randomized control trial.

UKRI Gateway to Research · FY 2024 · 2024-11

Almost every massive galaxy has a supermassive black hole in its centre, which grew from a small black hole as the Universe evolved. Such supermassive black holes do not only reside in galaxies, they are thought to significantly shape the evolution of their host galaxy and be one of the physical drivers behind the wide variety of galaxy shapes and sizes we see in the Universe today. There is no known way to directly form a supermassive black hole at the masses they have today. Instead, supermassive black holes started their journey as much lighter black holes when the Universe was young. Such light black holes, which then grew into supermassive black holes, are called "seed black holes". Seed black holes grew in mass through material that fell into the black hole, or through mergers with other black holes. To understand the tight link between galaxies and the supermassive black holes that we see today, we need to understand when and how seed black holes first formed and found their way into the centre of the galaxies in which we see supermassive black holes today. It was long thought that each galaxy would easily acquire one such seed black hole when the galaxy was young but recent work has shown that the process is not trivial. Black holes in the early Universe often form far from the kind of galaxies where we see supermassive black holes today, or are very light when formed and easily ejected from galaxies, and the timescales for them to settle (back) into the centres of galaxies can be very long. We do not yet have a good understanding of how seed black holes travel from their formation sites to galaxies, and whether they are able to remain in galaxies long enough to grow supermassive or whether they often get ejected again. In this project, I will tackle the difficult challenge of how black holes in the early Universe move in and around galaxies, to understand when and how they first found their way into the galaxies where we see supermassive black holes today. To do so, I will combine powerful simulations with recent observations of the early Universe to study how a diverse population of black holes evolves in and around early galaxies. In this way, I will pave the way towards understanding how galaxies first acquired their seed black holes, and when the coevolution between black holes and galaxies began.

UKRI Gateway to Research · FY 2024 · 2024-10

Ethiopia is a low-income economy with a population of around 120 million people, about 34% of whom are adolescents.  Research has found that around one in five Ethiopian adolescents has stunting and one in ten are obese, demonstrating a double burden of malnutrition.  Poor nutritional health is contributing to the high level of communicable, maternal and neonatal morbidity and mortality in Ethiopia. Alongside economic drivers of nutritional health, social and cultural drivers are recognised including rural to urban migration. Access to high school education is limited in most rural areas of Ethiopia, meaning that adolescents often relocate from their rural villages to typically unfamiliar urban areas to continue their high school education, where they will be away from their family.  The adolescents may experience vulnerable financial and housing situations, increased access to unhealthy foods and alcohol and reduced access to spaces for physical activity.  This has been identified as critical point at which intervention is needed to support healthy behaviours and subsequent health and wellbeing.  The aim of this project is to co-develop with young people and other stakeholders in Ethiopia a systems-embedded intervention to support adolescent nutrition and related health-behaviours around the transition to independence.  This aim will be achieved through the following objectives: Engage with diverse young people and other stakeholders in two cities in Ethiopia. Use participatory systems mapping tools and techniques to understand and document the systems relevant to the intervention and identify key points where change might be achieved (acknowledging external factors and assumptions). Identify mechanisms most likely to trigger the identified changes and develop these into a programme theory with participants to ensure the intervention is feasible, ethical and acceptable. Cross-comparison between the two cities throughout to ensure that relevant insights are not missed, and context-dependent and core aspects of the intervention are identified. Refine the intervention and engage nationally to establish the potential to transfer the intervention into different settings. The project team includes academics and practitioners from the UK and Ethiopia with experience in complex health intervention development, systems methods, adolescent health and nutrition.  Working in the Ethiopian cities of Jimma and Bule Hora, the project will combine established intervention development and systems thinking practices to meet the objectives.  We will work with young people who have migrated from rural to urban areas in Ethiopia for their education, as well as stakeholders such as parents, community representatives, health offices, educational organisations and charities to co-produce a feasible and acceptable intervention that is most likely to be effective.  This will involve initially co-producing systems maps to identify aspects of the system that are modifiable in each city.  Subsequently, literature review and further co-production will be combined to develop programme theory for an intervention. We will develop capacity in both Ethiopia and the UK in systems thinking, participatory systems mapping and intervention development.  Through the application of these approaches the intervention will be adapted to the complexity of the context.  By working in parallel in two cities, we hope to gain insights about the core and context dependent aspects of the intervention, seeking to document the intervention in terms of processes and relationships to support scale across to other settings.

UKRI Gateway to Research · FY 2024 · 2024-10

Plants transport sugars around their bodies in the specialised tissue termed the phloem. The phloem is essential for plant life and underpins the growth and survival of all economically important plants, whether crop or forest species. Given how important the phloem is for plant life it might be predicted that we would have a good understanding of its evolution. However, despite the vital role the phloem plays in living species our understanding of phloem evolution is rudimentary. Key questions remain unanswered including: (i) when did the phloem originate, (ii) how has its structure, function and genetic toolkit evolved over the past 400 million years, (iii) how has phloem evolution been driven by climate change? In this project we are answering these major questions and fundamentally increasing our understanding of phloem evolution over geological time. To achieve this we are working on three specific objectives: 1. Defining the origin of the phloem in land plants 2. Revealing major evolutionary innovations in phloem structure and function in relation to climatic change through geological time. 3. Characterising the genetic innovations that underpinned the diversification of the phloem In the initial stage of the Future Leaders Fellowship we have made substantial progress to achieving these objectives and are poised to make new discoveries that will change our understanding of phloem evolution. In the renewal phase of the Fellowship we will continue on our path to achieve these objectives and answer the overarching questions about phloem evolution. We will greatly expand on our objective to characterise the genetic innovations that underpinned the diversification of the phloem, with a broad scale approach to characterise the expression of genes involved in phloem development in ferns and lycophytes and aim to discover novel regulators of the phloem development in lycophytes. Collectively the outcome of the project will make a step change in our understanding of phloem evolution over the last 400 million year and demonstrate the added benefit of taking an interdisciplinary approach, combining studies of living plants, fossils and genetic networks together to answer major questions in plant evolution.

UKRI Gateway to Research · FY 2024 · 2024-10

During pregnancy, there are dramatic changes within a women's cardiovascular system (heart and blood vessels), including a large increase in her total blood volume and redistribution of blood flow to various organs. This helps to increase the amount of blood supplying the placenta, the structure which provides oxygen and nutrients to the baby via the umbilical cord. Sometimes this process can go awry, resulting in problems for mothers such as dangerously high blood pressure and organ damage (pre-eclampsia). Babies who do not receive sufficient oxygen and nutrition through the placenta are at risk of not growing at a healthy rate (fetal growth restriction), or even of dying inside the womb (stillbirth). Pre-eclampsia and fetal growth restriction are common reasons for babies needing to be born early, which can increase their chances of both short and long-term health problems. Taking aspirin during pregnancy can help to improve the blood supply to the placenta in women at increased risk of these conditions. However, once pre-eclampsia or fetal growth restriction develop, the only "treatment" is for the baby to be born. Currently, we do not have reliable methods for identifying women who are most likely to develop poor placental blood supply, and it is difficult to detect problems until they are causing dangerous issues for mother or baby. In recent years, there have been great advances in the ability of scientists to develop "digital twins". These are computational models which combine large amounts of data about an individual to create a virtual replica of biological systems and processes within that person. During this project, I plan to collect detailed measurements from pregnant women and use these to develop personalised "digital twins" of the cardiovascular system. This will allow me to study how the blood supply to the placenta, and the distribution of blood flow throughout the body, change during pregnancy for individual participants. Women will be recruited to this study from the general population and from a specialist antenatal clinic for women affected by problems with how the placenta is functioning. I am particularly interested in investigating how blood flow to the vessels in the retina (a structure in the back of the eye) changes at different stages of pregnancy. It is possible to take detailed pictures of the blood vessels in the retina using specialised cameras; I aim to find out whether such pictures can provide information about how a women's entire cardiovascular system (and ability to nourish her baby through the placenta) is coping with pregnancy. This project will lead to improved understanding of what goes wrong when the placenta does not develop an adequate blood supply. My research will also allow me to develop methods to detect subtle signs of an issue, for example by picking up signals from retinal vessels and in the rest of the circulation, before the development of dangerous complications for mother or baby. Being able to more accurately identify individuals at risk of poor placental blood supply will allow midwives and doctors to monitor pregnancies appropriately, target interventions like aspirin more effectively, and deliver babies at the safest time. This will help to reduce the harms to mothers of becoming unwell with pre-eclampsia, and the dangers for babies of being born too early or too small.

UKRI Gateway to Research · FY 2024 · 2024-09

One of the greatest scientific events of the century is the discovery of the Higgs boson by CERN's Large Hadron Collider (LHC). Yet the LHCs discovery potential has by no means been exhausted as collisions are now happening with an increasing rate at energies never achieved before by mankind. With more and more data being accumulated over the next 15 years we will obtain measurements at unprecedented levels of precision. This data will put stringent new tests on the Standard Model (SM) of particle physics. While the success of the SM is the greatest achievement of particle physics to date, it also poses many mysteries to physicists. For instance, the SM does not explain the observed matter-antimatter asymmetry, or the nature of dark matter and dark energy in the universe. To overcome these problems new models, featuring as exotic ideas as supersymmetry or extra dimensions, have been proposed. So far none of these models could be detected in experiments, but beyond-the-SM (BSM) physics may still be detected at the energy currently explored by the LHC. To distinguish new physics from the SM, theoretical calculations must match the accuracy of the experimental measurements. This poses a tremendous challenge since it is impossible to calculate general observables exactly in quantum field theory. Instead, theoretical physicists resort to what is called the perturbative expansion; this is a systematic way to expand the complicated functions, which describe the scattering rates, in a series in the interaction strength, where each successive term is smaller than the preceding. By calculating enough terms in this expansion one can thus obtain increasingly reliable results. Especially in quantum chromodynamics (QCD), which governs the dynamics of the constituent quarks and gluons of the proton, the convergence of this expansion is relatively slow and in certain cases computations with three or four terms are required. The problem with this approach is that the Feynman diagrams, which appear in the individual terms of this expansion, rapidly increase in both number and complexity. To make matters worse, these Feynman diagrams also contain complicated infrared (IR) and ultraviolet (UV) divergences (singularities) which are of long- and short-distance origin. While the problem of UV divergences has been solved already half a century ago by the procedure of renormalisation, the situation is very different for the IR divergences. Calculating higher-order effects in QCD requires the combination of two separate contributions: real corrections (due to emissions of observable particles) and virtual (loop or quantum) corrections. While it is well known that the divergences of the real emission corrections cancel with those of the virtual corrections, the cancellations only happen after all the different loop and phase-space integrals have been performed. A rigorous approach to renormalisation is given by the Bogoliubov-Parasiuk-Hepp-Zimmermann (BPHZ) scheme also known as the "forest formula", where the term forest refers to sets of nested or disjoint divergent subgraphs. The key idea of this project is to develop and use "generalised forest formulas" for the subtraction of IR divergences. While this proposition is far from trivial, recent breakthroughs which I have made in my recent research have already proven the concept, obtaining a plethora of new results which could not have been achieved by other means. The future potential of this approach is great, as it opens the door for new ways of calculating quantities, which are desperately needed to improve the precision of current theory predictions, such as the 4-loop splitting functions, which govern the energy dependence of partons in the proton, and the 2-loop anomalous dimensions which govern the energy dependence of coupling parameters in the SM EFT, a general model-independent framework to BSM physics.

UKRI Gateway to Research · FY 2024 · 2024-09

The Cambrian Radiation, starting ca. 540 million years ago (Ma), marks the appearance of abundant and diverse animals (metazoans) in the fossil record. This radiation may have been driven by oscillating ocean oxygenation and productivity events, but was terminated by the first mass extinction, the 'Sinsk Event', ca. 513 Ma. The Sinsk Event is considered to have been a hyperthermal interval of widespread ocean anoxia that reset the trajectory for all subsequent metazoan life. However, despite its significance for the course of Earth's habitability and the evolution of complex life, little is known about the drivers of this event, or which environmental factors controlled extinction selectivity. We hypothesise that it was low oceanic sulphate levels that promoted oscillating oxygenation, so creating pulsed metazoan radiations, but paradoxically this also made the early Cambrian shallow ocean highly susceptible to anoxia in response to global warming, thereby terminating these radiations with a profound extinction. We propose an ambitious integrated palaeobiological, geochemical and modelling approach to unravel the controlling processes of radiations, and the consequences of the enigmatic, but highly significant, Sinsk Event. By comparing the drivers of the Cambrian Radiation with those of its demise, we will address a fundamental motivating question: Did low sulphate seas both promote radiations and drive extinctions through Earth History?

UKRI Gateway to Research · FY 2024 · 2024-09

Our research program seeks to answer key open questions on the origin of the elements in stars, the processes responsible for stellar explosions, and the behaviour of nuclei at the limits of existence. The experimental study of astrophysical reactions and nuclear properties requires cutting-edge instrumentation and suitable facilities for stable-, neutron-, and radioactive ion beams, as well as ion traps and decay spectrometers. The Group is uniquely well placed to exploit these capabilities at world-leading laboratories and has a strong track record in developing innovative instrumentation to match the unique requirements of different reaction- and nuclear properties studies. Over the coming grant period we will initiate a program of reaction studies at the LUNA underground facility to investigate the origin of carbon, nitrogen, and oxygen isotopes in first-generation stars and to explore alternative neutron sources for the early synthesis of heavy elements. Also at LUNA, we will exploit the recent installation of a new 3.5MV accelerator to investigate open questions on the core metallicity of the Sun, carbon fusion in massive stars, and neutron source reactions for the slow-neutron capture process. At the n_TOF (CERN) neutron beam facility, we will lead a rich program of neutron-induced reaction measurements, for example to explore the origin of radioactive 40K, believed to be responsible for heat generation in rocky exoplanets, elucidate the origin of rare pre-solar stardust grains with peculiar abundances of Si and S isotopes, and study the destruction of the cosmic gamma ray emitter 26Al in massive stars. We plan challenging neutron activation measurements on radioactive samples to help explain abundances of certain metal poor stars, and the origin of nature's rarest isotope 180mTa. Also at CERN, we plan to improve on our previous investigations of 44Ti-destruction to shed light on the final stages of supernovae explosions of massive stars. Storage rings will provide game-changing opportunities to study reactions with radioactive isotopes relevant to explosive astrophysical scenarios, by delivering both increased beam purity and intensities otherwise unavailable anywhere else in the world. At the Experimental Storage Ring at GSI we will explore the origin of some light p-nuclei, whose abundances are consistently underproduced by stellar models of core-collapse and type Ia supernovae. The Group has approved experiments to exploit the recently commissioned Edinburgh-built CARME detection system at the CRYRING storage ring to study key reactions of novae explosions. With beamtime already approved at TRIUMF we will investigate reactions involved in the production of 18F, a main cosmic-ray emitter from novae, and in the break-out from the Hot-CNO cycle in X-ray bursts. The Group has developed state of the art ion traps and radioactive decay detection systems to investigate masses and decay properties of exotic nuclei across wide areas of the nuclear landscape. Over the grant period, we will lead a program of high-precision mass measurements of neutron-rich light nuclei near closed shells as unique testbeds for modern nuclear theories. Further mass measurements of neutron-rich heavy nuclei will provide constraints to explosive nucleosynthesis in the r-process. Such studies will be complemented at RIKEN by decay measurements of nuclei in the rare-earth region by exploiting unique experimental capabilities including the Edinburgh-built AIDA device. Mass measurements near the proton-drip line will shed light on the limits of nuclear binding, while proton and alpha decay studies at Argonne will offer unique insights into the effect of nuclear shape on quantum tunnelling rates. With novel ion trapping devices developed in Edinburgh we will investigate exotic decay modes and radioactive molecules with potential for physics beyond the standard model and medical applications.

UKRI Gateway to Research · FY 2024 · 2024-09

The first direct detection of Gravitational Waves generated by the encounter and merger of two black holes was made by the Laser Interferometer Gravitational-Wave Observatory in 2015. Since this discovery, several other events which also include neutron stars have been observed. This opens a new path to explore the Universe and the limits of General Relativity. The analysis of these events requires precise prediction for the waveform signal templates at the interferometer, which are obtained by a combination of different methods to attain a good theoretical prediction of the three phases of a binary merger: the inspiral, merger, and ringdown. In the past years, motivated by the discovery of Gravitational Waves, new efficient ways to produce predictions to model the binary inspiral have emerged. In contrast with traditional methods, these approaches are based on quantum field theory methods. The success of this effort borrows years of development in tools from precision physics for colliders. Such tools include new variables, multiloop calculations, and a formalism to obtain classical observables from quantum scattering amplitudes. In this project, we aim to push the state-of-the-art in the description of spinning generic compact bodies (e.g. black holes and neutron stars), including non-conservative and absorption effects, in order to understand quantum-to-classical transitions with scattering amplitudes. We are going to progress in combining tools to efficiently go to higher-loop order in the conservative and nonconservative effects relevant to gravitational wave experiments. In this endeavor, we plan to explore relations and conjectures emerging from quantum-to-classical transitions.

UKRI Gateway to Research · FY 2024 · 2024-09

This grant award is for the purchase of eInfrastructure (CPU, storage and networking) as part of the IRIS consortium. IRIS supports STFC Science Projects, including the National Facilities and Science Programmes.

UKRI Gateway to Research · FY 2024 · 2024-09

Motor neuron disease (MND) is an incurable, rapidly progressive, and fatal neurodegenerative disease. It affects motor neurons, causing prominent difficulties with movements, walking, speech and breathing. Most affected people unfortunately do not survival beyond 1-2 years, and only a single drug has been shown to marginally benefit survival by 2-3 months. Progress to deliver new and effective treatments have been hampered by difficulties in timely diagnosis, identification of subtypes, and monitoring of disease severity. Current standard investigations and tests are often invasive, time-consuming, subjective, and crude. There is clear urgent and unmet need for more sensitive and high frequency data that reflects individual impact of disease to facilitate diagnosis and monitoring which are accessible and acceptable to people living with MND. Speech is profoundly affected in MND and offers unique potential as a non-invasive biomarker. Advances in digital technologies and artificial intelligence (AI) to study speech are opening a new era of opportunities in disease diagnosis and monitoring. This project aims to develop digital speech biomarkers, derived using accessible digital devices to identify patterns in speech which are sensitive to changes seen in MND. We developed a user-friendly and widely accessible App for smartphones, tablets and computers in a co-production process with participants, specialised in the collection of speech data from people living with neurodegenerative conditions. Speech recordings are analysed using state-of-the-art AI approaches to derive digital biomarkers, which will be evaluated to assess their performance in supporting diagnosis and monitoring of MND The major benefit of this approach is the ease and non-invasiveness of speech recordings which can be collected remotely and at scale, offering an opportunity for earlier diagnosis and closer monitoring in MND. Applications include screening individuals suspected of MND, and providing sensitive measures of disease severity for clinical care and drug trials. This would reduce patient burden and provide additional valuable information to healthcare professionals, such as alerting clinicians to significant events like breathing or swallowing difficulties to prompt earlier interventions. This will ultimately benefit carers, relatives, and healthcare professionals by enabling better understanding of MND progression and facilitate appropriate care planning. Digital speech biomarkers have a unique potential to significantly improve the care and research for people living with MND. This translational AI research project will develop these tools for use in MND clinical and research practice.

UKRI Gateway to Research · FY 2024 · 2024-09

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

UKRI Gateway to Research · FY 2024 · 2024-09

MolCal will contribute to establishing a critical mass of researchers in promising exploratory topics on caloric materials and energy conversion technologies for solid-state cooling and heating applications at near-ambient and very-low temperatures. Temperature control systems are responsible for approximately half of the EU energy consumption expenditure. This figure alone amply justifies the need to dedicate great efforts to the search for alternative refrigeration and heat pump methods. Research on caloric materials has never been as active as it is now, due to the prospect of new-generation refrigerators and heat pumps that are energy efficient and environmentally friendly, on the one hand, and the policies on low-energy consumption and global warming refrigerants, on the other. MolCal presents an approach never tried before in similar collaborative research training programmes. We will consider caloric materials that fall under the umbrella of molecule-based materials and can respond to different sources of the driving stimulus, be it magnetic, electric, and/or mechanical. Since there is no clear-cut consensus on which type of caloric material holds the most promise, this multi-front approach will be an advantage because it will permit transfer of methods already developed from the magnetocaloric subfield into the others, which are increasingly in the spotlight because of their enormous potentiality. Furthermore, MolCal will develop devices based on low-cost barocaloric materials and, due to the molecular characteristics, will progress towards challenging applications by exploring the limits of the smallest size of magnetic refrigerators. Academic and non-academic leaders, from top research institutions in Europe and outside, will expose the doctoral researchers to integrative, multidisciplinary, and multisectoral training in chemistry, materials science, physics, device development, and relevant transversal skills.

UKRI Gateway to Research · FY 2024 · 2024-09

Antibiotic resistance happens when bacteria become resistant to the drugs that were designed to kill them. This means that the drugs become less effective at treating infections. It can lead to the development of superbugs that are very difficult and sometimes impossible to treat, leading to longer illness, higher healthcare costs, and in severe cases, death. Antibiotic resistance is considered a major global health threat that already causes disruption to health services and leads to many deaths every year. Unless we find ways to limit the development and spread of resistance, it is set to become worse, and with many treatments and surgeries relying on antibiotics to prevent infections, resistance has the potential to uproot modern medicine as we know it. Resistance can evolve naturally over time, but this is often accelerated by the overuse or misuse of antibiotics. Antibiotic tolerance is a major bottleneck in designing responsible treatment strategies that optimise the use of antibiotics. Tolerance is when bacteria can survive exposure to antibiotics that would normally kill them. This happens before resistance develops and typically requires higher doses of antibiotics or longer treatment. We propose to study a type of tolerance that allows bacteria to keep growing when exposed to antibiotics that target the ribosome, which is the core molecular machinery that produces proteins needed for cellular function and growth. Recent research has shown that when bacteria are exposed to these drugs, some of the cells activate a specific molecular repair system, the Rtc system, and that these cells can keep growing despite the antibiotics. The Rtc system helps cells repair damaged RNA, which performs many vital functions in cells and makes up a sizeable part of the ribosome itself. We seek to understand how RNA repair by Rtc helps bacteria survive antibiotics. We will study how Rtc interacts with ribosomes and how this affects the growth of individual bacterial cells. We will use data to create a computer model that describes the detrimental actions of antibiotics to ribosomes and the counter repair actions of Rtc. Computer simulations are much faster than real-world experiments, and so can help us speed up the development of new scientific insights and solutions, which typically require lengthy rounds of trial-and-error experiments. The computational model will be able to predict how bacteria will respond to antibiotics, and it will help us understand why some bacteria are more tolerant than others and how they can switch between tolerant and susceptible states. We will use the model to help us produce new hypotheses on how to develop better treatments for infections, which will guide future experimental work and shed light on how to slow down the development of resistance.

UKRI Gateway to Research · FY 2024 · 2024-09

High density building areas within cities and towns have the greatest challenges in meeting net zero targets and are ‘keystones’ of the future UK green economy. Diverse complexities of building archetypes, multi-use, historic and ‘listed status’ planning constraints requires a range of innovative low carbon green solutions. This is a critical net zero challenge not just for the UK (6M buildings) but also globally with 55% of the world's population living and working in urban areas, rising to 68% by 2050. This offers a significant major market opportunity for innovative co-designed UK-based manufactured solutions.   The city regions of Edinburgh and Glasgow have the highest density proportion of flats in UK cities at 68% and 73% versus London 46% (UK average 19%). Over the next 20 years both cities combined will have a £35 Billion net zero retrofit requirement for existing buildings, including over 200,000 pre-1919 stone buildings and World Heritage streetscapes. They offer the unique potential of being the green economy UK pathfinders and primary pilot city regions for hosting a Centre for Net Zero High Density Buildings (CeNZ-HighDB).   CeNZ-HighDB combines world leading expertise involving five regional universities (Edinburgh, Glasgow, Strathclyde, Napier and West of Scotland) with 58 partner organisations to design, develop and deliver inclusive net zero solutions for high density buildings and city-town streetscapes. This £10M Centre partners with UK construction industry, product manufacturers, energy companies, public bodies, housing organisations, communities and colleges to accelerate societal critical green economy pilot and prototype projects.   Utilising a whole system co-designed led approach with industry and public sector the Centre will develop, test and underpin delivery of identified new ‘green’ innovations including high-energy efficiency building fabrics, new lower cost rapid-fit heating technologies, novel community heating-cooling systems for complex multi-use streetscapes and advancements in thermal-cooling modelling and data driven innovation to drive green economy growth. A major proportion of the UK’s key workers, low-income households and disadvantaged groups live in high density buildings and the Centre’s impacts will enable reduced energy costs, substantial carbon emission reductions and accelerate 'inclusive' retrofit delivery for social housing sectors and urban buildings.   Importantly CeNZ-HighDB will partner with regional skills academies and colleges to accelerate future deployment of innovative product and technology solutions co-developed with industry partners. Our networks within colleges and industry will provide established pathways to roll out new training courses accelerating green economy growth and enhancing EDI outcomes pan-UK.   Early mapping of 50+ partner co-developed projects constitutes a rapid Centre development pipeline that will: create over 2,000 new regional green jobs with award winning regional skills partners; support net zero transition by upskilling over 6,500 British Gas installation engineers and deliver over 600 manufacturing industry jobs. CeNZ-HighDB will engage with policy makers, technical standards bodies, building control, other HEI’s expertise and health and safety advisors to maximise reach of the centre’s whole-systems approach enabling wider impact and engagement addressing synergetic high-density buildings ‘grand challenges’ across the UK.   CeNZ-HighDB brings together a critical mass of world leading expertise, innovative partner companies, major city and housing organisations to accelerate net zero green outcomes, economic growth and societal benefits firstly for the city regions and then more widely pan-UK. It will provide international export growth opportunities for UK companies through co-developed solutions underpinned by prototype/pilot ‘real-site’ and ‘living-lab’ based evidence.  

UKRI Gateway to Research · FY 2024 · 2024-09

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

UKRI Gateway to Research · FY 2024 · 2024-09

The proliferation of the global wildlife trade has increased the risk of disease spill-over into human, wildlife, and farmed animal populations, with potentially catastrophic consequences. Increasing capacity for rapid and inexpensive diagnosis of disease in wildlife to understand the source of the traded items and the disease risks is a crucial step towards tackling this significant issue. Few diagnostic platforms explicitly combine disease and wildlife diagnostics, following a One Health approach; currently, the analysis of a trade item typically involves the use of different tests performed in different laboratories to identify pathogens and their associated wildlife host. Further, utilising high-throughput sequencing in wildlife diagnostics is impractical for most laboratories due to the monetary and time costs required, or its use is limited to specific species/pathogen groups. I propose to harness recent advancements in DNA sequencing and a novel 'adaptive sampling' technology that allows users to target specific DNA sequences in real-time using state-of-the-art software. This innovative adaptive sampling approach simply requires the user to input the relevant diagnostic genetic markers into a computer program; these genetic markers are then targeting during DNA sequencing, without prior laboratory enrichment steps. I will leverage these technological advances to develop and optimise a workflow capable of detecting pathogens and their wildlife vectors in a single assay. Simultaneous analysis of host and pathogen species to inform population disease risk, biodiversity conservation and law enforcement in a wildlife trade scenario, is novel and multi-faceted in application. This research will therefore provide advanced and interdisciplinary experience for the Fellow, directly aligning with the goals of this Call. Project outcomes will inform a blueprint to implement adaptive sampling in other wildlife diagnostic systems, and in applied genetics more broadly.

UKRI Gateway to Research · FY 2024 · 2024-08

Churches carved into the rock have a story to tell. Despite their large number world-wide, they have not received as much attention as masonry-built churches in archaeological studies. This situation is usually explained by the difficulty to date these structures, by the lack of knowledge on their place within local historical landscapes and on their biography as living heritage. These issues have prevented researchers from using rock-cut churches as valuable sources to investigate the Christian communities and the settlement history of their landscape. The innovative project Rock-cut Architecture and Christian Communities in Turkey, from Late Antiquity to 1923 (RACCTURK), focuses on these issues by developing a mix-method approach and asking original questions: How much do rock-cut churches contribute to the understanding of economic structure, social networks and occupation strategies of religious rural communities over time? The project will take place in Cappadocia (Turkey), focusing on the valley of Koramaz - inscribed on the tentative list of UNESCO - where a dense network of rock-cut churches is preserved as well as built and rock-cut monuments from Antiquity until the departure of the Christian communities from the region in 1923. The project' multi-method merges historical landscape characterization method, building archaeology, social anthropology, geology and geomatics. It aims to provide researchers with methodological and theoretical landmarks to reconsider rock-cut churches as valuable archaeological sources. RACCTURK will promote Cultural Heritage and Intangible Cultural Heritage for the benefit of rural communities, strengthen the research exchanges between European and Turkish scholars as well as partnership between private and academic sectors in the Cultural Heritage promotion. By providing digital tools on the Cappadocian Christian Cultural Heritage, RACCTURK will help to develop sustainable tourism oriented towards European citizens.

UKRI Gateway to Research · FY 2024 · 2024-08

Precious metals such as palladium or gold can be implanted finely sliced into tumours with the aim of activating chemotherapeutic drugs within the cancerous tissue, thus reducing their side effects. The development of antibodies directed towards tumour surface antigens is investigated as a novel targeted strategy with the aim to promote the release of drugs in a controlled manner exclusively at tumour sites. The Unciti-Broceta Group propose the use of palladium, an abiotic metal, to develop Antibody-Palladium Conjugates (Pd-bioconjugate or Pd-Immunoconjugate) as catalytic cancer targeted antibodies in order to kill cancer cells/tumors by the localised release of clinical anticancer agents (prodrugs).

UKRI Gateway to Research · FY 2024 · 2024-08

Minimal quantities of historical writing in Latin survive from the period between c. 120 and the history of Aurelius Victor in 360, and it appears little was ever written. Our knowledge of Roman imperial history of the second, third, and fourth centuries of our era - the period after the first twelve Caesars - therefore derives disproportionately from a group of Latin secular historians writing in the later fourth century. The Last Historians of Rome project offers a fundamental reassessment of two long works, the Res Gestae of Ammianus Marcellinus and the pseudonymous Historia Augusta, and four short texts, two attributed to Victor, as well as the breviaries of Eutropius and Festus. The project aims to transform the understanding of these historians, both individually and as a coherent group, and to massively improve their accessibility to scholars, students, and the wider public. There is much to be done. These works are not normally associated with each other: Ammianus, whose coverage of the years 96-353 is lost, is seen as an outstanding contemporary historian, the shorter works as trivial and error-prone bluffer's guides to Roman history, and the Historia Augusta's imperial biographies as an unreliable imposture verging on fiction. The standard editions are either inadequate, or a century old; the manuscript transmissions have been misunderstood and under-investigated. Two still have no conventionally published English translation, and none has a really high-quality, comprehensive, and accessible one. New insights and discoveries, including by the Project Leads, make a fresh presentation through a reedited text and translation even more urgent. For Ammianus, Kelly has published widely on the need for further conjectural emendation, has brought new insights on prose-rhythm's role in editing, and has reassessed the relationships of the Renaissance manuscripts and, with Stover, the Carolingian ones. Stover and Woudhuysen have demonstrated that the two Victorine works are actually summaries abbreviated from Victor's original by others. For the Historia Augusta, Stover has identified multiple sources for a neglected second branch of the manuscript tradition including passages that have been omitted in editions for centuries. At the centre of the project are new critical editions of these historians for the Oxford Classical Texts series. New editions are among the most important and challenging tasks that can be undertaken in Classical Studies, especially for works whose standard editions are outdated, inadequate, or both. Their useful life can last many decades, and they are essential for every scholar, classicist or medievalist, literary or historical, who studies the authors or uses them as a source. We will publish new annotated translations, making these texts accessible to enthusiastic amateurs and teachable in Anglophone universities. A catalogue assessing the manuscripts and early printed editions, an Onomasticon of the historians, and subsidiary textual studies will both aid the preparation of the editions and stand as important independent scholarly contributions, some of interest beyond Classical Studies. The three Leads will also co-author a short book interpreting the historians as a coherent group and reassessing their place in the development of Roman historiography.

UKRI Gateway to Research · FY 2024 · 2024-08

Studies investigating effects of nanoplastics (NPs) on aquatic organisms used concentrations between 2 to 7 order-of-magnitudes higher than those predicted in ocean to track NPs. 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. In reality, most experiments were inadequately designed. Fit-to-purpose experimental designs have been hindered by a lack of appropriate NP models, tracking methods, and monitoring strategies for environmentally realistic concentrations. Using 14C-labelled NPs and conventional nuclear techniques, we recently modelled that scallop, chronically exposed to environmentally realistic NP concentrations (15 ug/L) might accumulate and reach NPs body burden where effects are observed by those sounding the alarm. Astonishingly, this suggests that NPs are already beyond threshold-effects in organisms and harming the marine biota. UNSEEN will investigate whether NPs in the oceans are already beyond "threshold-effect" concentrations? Using a successful radiolabelling approach, UNSEEN will establish a new methodology for correlative imaging of NPs with elemental and molecular imaging using ion beam analysis (IBA) and mass spectrometry imaging (MSI). This analytical approach will provide a unique insight into the potential effects of NPs. The overall goal of UNSEEN is to go beyond a mere qualitative evaluation of the distribution of NPs in the food web, and to generate quantitative, spatially-resolved toxicokinetic and metabolomic data. Quantitative tissue distributions of NPs, following realistic chronic NP exposures, will be directly compared to the spatially-resolved metabolomic data. This will provide a proof-of-concept for a truly novel approach. UNSEEN addresses key questions of whether NPs accumulate in the food-web and whether NPs are harming aquatic organisms at environmentally realistic concentrations after long-term exposures. The approach proposed here is essential and will produce unique, valuable and fundamental knowledge on the combined long-term consequences of NPs and their additives in aquatic environments. This is critical for developing appropriate management strategies regarding plastic litter. If successful, UNSEEN will indeed support policy makers in improving environmental risk assessments of NPs. It is envisioned that the approach proposed herein will enable a step-change in the research on contaminants of emerging concerns and will allow the study of many different aspects of their fates (e.g., transformation, fragmentation, biomineralization, biodistribution). The unconventional approach will fully integrate the processes that govern the biological responses to NPs and provide an understanding of the potential effects of NPs that could be translated to human health. UNSEEN chooses a highly innovative approach to address its research questions. It combines radiochemistry and very emergent technologies from biomedical sciences using ion beam analysis (IBA) and mass spectrometry imaging (MSI) to resolve important environmental questions. It will establish 14C-labelled NPs as a gold standard for performing realistic laboratory-based studies. It is fundamental research that will have a critical impact beyond its overall goal. The research proposed will, for instance, have a huge impact on the use of 14C as low-level tracer in biomedical studies (i.e. micro-dosing), where appropriate methods are often missing. The approach proposed is unique and will allow to perform ground-breaking science that goes beyond the state-of-the-art. UNSEEN builds a unique inter-disciplinary research team that integrates the relevant expertise in environmental analytical chemistry, radiochemistry and ion beam physics.

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 in order to be able to track NPs. 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. In reality 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, tracking methods, and monitoring strategies for environmentally realistic concentrations. Using 14C-labelled NPs and conventional nuclear techniques, we have recently modelled that scallops, chronically exposed (over a year) to environmentally realistic NP concentrations (15 ug/L) might accumulate and reach NPs concentrations in body tissue where effects have been 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, we will deliver an innovative approach that will overcome the analytical limitations for detecting, mapping and quantifying NPs in realistic environmental settings. By combining 14C-labelling of NPs with the ultimate sensitivity of Accelerator Mass Spectrometry (AMS), METABOLISM will allow to investigate whether NPs in the oceans are already beyond "threshold-effect" concentrations in tissues. METABOLISM will: i) provide representative intrinsically radiolabelled NP models; ii) perform chronic NP exposures with a model organism (i.e. mussels) at environmentally realistic NP concentrations (ppt-levels); iii) develop the combustion AMS to generate toxicokinetic data; iv) explore the LA-AMS to produce spatially-resolve 14C measurement to quantify tissue distribution of NPs. The approach proposed here is essential and will produce unique, valuable and fundamental knowledge on the combined long-term accumulation of NPs in aquatic environments. This is critical for developing appropriate management strategies regarding plastic litter. If successful, METABOLISM will indeed support policy makers in improving environmental risk assessments of NPs and other contaminants of emerging concerns (CEC). It is envisioned that the approach proposed herein will enable a step-change in the research on CECs and will allow the study of many different aspects of their fates (e.g., transformation, fragmentation, biomineralization, biodistribution). METABOLISM chooses a highly innovative approach to address its research questions. It combines radiochemistry and unlock the power of the AMS to resolve important environmental questions. It will establish 14C-labelled NPs as a gold standard for performing realistic laboratory-based studies. It is fundamental research that will have a critical impact beyond its overall goal. The research proposed will, for instance, have a huge impact on the use of 14C as low-level tracer in biomedical studies (i.e. micro-dosing), where appropriate methods are often missing. The approach proposed is unique and will allow to perform ground-breaking science that goes beyond the state-of-the-art. METABOLISM builds an inter-disciplinary research team that integrates the relevant expertise in environmental analytical chemistry, radiochemistry and physics.

UKRI Gateway to Research · FY 2024 · 2024-08

This project will put class at the centre of the historical reconstruction of ancient Greek democracy. It contends that class dynamics - grounded in the economic and occupational structures of the Greek cities, and manifesting themselves in the social, political, and cultural oppositions that characterised them - are fundamental for understanding the emergence, nature, and development of Greek democracies. This perspective finds much purchase in our sources, both in direct evidence for political struggles and in contemporary political reflection. Class, for instance, plays a central role in Aristotle's analysis of contemporary politics. In his view, the citizenry of any polis could be divided into two parts, the rich and the poor, with further, complex subdivisions based on occupation, and he tightly links the constitution of any given city to the socio-economic organisation of its citizenry. For this keen observer of the politics of his day, then, thinking about Greek politics in terms of class is indispensable. Yet class has been all but abandoned as an explanatory concept by most modern scholars of ancient Greek politics, not to mention by social and economic historians. It is this project's contention that a more flexible notion of class, integrating the best Marxist historiography with recent work in sociology, allows us to put this concept back where Aristotle placed it: at the heart of the analysis of ancient Greek politics and society. The project will explore the economic underpinnings of class relations in the Greek city-states; the cultural tastes and social lives of different groups, and how they were structured in opposition to one another; and how these class oppositions coalesced in certain political preferences and in particular ideological and institutional options. It aims to achieve nothing less than a revolutionary reconceptualisation of the driving dynamics of the society and politics of the ancient Greek city-states.

UKRI Gateway to Research · FY 2024 · 2024-08

Artificial Intelligence has altered and in future going to influence the way our economies and societies are organised and function. The economic systems are increasingly being digitalised which has generated the growing chorus around digital economy. Digital data-fuelled devices be it in our homes or workplaces, are shaping human interactions. The machines of today are going to define the human life of tomorrow. While the bold proclamations about digital technologies and their development impacts have received extensive coverage, it is rarely acknowledged that behind most contemporary digital transformations and advanced digital technologies is human labour. Just like the profitable commodities of earlier decades (oil, diamond, gold), contemporary digital products (autonomous vehicles, machine learning systems, next-generation search engines) are sourced and developed by workers in the low and middle-income regions. It is this behind-the-scene human labour that faces uncertain future. The centrality of labour from the Global South in some of these technologies raises critical questions around the new division of labour, developmental impacts for workers, and what the future would look like for workers on the continent and also other low and middle-income regions. The project explores these issues about our rapidly changing world of work and the implications on humans and regions that motors the global digital economy. The four-year project uses mixed methods to conduct a comprehensive empirical and theoretical assessment of behind the scene human labour in the Global South and leverage cross-country project partnership to develop analytical insights into the data work value chains of AI. By bringing theoretical sophistication and grounded empirical insights, the project's overall contribution is to unravel the geographies of data work and its implications for LMIs. The Planetary AI project will: (1) develop conceptual frameworks for studying data work value chains and labour market transformation, (2) generate empirical data on the scope of data work across the four case study countries and its developmental impacts (e.g. access to decent work), (3) produce research outcomes useful for academia, policy and practice. By combining discourse analysis, surveys, in-depth interviews, it captures the socio-political and economic transformations associated with the rise of data work across the Global South. Hence, the project contributes not only to the academic and policy debates surrounding AI, employment, and poverty reduction but will also be crucial in shaping the future rounds of digital-related development projects in low- and middle-income (LMI) countries. It also addresses policy-level changes required to protect the vulnerable sections of the society who are affected by the changing dynamics of technology and work. To make sure the project reaches a wider audience, it has developed multi-stakeholder networks of project partners. The ILO, business owners, policy makers, and data workers will be closely involved. Their expertise and networks will ensure it reaches actors who can influence the world of work. This is urgently needed as the risks of AI use has exposed the need for adequate regulatory reforms so that workers in the Global South are protected in their everyday lives. This project provides tools and evidence to ensure that such reforms are designed to strengthen policies related to labour standards, employment law, and social protection in the Global South and beyond.

UKRI Gateway to Research · FY 2024 · 2024-08

Selective breeding has played and will continue to play a pivotal role in increasing the productivity and welfare of farmed animals, including Atlantic salmon. Its significance in all farming systems is expected to grow as the industry grapples with the challenges posed by climate change, including the spread of infectious diseases. While selective breeding is able to enhance most desirable traits, genetic progress is limited by multiple factors as defined by the breeder´s equation, namely selection intensity, accuracy of selection, presence of genetic variation and generation interval. In Atlantic salmon aquaculture, genetic progress is notably slow, primarily due to the extended 4-year generation time. This issue is exacerbated for traits characterised by low to moderate genetic variation, especially those, such as disease resistance, which cannot be measured in the selection candidates. Disease resistance, along with growth, constitutes the main target of aquaculture breeding programmes. Given the prominent position of Atlantic salmon aquaculture in the British economy as one of the foremost food exports, expediting genetic improvement in Atlantic salmon with respect to disease resistance is not only poised to deliver substantial advancements in animal welfare but also major societal and economic benefits. Over the last decades, the focus of aquaculture has predominantly centred on refining the precision of selection through enhanced statistical models, while other factors have been mostly overlooked. This project will take a comprehensive approach to accelerate genetic gain in Atlantic salmon via complementary interventions targeting generation time, phenotypic accuracy and genetic variation, while aligning with the principles of the 3Rs and reducing animal usage and harm. Two distinct strategies will be explored to diminish generation time. One involves inducing early maturation in males through modifications to light and temperature rearing conditions, while the other concentrates on in vitro expansion of germline stem cells to enable in vitro sperm generation and surrogate broodstock strategies. The objective is to reduce male generation time between 4 to 8 fold, increasing the overall rate of genetic gain in the breeding programme 2-4 times. Both strategies can be coupled with in vitro phenotyping of disease resistance, using cells to determine the differences in response to infection directly in selection candidates. This approach can provide more accurate disease resistance phenotypes while reducing the need for animal experiments. Furthermore, the project seeks to establish protocols for genome editing of salmon germ cells. This breakthrough will facilitate the efficient incorporation of favourable genetic variation into salmoniculture, allowing breeding companies to produce both edited and non-edited fish from the same broodstock, accommodating diverse legislations. Each of the approaches, when considered individually, holds the potential to increase the rate of genetic gain, thereby enhancing industry sustainability and animal welfare. When implemented in concert, this project can reshape current Atlantic salmon aquaculture by allowing speed breeding of disease resistance traits. The envisioned breeding programme, equipped with male speed breeding and disease resistance in vitro phenotyping, is poised to achieve significant genetic gains in disease resistance while minimizing the reliance on costly and harmful animal experiments. This model can be further integrated with large-scale genome editing to produce edited animals with enhanced characteristics for countries with favourable legislation. In summary, the project aims to revolutionize Atlantic salmon aquaculture, ensuring the welfare of our farmed animals and the sustainability of the industry in the face of a changing world.