UNIVERSITY OF EDINBURGH

UKRI Gateway to Research · FY 2024 · 2024-06

The world is facing a health crisis caused by an ageing population with poor health. In 2025, about 1.2 billion people will be over the age of 60, and this will increase to 2 billion by 2050. While an increase in lifespan may be desirable, this does not coincide with an increase in healthspan (the length of time an individual is able to maintain good health), and the elderly often suffer from frailty and poor health. Lipids or 'fats' in the blood change as we age, and some lipids are associated with poor health. Changes in the diet, such as caloric restriction, reduce lipids associated with poor health and are associated with longevity in model organisms such as mice. This proposal aims to understand how lipid-changes during ageing affect our immune systems, which deteriorate as we age and promotes poor health. Ageing particularly affects a type of immune cell, called a T cell, whose primary function is to kill virally-infected or malignant cells. This leaves older individuals susceptible to infections by viruses such as Influenza (that causes flu) and SARS CoV2 (that causes COVID-19). As demonstrated by the SARS CoV2 pandemic, elderly individuals had much higher morbidity and mortality than the younger population. In addition to chronological age, biological age also affects immune deterioration, and as such many other factors contribute to severe illness associated with COVID-19, including having cancer, having a chronic infection, being overweight or obese, having diabetes, or being immunocompromised. Understanding the biology of healthy ageing is of paramount importance as we strive to find ways to expand the healthspan in an ageing population. Mitochondria are organelles that generate an important fuel for biochemical reactions called adenosine triphosphate (ATP). Mitochondria are very efficient at generating ATP, and are considered "the powerhouses of the cell". Mitochondrial dysfunction is a primary hallmark of ageing. Mitochondrial dysfunction in T cells impairs their normal function and accelerates ageing, but the cause of mitochondrial dysfunction during ageing is not understood. Lipids are key regulators of mitochondrial function. Lipids in the mitochondria are important as membrane components, as signalling mediators, and for energy production. This proposal aims to understand how lipids regulate T cell ageing and interlinked mitochondrial function. The outcome of this proposal will be new insight into the mechanisms underlying T cell ageing in the healthy UK population.

UKRI Gateway to Research · FY 2024 · 2024-06

Intracerebral haemorrhage (ICH) causes one quarter of strokes worldwide. Over a third of people with ICH die within a month, and survivors are often disabled. In the UK, at least one in twenty ICH survivors has a stroke, heart attack or dies each year. With such a devastating disease, prevention is vital. To prevent ICH happening, we need to understand the differences between those who have the disease and those who do not. The strongest risk factors for ICH are high blood pressure and high alcohol intake, but they are both very common in the general population. Many other medical conditions are linked to ICH, but the link is much less strong. Most people with ICH have more than one risk factor, and lots of other medical conditions. Some medical conditions may group together in particular people, and increase risk of ICH, or poor outcome after ICH. OPPORTUNITY Because ICH is not common, most studies have been small and studied one risk factor at a time. We do not know how having multiple medical conditions changes the risk of ICH, its outcome and treatment, or if specific combinations of medical conditions are particularly important. Recent advances in health data can improve research into multiple medical conditions. Routinely-collected healthcare data is available securely to researchers in Scotland. The UK Biobank is a research study of half a million people, with brain scans and genetic data. Data from large clinical trials can tell us how different types of people respond to treatments. OBJECTIVES The objective of this study is to understand how having multiple medical conditions affects risk of ICH, and outcome after ICH. This study has three parts: I plan to use machine learning to analyse large databases. I will identify groups of people with similar combinations of medical conditions. I will compare these groups, to see if there are differences in ICH occurrence, ICH appearance on brain scans, and the ongoing health of people after ICH. In an upcoming study testing aspirin after ICH, I will see whether having multiple medical conditions affects whether people choose to take part. I will examine if having multiple medical conditions affects how well people respond to treatment in clinical trials. BENEFITS The Chief Medical Officer for England, Professor Chris Whitty, has highlighted multiple medical conditions as a key area of research. Better understanding of multimorbidity in ICH could allow us to improve our understanding of the cause of disease, organise services to meet peoples' needs, and improve prevention and treatment. Furthermore, the project is a valuable opportunity for me, as an early-career researcher, to receive training in the fundamentals of epidemiology, medical statistics and machine learning, and to launch a career as a clinical academic.

UKRI Gateway to Research · FY 2024 · 2024-06

Few problems in fundamental physics are as clearly motivated or as important as discovering the nature of the elusive dark matter that accounts for most of the mass of the universe. Direct detection experiments located deep underground are searching for the rare interactions of these theoretically well-motivated particles using very sensitive detectors. Liquid xenon (LXe) technology has led these searches for over a decade. Recently, the top international collaborations in the field have come together in the XLZD consortium to build the definitive experiment: one able to discover or rule out leading particle dark matter candidates, down to the point where the sensitivity is so high we will see significant backgrounds from neutrinos. Exciting opportunities also exist in neutrino physics, including establishing the existence of neutrinoless double-beta decay; this is another paradigm-shifting discovery which may be accessible through such an experiment, which could explain the matter-antimatter asymmetry in the universe. This proposed 'rare event observatory' will deploy a LXe detector with up to 80 tonnes of 'active' mass in an ultra-low-background experiment to address these and other questions, at least two of which could entail Nobel-Prize worthy discoveries. This Pre-Construction project prepares the UK contribution to the XLZD experiment and builds the case to bring this ambitious international experiment to the UK. STFC is developing a major new underground laboratory at the Boulby mine, and XLZD would be the centrepiece of the new state-of-the-art facility. A future construction project must be carefully prepared, and this development work is delivered through this Pre-Construction project. The proposed UK contribution to XLZD includes major experimental hardware systems, especially those most naturally suited to the host nation; these will be designed and prepared in this phase. In addition, we will deliver with key industrial partners bold programmes for clean underground manufacturing, for engineering and skills development, and for environmental sustainability. These programmes relate to challenges that must be addressed, but which we deliberately develop into opportunities: to provide return to UK industry and wider economic impact, to develop capabilities that support future STFC and UKRI projects, and to be a pathfinder in how Big Science moves towards Net Zero.

UKRI Gateway to Research · FY 2024 · 2024-06

Characterising the drivers of biological form over geological time continues to represent one of the grand challenges in evolutionary biology. However, doing so has proved difficult as there are few study systems where it is possible to test the competing roles of selection, constraint and chance. Land plants offer a largely overlooked but ideal study system for tackling these questions because of their excellent fossil record and close relationship between form, function and development. In WhyFib I will leverage all of these benefits to uncover the evolutionary drivers behind one of the key features of land plants, the arrangement of leaves. On theoretical grounds, plant leaves could be positioned on stems in an almost infinite number of possible arrangements. However, they are not. In fact, they are arranged in a very restricted number of discrete patterns, of which by far the most frequent are spirals that are described by integers of the Fibonacci series. Why Fibonacci spirals are so frequent in plants has perplexed scientists for centuries and remains a major unanswered question. In WhyFib I will answer this question by taking a broad evolutionary approach, underpinned by my own interdisciplinary background and new break-through methodologies developed in my lab. To uncover the evolutionary history of Fibonacci spirals I will combine results gained from investigating development in non-seed plants with insights from newly collected fossils, analyses of quantitative trait evolution and quantitative modelling approaches. I will then use these data, representing over 400 million years of evolution, to test the major competing hypotheses for the prevalence of Fibonacci spirals. The results of the project will provide a textbook case study for the drivers of biological form over geological time, while allowing me to solve the mystery of why Fibonacci spirals are so common in plants today.

UKRI Gateway to Research · FY 2024 · 2024-06

A consortium of the Universities of Edinburgh, Exeter, Strathclyde and Swansea supported by the Scottish Association for Marine Science (SAMS) will run the Industrial Centre for Doctoral Training for Offshore Renewable Energy (IDCORE). This partnership offers a unique combination of experience in research, development and knowledge-exchange with major industry stakeholders in the Offshore Renewable Energy (ORE) sector. This is complemented by the extensive experience with ORE projects of both SAMS, in the environmental and societal impacts, and the Fraser of Allander Institute (Strathclyde), in macro- and micro-economics. The large scale deployment of ORE technologies is key to the UK achieving its net-zero carbon energy objectives while, at the same time, delivering secure, reliable and affordable energy. Both of these objectives must be achieved with minimal environmental impact. This requires the continuing development of new techniques and technologies to design, build, install, operate, and maintain energy generating machines in a hostile marine environment. Successful ORE projects must be affordable and minimise their environmental impact. Success will create green jobs at all levels in coastal communities across the UK and generate significant economic impact. The ORE sector, which includes companies ranging from world-leading technology development SMEs (like Orbital Marine Energy and MOcean Energy) through to international energy companies as well as engineering majors, consulting engineers and project developers, is creating a massive demand for highly trained scientists and engineers with a broad skill base. The consortium is ideally-placed to support the industry in meeting these challenges through a conjoined infrastructure, which begins in some of the best academic research centres with leading test facilities and extends through a unique combination of demonstration facilities, ultimately to test and deployment sites. IDCORE will conduct internationally leading research, provide a vibrant training environment and deliver a body of high-quality post-doctoral staff for the sector. This proposal presents a revised training programme in response to changes in the sector (particularly the rapid growth of offshore wind, the commercialisation of tidal stream energy, and the drive to develop floating wind systems for deeper water). It also includes Swansea University for the first time, strengthening our links to developments in the Celtic Sea and bringing significant expertise in computational modelling and aerodynamics. IDCORE provides a solid background in professional, technical and transferable skills to a diverse cohort of students drawn from a wide variety of STEM backgrounds. It is designed to deliver a tightly-knit cohort of highly-skilled graduates, forming a strong foundation for the future development of the sector. Our training is innovative and multi-disciplinary, using a variety of delivery methods and unique facilities, including: the Kelvin hydrodynamics lab, FastBlade, the FloWave Ocean Energy Research Facility, offshore measurement systems (Wave and ADCP measurement array and surveying), the South West Mooring Test Facility, accelerated fatigue testing facilities (DMAC), survey vessels and field study areas. Through established links with partner organisations including the ORE Catapult and the European Marine Energy Centre (EMEC), students will be placed and, wherever possible, site-trained in large-scale test facilities, prototype demonstration and small-farm demonstration sites. The training will also benefit from the extensive experience of the consortium in advanced engineering analysis and simulation, and access to UK-leading computational facilities. The training package offered by the centre provides our students with unparalleled engineering experience in applied offshore renewable energy R&D.

UKRI Gateway to Research · FY 2024 · 2024-06

Nonlinear dispersive partial differential equations (PDEs), such as the nonlinear wave equations (NLW), appear ubiquitously as models describing wave propagation in various branches of physics and engineering. In particular, it is well known that the one-dimensional wave equation describes the motion of a vibrating string. In a physical setting, such a vibrating string is susceptible to external forcing which is often random. Such a random external forcing is well approximated by a white noise in many situations. For this reason, it is of fundamental physical importance to study the stochastic NLW forced by space-time white noise. At the same time, such a problem also poses significant analytical challenges due to the irregularity of the space-time white noise. The main aim of this proposal is to advance our theoretical understanding of the one-dimensional stochastic NLW with multiplicative space-time white noise forcing by working on concrete examples of challenging open problems. The main difficulty of mathematical analysis on singular stochastic PDEs with white noise forcing comes from the irregularity of the white noise. Over the last decade, we have seen a tremendous progress in the study of singular stochastic PDEs with white noise forcing. In the parabolic setting, this development was led by a 2014 Fields medalist, Hairer (EPFL, Switzerland), and by Gubinelli (Oxford). Over the last five years, the principal investigator (PI) has made a substantial, world-leading contribution to the development of our theoretical understanding of singular stochastic NLW. In the proposed projects, the PI will study several important models of one-dimensional stochastic NLW with multiplicative space-time white noise forcing and aims to resolve challenging open problems by establishing their pathwise well-posedness. The PI plans to achieve this goal by developing an entirely new analytical framework which allows him to handle singular multiplicative noises in a pathwise manner.

UKRI Gateway to Research · FY 2024 · 2024-06

The construction industry is seeking to address its carbon emissions by using more sustainable, low-carbon building materials and systems. One method of construction that is becoming increasingly common is Cross Laminated Timber (CLT). This product allows huge slabs (and walls) of timber to be created by gluing lots of individual (smaller) planks together. One challenge with this way of building is that timber (unlike brick, stone, steel or concrete) burns. Exposed timber ceilings are very common in CLT buildings. Where there is exposed timber, there is always the possibility for increased fire spread. This generates a significant risk that the resulting fire dynamics could violate many underpinning assumptions of existing measures to provide adequate fire safety in buildings, and thus requires investigation. This research will study the ignition and burning of exposed timber ceilings. The research team will study this by burning timber at small scale (~10 cm wide samples) to study how the timber ignites and how the flame then heats its environment. The team will then scale up to study how one piece of burning timber, can ignite another (adjacent) piece of timber. Finally, the team will ignite fires in ~1m wide timber rooms and study how the fire spreads. The novelty of this research will be the focus on exposed timber ceilings, which as particular importance for commercial timber buildings. Much of the existing knowledge about burning timber has been generated when the timber is in the "floor" or "wall" condition. The technical challenge is in linking together the small scale experiments with the "room scale" fires. The work will be undertaken using existing facilities at the University of Edinburgh's Rushbrook Fire Laboratory. The research will take advantage of the existing depth of knowledge that the University of Edinburgh already have in this area and will help to enable the safe use of this form of construction in the UK's construction industry.

UKRI Gateway to Research · FY 2024 · 2024-06

The ability to extract target chemicals from biological samples is essential for a wide range of laboratory activities, from discovery of fundamental biological processes and biosynthetic pathways, to optimisation of strains and culture conditions for the biomanufacturing of high-value chemical products. There are two contexts in which chemicals are extracted in bioscience research: From end point samples. This is typically performed using liquid-liquid extraction. This is time-consuming and involves large volumes of hazardous solvents (often derived from finite, petrochemical sources), which must be handled within a fume hood, and which require specialist disposal. Throughout biomanufacturing processes. This continuous extraction can solve some issues like the loss of volatile products, and mitigate the toxic impact of products to microbial cell factories. It is typically achieved using an overlay of an immiscible liquid at 10 % culture volume, into which products accumulate. However, this approach brings its own issues, including concerns over foaming emulsions, solvent flammability, incompatibility with silicone-based tubing at scale-up, and the presence of contaminants. More rapid and sustainable methods of chemical extraction are urgently needed, and would present a step-change for discovery bioscience and bioprocess development. Cyclodextrins are hollow cone-shaped polymers of sugar, which can capture appropriately sized chemicals. This proof-of-principle study will produce and then demonstrate a transformative cyclodextrin-based technology for chemical extraction in the biosciences, which is rapid, low-cost and sustainable, with minimal use of petrochemical-derived solvents. The technology can be used at both small and large scale, meaning that laboratory bioprocesses can be more easily replicated at industrial volumes. The technology will be demonstrated both for end point chemical extraction from microbial cells, and for product capture throughout two exemplar biomanufacturing processes; flavour/fragrance vanillin from engineered bacteria, and an anti-cancer pharmaceutical from engineered yeast. The project will generate a wealth of knowledge, tools and resources, benefiting broad communities of academics in discovery bioscience, bioprocessing, microbe engineering, and natural product and cyclodextrin chemistry. It has the potential to transform chemical extraction in discovery bioscience and beyond, offering a more sustainable, scalable and efficient process. The project is particularly timely considering the global priority to develop net zero processes, and the recent expansion in research on the genetic engineering of microbes for chemical biomanufacturing. This proof-of-principle data will provide the basis of future interdisciplinary research, collaboration and enterprise, with commercialisation opportunities explored in collaboration with the UoE commercialisation service Edinburgh Innovations.

Fonds de recherche du Québec – Santé · FY 2023-2024 · 2023-04

Volet: Formation postdoctorale - Citoyens canadiens et résidents permanents; Domaine: Services de santé; Objet: Santé mentale et société; Objet: Services de santé; Application: Santé; Application: Gestion du système de santé; Mots-clés: SERVICES DE PSYCHIATRIE LEGALE, EVALUATION DE MODELES DE SOINS, TRAJECTOIRES DE SERVICES, METHODES MIXTES, EVALUATION REALISTE, ETUDE DE CAS INTERNATIONALE

Fonds de recherche du Québec – Société et culture · FY 2023-2024 · 2023-04

Volet: Bourses de doctorat en recherche; Domaine: Nature, transformation et gouvernance de la société et des institutions; Objet: Écologie humaine et sociale; Objet: Réseaux sociaux; Mots-clés: CAPITALISM, CLIMATE CRISIS, SOCIAL NETWORKS, HISTORICAL SOCIOLOGY, NATIONALISM, CLIMATE POLITICS

Fonds de recherche du Québec – Société et culture · FY 2023-2024 · 2023-04

Volet: Bourses postdoctorales; Domaine: Nature, transformation et gouvernance de la société et des institutions; Objet: Partis politiques; Objet: Identités régionales; Application: Politique; Application: Affaires intérieures; Mots-clés: PARTIS POLITIQUES , MOUVEMENTS SOCIAUX , NATIONALISME, HOMONATIONALISME , ENJEUX LGBTQ+, POLITIQUE QUEBECOISE ET ECOSSAISE

Other NSERC · FY 2024

Economic geology, Geochemistry, Precious and critical metals, Sulfur isotopes, Volcanogenic massive sulfides, Geochronology, Caledonides/Appalachians, Magmatic evolution, Fluid-rock reactions, Green technologies

Other NSERC · FY 2024

Urbanization, Climate change, Phenology, Trophic mismatch, Phenotypic plasticity, Phenotypic optimum, Lay date, Bud burst, Mega-analysis