University of Liverpool

UKRI Gateway to Research · FY 2024 · 2024-09

The problem of reactive synthesis asks for the automated construction of systems that adhere to input logical specifications. In practice, it is commonly solved by a reduction to games that involves the determinisation of automata that encode the input specification. We will develop methods for avoiding the obstacles that slow down this process, proceeding in two orthogonal directions: We will identify concrete special cases in which history determinism can be used in place of full determinism in the reduction to games, leading to asymptotically faster synthesis algorithms for the identified special cases. We will pay special attention to obtaining syntactic characterisations of these special cases, ensuring that they can be efficiently recognised. We will also generalise existing game reduction methods by using succinct Emerson-Lei objectives in the resulting games rather than parity ones; by evaluating approximations to solutions of these games by means of lazy algorithms; by providing efficient back-end algorithms for quantitative (multi-valued) synthesis; and finally by lifting quasipolynomial worst-case guarantees from parity objectives to the general case of quantitative Emerson-Lei objectives. Since these advancements in both directions aim at improved practical performance, we will also evaluate the developed algorithms and automata transformations with a prototypical implementation that will be benchmarked against existing hard example instances of the synthesis problem, comparing its performance with the currently leading tools (where they exist) and determine the scope and limitation of our results.

UKRI Gateway to Research · FY 2024 · 2024-08

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 · 2024-08

Most of the time our bodies' immune system operate with the brake on. This is crucial for self-tolerance and stops our cells being attacked indiscriminately. However, cancer cells can generate novel molecules which are recognised by our immune system. Revving up the immune response in this context can be highly beneficial and this concept underpins what is now known as immunotherapy. Here, the immune system is let off the leash to fight the cancer, by removing the normal braking system. The therapies that have been developed are antibodies which recognise cell surface receptors and block their interactions. One of these receptors, called CTLA4, has a fleeting existence; after being made in the cell it will be gone within the hour. It is consigned to the cell's "rubbish dump" or "lysosome", to be recycled for parts. Short-lived proteins, such as CTLA4, are normally recognised by other proteins which label them with a degradation tag or "signal" called ubiquitin. The identity of the protein that adds a ubiquitin tag onto CTLA4 and condemns it to be destroyed is unknown. We plan to discover it by sifting through about 600 candidates in a highly parallel fashion. Alongside identifying this key molecule, we will also seek to understand any nuances of the CTLA4-ubiquitin signal and identify the molecules that recognise it and usher CTLA4 to the lysosome. By understanding this basic cellular machinery that controls cellular CTLA4 levels we aim to open up new strategies for their adjustment in a therapeutically meaningful way.

UKRI Gateway to Research · FY 2024 · 2024-08

This project aims at the development of innovative green ultrasonic manufacturing technology for the production of 100% biodegradable, compostable, and 100% biobased thermoplastics using agricultural and biofuel refinery side products containing hemicelluloses (xylan), biobased 2,5-furandicarbonic acid and monoethylene glycol. These biomass-based thermoplastics (PEF) can replace petroleum-based packaging materials, fibers and commodity plastics (PET, PS, PE/PP) - the major sources of the ocean and landfill contamination with poorly recyclable microplastic particles. Approximately only 9% of petroleum-based plastic waste is recycled Worldwide. We focus on 100% degradation of the proposed thermoplastics after one-two month of composting. Ultrasonic synthesis is a green method of energy input into reaction mixture for fabrication of new types of materials in nonequilibrium conditions employing cavitation effect. It does not require additional reagents and high temperatures thus reducing the amount of by-products. We will study in-situ cavitation effects and mechanisms of the formation of biomass based thermoplastics. Application of ultrasound as a new manufacturing process for fabrication of biomass-based thermoplastics can result in 3-4 fold reduction of the energy consumption as well as CO2 footprint and minimisation of the amount of waste during manufacturing.

UKRI Gateway to Research · FY 2024 · 2024-08

This research project enquires into the value of Indigenous contemporary art practice as a tool for inquiry on water and a means for understanding contemporary ecological challenges. While much has been written about water as a concept and object of inquiry for examining the relationship between water and society in the social sciences and humanities, and Indigenous artists have engaged with water and changing environments in their methodological practice, these have frequently been parallel conversations. The urgent need for interdisciplinary thinking provides an opportunity for collaboration with contemporary Indigenous artists, curators and cultural institutions to critically rethink water as a concept in institutional settings, and how it is deployed and investigated in the production of knowledge. Understanding water in Indigenous artistic practice pushes back against the essentialist view of common water to address a plurality of approaches that respond to changing environments. This project will address that need by bringing into dialogue methodological engagements with water in Indigenous cultural production within art institutions together with social scientists and scientists for rethinking water and the power of art in challenging and transforming the concept of water from an indigenous perspective. The two workshops that form part of this project contribute to an interdisciplinary dialogue by providing an opportunity to engage with First people's connections to water, and investigate the methodologies, practices and methods of storytelling deployed by Indigenous artists, and professional curators and community organizations. The workshops reflect on the international Indigenous connections to water in the exhibition Naadohbii: to draw water which took place in Winnipeg (August 2021- February 2022) and Melbourne (September 2022 - December 2022) and brought together 28 Indigenous artists from Canada, Australia and New Zealand. Investigating global Indigenous engagements with water in the Canadian and Antipodean contexts and how contemporary artists methods and artistic concepts may overlap or differ from each other, opens up the question of what water is and the role it plays in methodological practice for engaging artists, academic and non-academic professional, publics, and enacting change.

UKRI Gateway to Research · FY 2024 · 2024-08

John Garstang (1876-1956) was one of the most prolific excavators of his day, digging at sites along the Egyptian and Sudanese Nile, Syria, Palestine and Turkey. Garstang was trained in the field by the most prominent excavator of the time, Flinders Petrie (1853-1942) of University College London, but soon moved on to run his own excavations, establishing the Institute of Archaeology in Liverpool (1904). Between 1884 and 1983 the Egyptian Antiquities Service could grant excavators a division of the finds made each season, reserving the most significant objects for the Egyptian Museum in Cairo. Garstang's excavations were sponsored by a committee of patrons who received a share of the finds exported under the terms of the excavation permit. Museums in the UK and worldwide benefited and other objects found their way onto the auction market, creating a widespread distribution that has yet to be recorded. This distribution (c.100 institutions) has restricted findability, accessibility, and usage. Some Garstang excavation finds and archives provide the only record of communities and landscapes that have been destroyed (e.g. Meroë in Sudan), but material is not accessioned/ catalogued. In many repositories, replicas and reference materials are confused with originals. Important objects are stored across repositories with vastly diverse research and discovery infrastructure and particularly for small museums (with a concentration in the North West), there are limited resources and no subject expertise to identify finds or reinterpret holdings. Some holdings surveys have been carried out to aid research, but whilst it remains difficult to trace a corpus of material, the Garstang collection is off the radar for multidisciplinary research purposes. This compounds a London-centric concentration of use and reuse of archaeological collections for heritage science. The largest holdings of Garstang finds and archives are held across the University of Liverpool (UoL) Garstang Museum of Archaeology, and National Museums Liverpool (NML), with approximately 50% accessioned and limited data online. Liverpool has world class experts, archaeology laboratories and digital heritage facilities offering a unique ecosystem alongside the Garstang Museum, all working as complementary enablers and connectors for heritage science research. We will transform accessibility and visibility of the distributed collection with a network of partner museums and expertise starting in the North West, with the intention to go global. We will simplify the research process, creating opportunities for academic researchers to work with collection finds in repositories that have not had recognition or visibility as research infrastructure. Researchers and curators will enhance knowledge and understanding of material composition, deepen understanding of colonial acquisition and distribution practices, working with countries of origin. Researchers will be able to investigate lost landscapes and cultures, particularly pertinent for regions with political instability. This will be achieved by: improving collection security and storage at UoL, enabling multiple stakeholders and experts to access and document the collection safely; creating virtual consultation environments using visualisers for collaborative conversations and identification of Garstang finds; adopting a comprehensive collections management system, collating records of UoL finds and data extracted from archival records and photographs, creating an online portal to publicise and track research resources across institutions and share expert digital interpretation and visualisations, including Arabic access points; create an ongoing community network of repositories to improve public understanding and usability in research, building evidence of distribution and finds information, sharing best practice in distributed collections accessibility.

UKRI Gateway to Research · FY 2024 · 2024-08

Satellites and other airborne sensors create remarkable forms of smart data, with enormous untapped potential to transform research and policymaking across social science and health domains. Satellite imagery not only contains highly relevant information about places—how well off they are, how quickly they are developing and where, and available types of green, blue, and urban spaces—but also possesses other distinctive qualities. It is comprehensive and representative, with wide geographic coverage and regular updates, robust to many types of bias, and offers unique retrospective power, facilitating understanding of how a place is today, as well as how it has changed over previous years. At the same time, there is a critical dearth of data, where sustainability, prosperity, and wellbeing are concerned, especially for understanding and resolving persistent social and economic spatial inequalities, the impacts of environmental changes on people and places, and uneven outcomes in health and life expectancy. Satellite imagery offers a game-changing solution. However, given its technical complexity and requirements for specialist knowledge, to date it has mostly been leveraged by environmental scientists and engineers. IMAGO seeks a complete disruption of the status quo, proposing an SDR UK Data Service that transforms the usability, utility, and usage of satellite imagery that, in turn, revolutionises our understanding and resolution of urgent challenges facing the UK—especially where environmental vulnerability, urban development and housing, and health and wellbeing are concerned. IMAGO achieves its goal by meeting users where they are: translating complex imagery data into data products these stakeholders require through collaboration and co-production; delivering data via intuitive and user-friendly interfaces, as well as channels, formats, and approaches familiar to these communities; and expanding capacity and enthusiasm for using imagery-based data across a range of sectors, career stages, and disciplines. We adopt a highly innovative approach to achieve our vision, working across three principal aims. First: combining the development of novel computing and AI methods and stakeholder collaboration to co-develop automated workflows and data products at scale for custom-defined geographies and time periods (for example, quarterly counts of solar panel roofs for Newcastle postcodes, between 2015-2022). Second, data distribution channels that leverage the power of existing investments (e.g., Understanding Society, other SDR UK data services, NCEO's Data Hub, NERC Digital Solutions), alongside a user-friendly interface featuring interactive mapping, Large Language Model (LLM) powered data discovery and summarisation, and clear metadata and documentation. Third, high-visibility training and research activity, including in-house collaborative Beacon Research, to catalyse the adoption of satellite imagery for social science and health research and policymaking. Attention to ethics, public engagement, and continuous evaluation will underpin all IMAGO activities. Partnerships are key to delivering IMAGO, as barriers to imagery's uptake for research, policy, and practice in the social sciences and health are only partly resolved with data partnerships that enhance access. A second key limitation has been complexity and format of imagery data. To overcome this limitation and guarantee data are used, IMAGO works with data distribution partners, embedding linkage and flexibility. Third, bridging the gap between imagery's potential and actual usefulness, IMAGO works with application partners to establish data requirements, co-develop and promote data products, and collaborate on, and disseminate, impactful research and policy. IMAGO starts with an inaugural set of agreed partners, with an ambitious expansion plan as the data service grows.

UKRI Gateway to Research · FY 2024 · 2024-08

Autism, or Autistic Spectrum Disorder (ASD), is a lifelong developmental disability which affects how people communicate and interact with the world. It affects around 3% of children. Children with ASD experience cognitive, sensory, and social challenges, including in schools. They face adverse health and education outcomes, such as an increased risk of cognitive development delays, motor skill challenges, anxiety, and school absence and exclusion. The lifetime cost of supporting an individual with ASD in the UK was £0.92 million in 2011, whilst annual special education and health-related costs for 4-17-year-olds with ASD were £14,006 and £890. Clinical assessments for ASD are typically conducted within Child and Adolescent Mental Health Services (CAMHS), and a formal diagnosis is a crucial step toward accessing tailored support and services addressing the unique challenges of ASD. Although there is some opportunity for additional support in schools without a clinical diagnosis, many children with autism are not getting the full support they need. There is a significant challenge within the current clinical system for assessing ASD. Waiting times for assessments have surpassed 5 years in some regions, creating an unmanageable backlog. This crisis necessitates immediate action to ensure timely support for children in both health and education settings. To address this pressing issue, this project will generate new knowledge about the impact of clinical diagnosis of ASD upon inequalities in health and education outcomes for children in England. This knowledge will enable health and education services to identify opportunities to intervene to mitigate inequalities. I will analyse data from Education and Child Health Insights from Linked Data (ECHILD). ECHILD joins together health, education and social care information for all children in England and provides a detailed picture of outcomes. The project will draw upon diverse disciplines such as public health, data science, and geography to explore health and educational outcomes for autistic children, considering the broader context of service shortages in clinical assessments. The primary goal is to investigate whether obtaining a diagnosis from a clinical setting offers additional advantages to children identified solely in an educational setting with ASD, who may require extra support. This exploration aims to enhance our understanding of which children would benefit most from clinical diagnoses. The insights gained could be applied to prioritising children on waiting lists, introducing fair and programmable practices into health systems. The benefit is that the needs of children could be better matched by the services that support them. The project's practical relevance lies in directly addressing challenges related to underdiagnosis and the crisis in clinical services. It strives to promote equal care for children, particularly those from disadvantaged backgrounds who may face exacerbated disadvantages if their ASD is not identified and addressed. I am committed to working closely with key stakeholders, including members of education and health services supporting autistic children, as well as involving members of the ASD community. The potential impact of this project is substantial, with the capacity to bring about tangible education and health benefits and create meaningful impact. It addresses the crisis currently faced by frontline practitioners, policymakers, and other stakeholders striving to support autistic children. The proposal aligns with the objectives of fostering engagement and community building in administrative data research, emphasising a dedication to making a positive difference in the lives of autistic children and their families.

UKRI Gateway to Research · FY 2024 · 2024-08

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 · 2024-08

Our project, DEBIAS, aims to develop a generalisable framework to quantify and adjust existing biases in Digital Footprint Data (DFD) on human mobility. To this end, we will use DFD on human mobility obtained from users of the social media platforms Facebook and X (previously Twitter), and from smartphone applications collected by the company Huq. We will use data from the UK, but our framework will be reproducible and transferable to any DF source and geographical setting. Our framework will rely on aggregate human mobility data capturing flows of people between origins and destinations. Key benefits of using this data structure are that these data are more easily accessible. They help overcome ethical concerns ensuring anonymisation and represent a common format used by data providers to share DFD on mobility. Why mobility? Understanding how humans move is key to supporting appropriate policy responses to address population issues, carbon emission, urban planning, service delivery, public health and disaster management. DFD, such as location data collected from smartphone apps offer a unique opportunity to analyse population movements at high geographic and temporal granularity, with extensive coverage in near real-time. Research leveraging DFD has have a transformative impact expanding existing theories and developing new analytical tools and infrastructure of social and spatial human behaviour across the social sciences. Challenge: Biases in DFD have represented a major methodological barrier to reaping their benefits, contributing to scepticism and deterring wider usage of DFD. Biases mainly exist due to differences in: 1) the access and usage of the digital technologies used to collect the data (e.g. only 70% of the British population uses Facebook); and, 2) the demographic and socioeconomic profiles of users of the technology (e.g. Twitter has a young adult and male-dominated user profile mainly from urban areas). As such, human mobility data derived from DFD offer a partial representation of the overall population, limiting our capacity to draw conclusions about the overall local population. Promise: DEBIAS will deliver a framework to adjust biases in DF-derived mobility data and an open-source software package and training materials to implement it. These outcomes will contribute to delivering the Smart Data Research UK (SDRUK) programme aim of unlocking the power of new forms of data for research and innovation to tackle social challenges by 1) enabling the monitorisation and prediction of patterns of human mobility by facilitating robust real-time analysis based on DFs; 2) augmenting the technical social science research capacity in the use of DFD; 3) expanding existing theories and developing new explanations on spatial human behaviour by supporting research on highly granular space-time mobility patterns; and, 4) supporting the long-term access to robust and ethical DF-derived mobility data. DEBIAS will thus contribute to SDRUK-specific objectives by providing secure data access, safeguarding public trust, and building capability for cutting-edge research. To maximise impact, we will engage with direct beneficiaries of our work: a) researchers and analysts; b) public sector agencies; and, c) commercial stakeholders or third sector organisations engaged in data for public good initiatives and working in mobility, transport and migration. We will establish an advisory board representing expertise from the commercial (Meta), academic (Northeastern U.) and transgovernmental (UN) sectors, to inform the development of our software tool and training materials. Working with Meta and UN-IOM will enable the exploration of opportunities for long-term strategic partnerships for data access and application of our approach to new problems. We will disseminate and increase the awareness of our work via research articles, presentations and workshops targeting different audiences and adopting open science principles.

UKRI Gateway to Research · FY 2024 · 2024-08

Inner-city Johannesburg, in South Africa, mirrors the complex health challenges of middle-income countries. The appeal of city life has led to mass migration to urban areas where people face overcrowding, noise, pollution, crime, drugs, unemployment and other issues. Urban food options and offerings such as the availability of cheap, fast, processed food, along with modern, more sedentary lifestyles, is contributing to an unfolding obesity epidemic. South Africa's ongoing success with the HIV epidemic means the disease is now largely controlled by freely accessible drugs and care. To tackle HIV, South Africa developed and adopted new practices and approaches, not just treating HIV with drugs, but finding those who did not know they were sick, and linking them to health services. This is done in ways that enable patients to get the medicine and care needed but also to understand their condition, how they can help manage it to stay healthy, and what other services they are entitled to. We aim to use what we have learnt to find people with chronic diseases caused by lifestyle changes, especially undiagnosed and untreated high blood pressure and diabetes, which now account for most treatable deaths in South Africa. Many workplaces in the inner city are close to clinics and GPs, providing opportunities to link sick employees to healthcare quickly and easily. We will set up a health screening programme for city workplaces and design a friendly, innovative employee programme to screen for diseases like diabetes and high blood pressure and assist people to link to care at local health clinics. We will design an engaging, inner-city specific healthy food education programme to introduce people to other food choices including where to buy affordable healthy food nearby. The project will be designed by researchers from the University of Liverpool, the University of Witwatersrand in Johannesburg and local employees, managers, community groups, and charitable organisations involved in food activism, including diabetic groups and people involved in public health programmes and medical insurance: all groups with a stake in making screening successful. We aim to get a good understanding of the motivations related to health screening, health seeking and food consumption behaviours in order to be able to address it in an effective way to help people become and stay healthy. We will test the programme in workplaces to see what works and what needs improving, and cost our activities to ensure they are affordable. We will then make recommendations on our findings to policy makers, donors, governments and funders. If our project can find ways to better understand high blood pressure, diabetes and possibly obesity epidemics, using approaches that worked for HIV, we will have begun the process of tackling the challenge of complex lifestyle conditions which in future is likely to include other challenges like mental illness, chronic lung disease and sleep disorders.

UKRI Gateway to Research · FY 2024 · 2024-08

The burden of antimicrobial resistance (AMR) is increasing. AMR-associated global mortality is predicted to reach 10 million annually.1-3 Despite most antimicrobial use occurring in community settings,2 few community-appropriate antimicrobials are in development. Thus, optimising the use of existing antimicrobials to maintain their efficacy and prevent AMR progression is essential.4,5 Pneumococcus is the causative bacterium for many community infections and has World Health Organisation (WHO) priority status.2,5 Amoxicillin is a first-choice antimicrobial for pneumococcal infections.2 Amoxicillin and amoxicillin/clavulanic acid are the most frequently used antimicrobials globally, including in the United Kingdom.6,7 Despite extensive global use, understanding of the best way to administer amoxicillin in terms of dose, schedule, and treatment duration (i.e., the regimen) to achieve clinical cure and simultaneously minimise AMR emergence remains limited, and this has implications for global health policy. Challenges: Two distinct events are likely relevant for pneumococcal emergence of resistance to amoxicillin: (i) an initial transformation event whereby there is uptake of resistance genes - importantly, this phenomenon does not require amoxicillin;8-10 and, (ii) subsequent selection and expansion of resistant clones under amoxicillin pressure.11 The ambient conditions required for both events are poorly understood. The factors that make pneumococcus more likely to take up DNA are uncertain. Although the ultimate mechanism of pneumococcal amoxicillin resistance is well established, molecular pathways to that endpoint are ill-defined, compromising the design of mitigation strategies. Once generated, the selection and expansion of resistant clones depends on exposure to amoxicillin within sites of colonisation and infection. Antimicrobials may not readily partition to some infection sites (collectively termed "sequestered disease"). The impact of spatial variation in antimicrobial exposure on response and resistance liabilities is unknown. Addressing these knowledge gaps will help identify optimal amoxicillin regimens that maximise antimicrobial activity for different infections, while minimising the emergence of resistance. Given the frequency of pneumococcal disease and decades of amoxicillin use, extensive anatomical, microbiological, and pharmacological data are available. In isolation, neither these data nor traditional clinical studies can be readily used to predict the resistance liabilities of amoxicillin. Quantitative systems pharmacology is a potential computational method of integrating existing data, incorporating new findings, generating hypotheses to direct future clinical/experimental research, and identifying optimal amoxicillin regimens for global use.

UKRI Gateway to Research · FY 2024 · 2024-08

The 2024 Northern Ireland General Election study will provide a comprehensive analysis of why Northern Ireland's electors voted the way they did (or did not vote). It will facilitate a detailed statistical analysis of the extent of political divisions within Northern Ireland; allow consideration of whether its faultlines are deepening and offer evidence as how they might be healed. The study will be based upon a post-election survey of a representative sample (weighted by age, religious community background, social class and area (90 wards across the Northern Ireland's 18 parliamentary constituencies) of 2,000 electors across Northern Ireland. The survey will be based upon face-to-face interviews with electors and completed within three months following the date of the general election. It will be complemented by focus group discussion with various categories of electors. The bid is based upon a mid-October election (latest possible date is January 2025) but constructed flexibly to allow for an earlier call. This will be an important examination of the views of the Northern Ireland electorate during a period of political upheaval and difficulty Whilst the survey allows comparisons with the British Election Survey, covering England, Scotland and Wales, a sizeable element will be Northern Ireland-specific to reflect unique political circumstances. The election comes amid political upheaval. Sinn Féin has become the largest party in the Northern Ireland Assembly and local government, displacing the Democratic Unionist Party (DUP). The non-unionist and non-nationalist Alliance Party has become the third largest party. Sinn Féin's ascent to largest party status has increased calls for a referendum (border poll) on Northern Ireland's constitutional status. Meanwhile, the Northern Ireland Assembly and power-sharing Executive have been collapsed since Spring 2022, when the largest unionist party, the DUP, quit in protest over the EU Ireland/Northern Ireland Protocol (subsequently Windsor Framework) operating as the post-Brexit UK-Ireland/EU trading arrangement for Northern Ireland. The institutions were previously collapsed from January 2017 to January 2020, across the last two general elections, after Sinn Féin quit the power-sharing Executive, mainly over claims of DUP mismanagement and the absence of an Irish Language Act. The Secretary of State for Northern Ireland has legislated across several areas, including budgets, abortion, same-sex marriage and Irish language, following these institutional collapses. The survey will obtain the views on electors across the following areas; why they voted or did not vote; the basis of party choice and how it compares to previous Westminster, Assembly and local elections; attitudes towards other political parties; attitudes towards devolved power-sharing; views on Northern Ireland's political institutions; should they remain and if so, should they be reformed and how? support for - or opposition to - the Windsor Framework as the post-Brexit trading arrangement for Northern Ireland perceptions of the likelihood of a border poll constitutional choice regarding support for Northern Ireland remaining in the UK or becoming part of a united Ireland. The core aim of the study is to provide a robust examination of the attitudes of Northern Ireland's electors at the general election across the key issues at that contest. This is important not only as a snapshot but as part of longitudinal data (the PI applicant has directed the previous four general election studies) allowing researchers access to data which provides a clear guide to the extent of change or immobilism in Northern Irish politics.

UKRI Gateway to Research · FY 2024 · 2024-07

Context: The capacity of sequencing machines has massively increased, with the construction of sequencing libraries unable to keep pace. This application requests equipment to implement an advanced robotic liquid handling pipeline that can generate NGS libraries at four times the throughput and a quarter of the cost of current approaches. The pipeline will be situated within the Centre for Genomics Research (CGR), a faculty research facility at the University of Liverpool, which provides world-leading expertise and infrastructure to the UK scientific community. Removing the library preparation bottleneck will be transformative, unlocking new questions within BBSRC remit and allowing analysis of experiments and collections at a scale hitherto only available for human studies. Research Enabled by Equipment: At the CGR we specialise in sequencing non-human genomes and exploring experimental genome biology. The acquisition of robotic liquid handling equipment will revolutionise sequencing library construction of RNAseq, DNA shotgun and amplicon projects. This will increase throughput, reduce costs, and enable more complex genomic studies. This will enable population-level studies of 1000s of samples. We will embed capability through a suite of exemplar projects relevant to BBSRC in digital dermatitis in dairy cattle, plant-bacterial and plant-insect interactions in barley, and identify genes related to crop traits in Brassica crops. It will develop synergies within integrative microbiome research from the deployment of population-scale genomics across different microbiome systems. Our open-access approach means that we will support Cira. 200 projects per annum will support a broad user base, national and international, that includes PhD students, ECRs and established PIs. Aims and Objectives: The primary aim is to support more robust and reproducible science by advancing significantly better experimental designs using population-scale genomics for non-human systems. The objective is to develop and deliver three protocols on the new pipeline within eight months of funding. That will provide high-quality, cost-effective genomic research. Addressing the growing demand within the research community and supporting a wide range of genomic studies. Potential Applications and Benefits: The equipment will benefit BBSRC and UKRI research, including health, agriculture, and environmental science. This work's potential applications and benefits extend beyond academic research as they will be used by industry through our partnership with Unilever and other companies in the North West of England. The new equipment will enhance national preparedness by supporting genomic surveillance of zoonotic and pandemic threats, as evidenced by previous work on SARS-CoV2 with CGR's involvement in COG-UK and wastewater surveillance initiatives. Additionally, the equipment will aid in developing Next Generation Sequencing (NGS) Diagnostics for the NHS, furthering medical research and healthcare capabilities.

UKRI Gateway to Research · FY 2024 · 2024-07

POSEIDON brings together an interdisciplinary and intersectoral team to deliver 10 professionally trained next-generation Early-Career Researchers to develop a step change in our capacity to identify, map, assess and predict offshore geohazards and in turn produce ground-breaking methods to prevent, mitigate and boost the resilience of current offshore infrastructure under a changing climate. The consortium is formed by experts across 7 EU countries with 7 universities, 2 research institutions, 4 industry partners and 1 government body to cover a full training programme on scientific and transferable skills. The programme will undertake critical research across scales (from micro to macro) for seeking the inner links and differences, with an eventual aim to ascertain the pathways and grow our capacity for the enhancement of the existing and the robust development of new offshore infrastructure in the frame of safety and resiliency. In addition to the informed design and implementation of the novel physical/numerical modelling and lab studies, our approach is unique in the solid integration and utilisation of state-of-the-art data science technologies (e.g. data mining, machine learning, etc.) to their full potential. Only through this systematic approach, we can achieve the objectives of understanding the impact of offshore geohazards on our offshore critical infrastructures and developing novel models, tools and designs for future OCIs, such as, wind turbines, pipelines and cables. The ESRs will enjoy a highly integrated, interdisciplinary and intersector training environment, enriched through secondments with the network of non-academics. POSEIDON enables critical learning across all training aspects to ensure that comprehensive, robust and implementable solutions are obtained and validated to face the OCIs climate-resilient building.

UKRI Gateway to Research · FY 2024 · 2024-07

Mitochondria are the power stations within nearly all human cells. From time to time these are decommisoned and new ones are made. The old or damaged mitochondria are delivered to the cell breakers yard or lysosome in a process called mitophagy. Mitophagy is important in developmental pathways but also in suppressing neurodegeneration and other pathophysological conditions. Sometimes mitophagy can be over-active and patients are left with too few mitochondria for the body's energy needs and suffer from mitochondrial depletion syndrome. This is the case for patients with a mutation in a gene called FBXL4. We have recently figured out how such mutations lead to this excess of mitophagy, by showing that FBXL4 controls the levels of another protein called NIX, which can dive into the mitochondria and effectively act as a notice of condemnation. Now we want to build on these findings and provide a more integrated view of the mitophagy process that looks at how the function of FBXL4 is choreographed with other proteins and modifications. Our work combines hypothesis-driven and more open-ended discovery based research which may lead to new ways of influencing mitochondrial health for the benefit of patients.

UKRI Gateway to Research · FY 2024 · 2024-07

Introduction: The objective of this proposal is to develop a high-throughput approach to understand fitness effects that individual genes in Escherichia coli genomes exert on other genes in the same genome, an essential step towards advancing our knowledge of bacterial evolution, gene function, and drug resistance mechanisms. In previous work, we have developed a machine learning model that predicts the likelihood of individual genes conferring specific fitness effects on the host genome. In this proposal, we will test the validity and accuracy of our model through empirical experimentation. An exemplar of the potential impact of this proposal is the emerging field of synthetic metabolism. Not only is synthetic metabolism of applied importance, but it also asks fundamental questions about what metabolisms are possible, beyond the subset of metabolisms and metabolic modes we observe in extant organisms. Early metabolism is thought to have evolved before nucleic acid-mediated inheritance, so can be considered the most fundamental property or layer of living systems, and understanding the rules of life requires a much more comprehensive understanding of metabolism space than we currently have. Construction of a synthetic metabolism is currently a herculean task, involving predicting and implementing many genetic modifications required for a cell to host a synthetic metabolism. In our vision, the pangenome-panmetabolism relationship will be predictable in the near future, using a combination of our modelling approach, with high-throughput model verification, enabling the exploration of the global metabolism design space to be more tractable. Methods: In preliminary work we built a machine learning model detailing importances between genes in a 2,500 genome sample of the E. coli pangenome (example data outlined in Vision Figure 1). In this model, we identified more than 3,000 communities of genes that exert influence on one another's presence or absence. The step-change objective of empirically verifying the model involves conducting high-throughput experiments using massively parallel combinatorial DNA assembly to synthetically implement and test many different permutations of 'gene communities' with informative features, chosen from our E. coli model. We will assess the impact of these community permutations on organismal fitness through growth rate measurements in large pools using deep sequencing. We will compare the experimental results with the predictions of our machine learning model. We will evaluate the model's accuracy and modify it as needed to improve its predictive power. Expected Outcomes: This research will clarify the relationship between model prediction and empirical observation. This will provide insights into the fitness effects exerted by individual genes on one another in E. coli genomes, thus answering the question of whether or not gene content can be predicted and whether genomes can be designed by this approach. The high-throughput system developed in this project will enable future investigations into fitness impacts of large numbers of genes in diverse bacterial species. Additionally, this work will contribute to the development of new methods for predicting gene function and drug resistance mechanisms.

UKRI Gateway to Research · FY 2024 · 2024-07

Astrophysical observations require the existence of dark matter (DM) to explain how visible objects like stars move in response to the gravitational pull of DM concentrations like galactic halos. DM is our best evidence for the existence of particles beyond the standard model of physics; the eventual discovery of their nature will be of profound importance. While there are some well-motivated DM candidates, intensive searches for them are as yet unsuccessful, and there is high interest in the community in also exploring for more general DM candidates. The central idea of this proposal is that dramatic improvements in the sensitivity of such searches are possible through wide-ranging theoretical efforts to help develop new experimental strategies based on emerging technologies. To realise this vision, I propose an innovative program divided into 3 work packages (WPs), each designed to attack specific blind spots in our searches for general DM candidates. These WPs are closely connected to each other, as the theoretical developments in all three areas significantly enhance the experimental capabilities of low threshold DM detection or are enabled by new data generated in new quantum simulator setups. As these WPs are developed, there is a high potential for spin-offs that benefit society. WP1: As a member of the QUEST collaboration, I will focus on improving the sensitivity of the superfluid Helium based QUEST experiment to light DM, by a precision calculation of DM accumulation in the Earth's crust, refining my earlier work [1,5,6]. WP2: I will focus on creating a computational pipeline to automatically screen for organic molecules, that will serve as a new target in cheap, scalable detectors for light DM with low interaction area. The developed pipeline will be a versatile tool for general molecule classification, that can find broader applications in protein-molecule binding optimization and drug discovery. WP3 will make use of the second research area of the QUEST experiment, which simulates an early universe phase transition as a quantum analogue system, and allows me to use my code [2,3] to predict the GW signals in heavy DM scenarios [4,9,12]. As I demonstrated in [11], those scenarios feature DM-bound states, and using my search strategy [8,10,11], combining gamma-ray experiments and GW detectors will ultimately test this challenging DM mass range. Overall, I am well positioned to carry out this ambitious, interdisciplinary project. In my career, I worked on topics ranging from physics to applied chemistry. In organizing workshops, seminars, and leading international projects, I demonstrated leadership skills. Finally, in developing and patenting (see CV) a new production method for an antibacterial composition, I gained substantial experience working with industry. This experience will enable me to strengthen collaborations with the industry and make the computational tools developed in WP2 available for broader use. My goals strongly align with UoL strategic research directions and ensure robust host-institution support for my programme. I will interact with strong local experts Prof. Coleman (MAGIS), Dr. Schaich (lattice gauge theory), Prof. Andreopoulos (Genie code), Dr. Burdin (XENON), and Prof. Greenshaw (CTA), which will be very advantageous for the investigation of DM accumulation effects, and complementary searches. To carry out the work and provide outstanding opportunities for my students and postdocs, I will take advantage of my strong international collaboration network. I will collaborate with Dr. Blanco (Princeton) who has relevant detector design experience, Dr. Leane (Stanford), Prof. Slatyer (MIT), Prof. Beacom (OSU), and Prof. Linden (Stockholm University) who are leading experts on astrophysical, and precision tests of DM. Note: Reference numbers as in CV.

UKRI Gateway to Research · FY 2024 · 2024-07

WHAT IS THE PROBLEM? Caesarean section is considered a life-saving procedure for pregnant women and their babies. Yet, in low- and middle-income countries, mothers who give birth by caesarean section are 100 times more likely to die than those having the procedure in high-income countries. In these settings, caesarean sections also contribute to life-long health problems that affect the women's quality of life and their ability to safely have more children. Their babies are also at high risk of dying during or soon after caesarean section. The three main reasons for poor outcomes after caesarean section in low- and middle-income countries are: 1. Inappropriate caesarean sections (e.g. performed 'too many, too soon' or 'too little, too late') 2. Unsafe practices in performing the procedure 3. Substandard care in labour (e.g. not culminating in vaginal birth which leads to complicated caesarean sections in advanced labour). Many issues contribute to the above problems such as lack of knowledge and skills to undertake safe caesarean section (and to achieve safe vaginal births - both normal and by using instruments). In addition, attitudes towards caesarean section and use of vacuum or forceps, marginalisation of midwives, dysfunctional teamwork, a culture of blame and medico-legal concerns, influence of family members and communities in decision-making, poor communication skills between women and healthcare providers and amongst clinicians, and inability to determine why caesarean sections are performed worsen the problem. WHAT IS NEEDED? There is no single solution to the above complex problems. We need to both improve the safety of caesarean sections and ensure they are only done when needed. To do this, we will co-develop evidence-based interventions that are acceptable, equitable, sustainable and which can be adapted or scaled-up cost-effectively across settings, by collaborating with women and their support networks, healthcare providers, policymakers and other relevant stakeholders. WHAT IS OUR AIM? We propose a 5-year Programme that aims to improve mother and baby outcomes following caesarean sections in low- and middle-income countries. The Programme (C-Safe) plans to (ii) ensure caesarean sections are done for the right reasons (C-Why), (ii) improve their safety (C-Op), and (iii) promote safe and respectful care in labour resulting in vaginal births, including safe delivery with instruments (C-Non). The C-Safe intervention will be implemented using a comprehensive training Programme, empowerment of local opinion leaders (C-Safe Champions) and mothers, team-based working, and learning through audit and feedback, in four hospitals each in India and Tanzania (30,000 births). WHAT WILL WE DO? The C-Safe Programme involves four work packages that will (i) identify and bring together evidence on the effects of interventions and outcomes, (ii) rank the interventions and outcomes according to their importance to key local professionals, local maternity care users, and community members, (iii) develop the interventions with regional healthcare providers, women and policymakers on what is considered to be beneficial, acceptable, relevant, accessible and feasible and (iv) test whether the C-Safe strategy changes practices and increases uptake of the intervention by healthcare providers, as well as the number of women receiving it. We will also assess costs and views of healthcare providers, women, their family and community members on being part of it. Building academic and training capacity and capability, and involving women and their communities in all aspects of the study, are core features. WHO ARE THE TEAM MEMBERS? The team includes doctors, , midwives, experts in study design, patient and public involvement groups, trainers, policymakers. They are supported by members of the World Health Organization, UNICEF, Jhpiego, Professional associations, ELLY Charity.

UKRI Gateway to Research · FY 2024 · 2024-07

Robot bimanual manipulation (RBM) is essential for human-like tasks in both industrial and domestic settings. Current research on RBM mainly focuses on motion planning for contactless tasks. However, it has not been well investigated yet how to handle more challenging bimanual contact-rich tasks, in which three aspects are pretty critical, i.e., the RBM skill presentation, compliant interaction, and robust generalizability. BiCoEXP targets to exceed the state-of-the-art for trustworthy contact-rich RBM by enabling robots to learn from experience and exploration, namely, learn multifeatured manipulation RBM skills from human demonstration (LfD), and then learn robust control-aware manipulation policies via deep reinforcement learning (DRL). Specifically, a skill primitive representation will be first developed to encode multiple manipulation features, including motion trajectories, impedance/force, and manipulability profiles, which can be estimated from a multimodal dataset obtained from human demonstrations. To address the coordination of dual arms, a deep neural network (DNN) model integrating a multimodal transformer-based encoder-decoder with a graph network will be developed and trained to model bimanual coordinated actions. Subsequently, a hierarchical control strategy will be designed to retrieve the learned manipulation and coordination features and to guarantee compliant and safe robot-environment interaction in contact-rich scenarios. Further, BiCoEXP will develop a multi-level control-aware DRL-based learning control framework for contact-rich RBM skills, in which the DRL agent will be enabled to learn explainable control-aware policies instead of directly outputting explicit motion/force commands. A multi-level policy mechanism will be designed to bring the benefits of high-level learning and low-level control together to achieve better robustness and stronger generalizability. BiCoEXP is expected to push this topic forward to a higher level.

UKRI Gateway to Research · FY 2024 · 2024-06

Inorganic/Organic Nanocomposite Particles (I/O-NP) are a highly versatile platform technology, currently being developed for use in diagnostic medical applications. I/O-NPs are composed of functional polymeric organic nanoscale structures (50-200 nm) in which smaller metallic nanoparticles (2-20 nm) are encapsulated. The synthetic versatility of the platform technology allows for fine tuning of the composition and architectures of the nanoscale structures, thus offering the potential for a new class of biologically responsive, functional materials to be developed. The incorporation of magnetic iron oxide nanoparticles within biologically responsive organic nanostructures would give rise to composite materials that could (a) swell or contract in response to biological stimuli or (b) accumulate around a biological target. In either case, the magnetic characteristics of the iron oxides employed would be varied as a result of changes in their rotation dynamics and interparticle proximity. Such magnetic property variation could be exploited to design detection systems, capable of detecting minute quantities of biological stimulus. As biological tissue contains no magnetic material, the versatility of the I/O-NP platform technology offers a range of potential for wide healthcare applications, providing more sensitive, specific, and quantitative diagnostic analysis, with real-time monitoring and quantification in biological systems potential with no background signal. The specific aims of this FLF renewal are towards the creation of world-leading expertise, building towards the future establishment of the Advanced Magnetic Materials for Healthcare Hub (AM4H) at UoL. The Hub will allow for a cross-disciplinary community of researchers in fields of Materials Science, Biology, Physics and Clinical Sciences to build synergies and research projects around cutting-edge technologies that are currently not present in the UK or Europe. The fellowship applicant, Dr Marco Giardiello, has built a global reputation through his cross-disciplinary collaborations and experience of inorganic and organic nanomedicine research in both diagnostic and therapeutic areas. The research programme is to be carried out at the University of Liverpool's Department of Chemistry, with critical cross-faculty, cross-sector and multi-disciplinary collaboration in place to ensure its successful outcomes as well as long-term future I/O-NP wide platform technology development. The fellowship renewal's key aims are: 1. Novel smart and biologically responsive Inorganic/Organic Nanocomposite Particle development 2. Novel device engineering and pre-clinical investigation, ensuring IP generation and industrial engagement 3. Establishment of multidisciplinary research strategies, fostering networks to set the foundation towards the creation of the Advanced Magnetic Materials for Healthcare Hub (AM4H) 4. Wide I/O-NP platform technology expansion towards multiple global healthcare needs

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

The need for the UK to shift to NetZero was highlighted at COP26 in Glasgow, and there is a clear need for UK energy security. UK policy to achieving these is based on massive expansion of off-shore wind. In 2022 Crown Estate Scotland "ScotWind" auctioned 9,000 km2 of sea space in the northern North Sea, with potential to provide almost 25 GW of offshore wind. Further developments are planned elsewhere, for example, the 300 MW Gwynt Glas Offshore Wind Farm in the Celtic Sea. These developments mark a shift in off-shore wind generation, away from shallow, well mixed coastal waters to deeper, seasonally stratified shelf seas This shift offers both challenges and opportunities which this proposal will explore. Large areas of the NW European shelf undergo seasonal thermal stratification. This annual development of a thermocline, separating warm surface water from cold deep water, is fundamental to biological productivity. Spring stratification drives a bloom of growth of the microscopic phytoplankton that are the base of marine food chains. During summer the surface layer is denuded of nutrients and primary production continues in a layer inside the thermocline, where weak turbulent mixing supplies nutrients from the deeper water and mixes oxygen and organic material downward. Tidal flows generate turbulence; the strength of turbulence controls the timing of the spring bloom, mixing at the thermocline, and the timing of remixing of the water in autumn/winter. Determining the interplay between mixing and stratification is fundamental to understanding how shelf sea biological production is supported. Arrays of large, floating wind turbines are now being deployed over large areas of seasonally-stratifying seas. These structures will inject extra turbulence into the water, as tidal flows move through and past them. This extra turbulence will alter the balance between mixing and stratification: spring stratification and the bloom could occur later, biological growth inside the thermocline could be increased, and more oxygen could be supplied into the deep water. There could be significant benefits of this extra mixing, but we need to understand the whole suite of effects caused by this mixing to aid large-scale roll-out of deep-water renewable energy. eSWEETS will conduct observations at an existing floating wind farm in the NW North Sea to determine how the extra mixing generated by tides passing through the farm affect the physics, biology and chemistry of the water. We will measure the mixing of nutrients, organic material and oxygen within the farm, and track the down-stream impacts of the mixing as the water moves away from the wind farm and the phytoplankton respond to the new supply of nutrients. We will use autonomous gliders to observe the up-stream and down-stream contrasts in stratification and biology all the way through the stratified part of the year. We will use our observations to formulate the extra mixing in a computer model of the NW European shelf, so that we can then use the model to predict how planned renewable energy developments over the next decades might affect our shelf seas and how those effects might help counter some of the changes we expect in a warming climate. Stratification is so fundamental to how our seas support biological production that we will develop a new, cost-effective way of monitoring it. We will work with the renewables industry and modellers at the UK Met Office on a technique that allows temperature measurements to be made along the power cables that lie on the seabed between wind farms and the coast. Our vision is that large-scale roll-out of windfarms will lead to the ability to measure stratification across the entire shelf. This monitoring will help the industry (knowledge of operating conditions), government regulators (environment responses to climate change) and to operational scientists at the UK Met Office (constraining models for better predictions).

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 well-motivated, relic particles in 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 electroweak-scale particle dark matter in the accessible parameter space remaining above the very challenging neutrino background. Exciting opportunities exist also in neutrino physics, including establishing the existence of neutrinoless double-beta decay; this is another paradigm-shifting discovery which may be accessible to 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 manufacture underground, 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

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.