UNIVERSITY OF EDINBURGH

UKRI Gateway to Research · FY 2025 · 2025-02

Salmonella enterica is an economically important bacterial pathogen that compromises food safety and One Health globally. Cattle are a major reservoir of Salmonella including S.Dublin, which causes invasive disease in cattle. S.Dublin spreads via the bloodstream to internal organs causing severe and often fatal disease in calves and abortions in pregnant cows. Adult cattle can carry S.Dublin asymptomatically and shed S.Dublin in faeces and milk leading to its spread within herds and into the foodchain. Over 25% of herds in the UK are infected with S.Dublin and it is the predominant serovar isolated from cattle. S.Dublin is a zoonotic pathogen. The consumption of raw milk and raw milk products and direct contact with infected animals are major risk factors for human disease. S.Dublin causes invasive disease in humans. It is at least 30% more invasive than Salmonella serovars that cause gastroenteritis; over 75% of S.Dublin patients need hospitalisation compared to the 27% infected with other serovars and the fatality rate is 4-15% compared to 0.3% for other serovars. The bacterial factors responsible for this invasive behaviour in cattle and humans are poorly defined. S.Dublin is an emerging public health concern. It is difficult to eliminate from cattle herds. There are an increasing number of incidents related to human consumption of raw milk in the UK. Outbreaks due to raw milk and cheese have been reported in Europe. Multidrug resistance is being increasingly reported in cattle and human isolates globally, and there are currently no effective vaccines against S.Dublin. We will use cutting-edge genome sequence analyses combined with observations of virulence in multiple in vitro and in vivo models to define genetic markers of virulence and zoonosis. Guided by publicly available short-read sequence data for S.Dublin, we will assemble a collection of genetically diverse isolates from cattle and humans and use established assays to screen for virulence in bovine and human epithelial and immune cells. We will perform long-read sequencing to characterise additional variation in S.Dublin genomes like large-scale rearrangement of chromosomal fragments and to detect the presence and features of extrachromosomal DNA molecules like plasmids with antimicrobial resistance genes. We will identify isolates with high- and low-virulence profiles using correlation and genome-wide association analyses to define genetic markers of overall in vitro virulence and markers specific to increased virulence in human cells. We will confirm the role of defined markers in vivo using our established ethical 3Rs sequencing-based method in cattle, which are an excellent model for human salmonellosis, thereby maximising the benefits of our research to animal and human health. Our preliminary genomic analysis has already recognised core-genome diversity beyond the predominant genomic cluster, sequence type 10, and variable distribution of acquired virulence factors like the S.Typhi Vi capsular polysaccharide. We also identified large-scale chromosomal rearrangements in S.Dublin genomes using long-read sequencing and found that isolates that vary in sequence type or genome structure exhibit differential virulence in vitro in immune cells. This research will advance our fundamental knowledge of S.Dublin virulence by linking genotype to phenotype. Defining genetic markers to predict high-risk isolates will provide valuable information to animal and public health stakeholders that aligns with long-term BBSRC research priorities to improve surveillance and control programmes; prevent zoonoses; improve food safety; ensure safe and sustainable agriculture; and identify targets to develop effective vaccines and interventions and drive innovation.

UKRI Gateway to Research · FY 2025 · 2025-01

This collaboration will address issues of educational inequalities and marginalisation in São Bernardo, a municipality in the state of Maranhão, Brazil. Specifically, our goal is to improve the Youth and Adult Education (EJA) programme, an educational modality within the Brazilian system designed to offer opportunities to individuals who lacked access to, or were unable to complete, their studies during the conventional schooling age. Maranhão ranks second to last among Brazil's 26 states in educational performance (Maranhão, online). The principal challenges of this programme include: a) high dropout rates driven by economic pressures, b) quality of education hampered by a shortage of qualified teachers, and c) inadequate infrastructure, especially in rural regions (Reis; Sousa, 2015). These obstacles significantly impair the educational experiences of marginalized groups (e.g., indigenous communities). English language education becomes even more critical in circumstances such as these where students may lack the vision to see the benefits of learning a foreign language, ultimately affecting their motivation and engagement. The overarching objective of this project is to facilitate collaborations between the UK and Brazil academics and relevant stakeholders to enhance the quality of English language education for students enrolled in the EJA programme. Specifically, we propose the following aims: (i) to understand the expectations of local stakeholders regarding improvements to the EJA programme; (ii) to conduct a document analysis of local policies underpinning this educational programme; (iii) to design pedagogical activities inspired by the concept of life capital, a framework which fosters a focus on students' life stories; (iv) to pilot such activities through a small-scale pedagogical intervention (pilot study); and (v) to organize knowledge exchange events in Brazil and the UK to promote a multi-tiered dialogue based on this educational intervention with the aim of gathering feedback for a larger-scale study. To achieve the above aims, we will implement the concept of life capital, developed by the UK project leader (Consoli, 2021; 2022), as a pedagogical tool to promote a contextually-sensitive approach to language teaching, ultimately aiming to increase student motivation and engagement. Life capital is a theoretical construct which encourages educators to recognise and incorporate students' life stories in their teaching practice, thereby maximising learning opportunities and restoring a sense of self-confidence and value in their own education. This approach is especially pertinent in São Bernardo where students' lives are often disrupted by social inequalities. Therefore, this life capital driven pedagogy will empower individuals by inviting them to see their unique life experiences less as inhibiting but more as strengths to support and facilitate their education. The anticipated benefits and outcomes of this project include the revision of local policies supporting the EJA programme, with guidance from the state Secretary of Education, who will serve as a consultant throughout the project. Additionally, the direct involvement of local English language teachers will facilitate the integration of life capital as a pedagogical tool in their language classes. Consequently, students will shape their learning experiences around their unique life narratives, enabling them to recognise the positive aspects of their life trajectories (e.g., resilience) and ultimately (re)gain motivation in learning English in a manner that is both cognitively and emotionally fulfilling. The results of this pilot project will be shared with teachers, student-teachers, and teacher educators in Brazil and the UK through knowledge-exchange events organized at the two researchers' respective institutions.

UKRI Gateway to Research · FY 2025 · 2025-01

All the genetic information required to build a human is stored in 2m of DNA, in each cell of our body. The DNA is organised in thousands of functional units, the genes, many of which are constantly transcribed into RNA, to make proteins. The DNA also needs to be copied, or replicated, to grow a 37 trillion-cell human body from a single cell. How do DNA replication and transcription manage to coexist without interfering with each other? We hypothesise the existence of a mechanism separating the two processes in space and time to avoid the physical collision of the replication and transcription machineries. To test our hypothesis, the first step is to map exactly where the two machineries normally sit on the DNA, at any given time. Until recently, we did not have the necessary technical resolution to create a meaningful map and we had only very low-resolution imaging data that told us that the transcription and replication machineries are separated in space. The development in the last three years of new genome-wide approaches finally provides us with the tools to establish their exact location at high temporal and spatial resolution. We will therefore map the position of the replication forks and the transcription machinery and create an open resource to enable user-friendly access to our results. This will maximise the value of our research, extending it to the entire scientific community. Our preliminary data suggest that one specific pathway that controls DNA replication in time and space, the DNA replication-timing program, is implicated in maintaining transcription and replication separation. We will perturb this pathway and determine the effects on the reciprocal position of transcription and replication machineries at high resolution. Finally, it is already known that conflicts between transcription and replication destabilise the genome and can contribute to neurodegenerative diseases and cancer. We will establish if the cells where we have eliminated the DNA replication-timing program indeed undergo genome destabilisation due to transcription-replication conflicts. The significance of this project is therefore three-fold. Firstly, by leveraging the most recent technological developments, our results will enable for the first time a genome-wide integrated vision of transcription and replication. Secondly, we will reveal a key biological principle, discovering a molecular mechanism that preserves genome stability, potentially in all eukaryotes. Thirdly, our data will provide a new molecular understanding of the events that lead to genome instability, thus potentially paving the way to new therapeutic approaches in the future. Our proposal aligns therefore with objective 3.2 of the BBSRC strategic plan "Understanding the rules of life".

UKRI Gateway to Research · FY 2025 · 2025-01

The context: In the UK, ~1-in-1000 people are diagnosed with polycystic kidney and liver diseases (PKD and PLD) where fluid-filled cysts grow within these tissues. The development of cysts necessitates non-curative surgery or organ transplantation; however, most patients are ineligible for treatment and cystic disease substantially reduces their quality of life. The mechanisms by which liver tissues become cystic are poorly understood, yet treating liver cysts is a priority for many patients and has been identified as an area of substantial unmet need by the UK PKD charity(1). In PKD, where cysts form across the kidney and liver, the majority of patients have mutations in PKD1 which promotes cyst growth by affecting the formation of a receptor channel complex that locates to the primary cilium, a sensory and signalling organelle found on most cells(2,3). In isolated PLD, a rare disease where cysts only form in the liver, patient tissue demonstrates shorter, dysmorphic or absent cilia on cholangiocytes (cells that line the liver bile ducts) suggesting cilia de-regulation is a likely driver of PLD(4). The core team and project partners on this proposal have a history of collaborating to improve our understanding of PLD. Our recent work (Waddell et al. Science Translational Medicine, 2023) demonstrated that loss of cholangiocyte primary cilia per se promotes PLD by reactivating developmental signalling pathways(5). The challenge: There are currently no clinically available treatments for PLD. While clinical trials exploring the use of Somatostatin analogues (inhibitors of cAMP signalling) have been positive(6), not all patients respond to treatment and following treatment withdrawal cysts rapidly regrow. There remains a clear clinical need to understand the molecular mechanisms by which cysts form in PLD and using this knowledge define whether modulating these processes limits cyst growth. Our aims: In this project, we bring together world-leading clinical and non-clinical researchers, industrial partners and patients to build on our cutting-edge discoveries thereby accelerating clinical translation. Our fundamental objectives are to (i) determine how cystic cells in PLD recruit and pattern an inflammatory microenvironment and (ii) define if we can manipulate this inflammatory microenvironment to reduce cyst growth. Our project comprises three specific aims: Aim-1: How does cholangiocyte cilia dysfunction promote an immune-high state? We will engineer human organoids to carry PLD-specific mutations to mechanistically define how dysregulated cilia promote cystic cholangiocytes to recruit an inflammatory microenvironment. Aim-2: How is the microenvironment co-ordinated to drive PLD? Using human PLD patient tissue we will spatially map the cystic inflammatory microenvironment and using a mouse model of PLD understand how these microenvironments co-evolve as cysts form. Aim-3: Can local tissue immune cells be re-patterned to be anti-cystic? In partnership with Pliant Therapeutics, we will modulate local tissue inflammation to re-pattern cyst-associated immune cells and define whether these target cystic cholangiocytes to reduce cyst growth. The applications and benefits: PLD is currently incurable and substantially impacts a patient's quality of life. Only by understanding the pathobiology of PLD we will be able to develop effective clinical interventions for this disease. This project fundamentally addresses how primary cilia dysregulation in cystic cells drives local tissue inflammation in PLD. By bringing together a diverse group of researchers to dissect the PLD disease process at high-resolution, there is significant potential to develop therapeutic strategies to limit disease progression and improve the lived experience of patients with PLD.

UKRI Gateway to Research · FY 2025 · 2025-01

Digital Research Infrastructure (DRI) is now ubiquitous in research. It has revolutionised the way that we conduct research, pervading all aspects of the research lifecycle. From the use of large-scale computing for machine-learning and big data to modelling and simulation, to the management of experiments for record keeping and reproducibility, research is powered by the software and hardware that have become vital tools and resources for the modern researcher. This requires new skills and forms of research collaboration, as research supported by DRI aims at larger scales and interdisciplinary collaboration. This project targets UKRI’s DRI skills strategic priority, focussing on the need to grow the digital skills base to ensure more effective use of DRI from a diverse set of users. We already observe significant skills shortages in these areas, partly because the training materials and infrastructure are not sufficiently well developed and integrated, and partly because career pathways and opportunities are lacking and don’t incentivise a long-term career in these roles. There is already a substantial body of DRI-related training resources, primarily targeting foundation level skills for researchers (e.g. The Carpentries, CodeRefinery), as well as more advanced material on technical topics for research software engineers (RSEs) and experienced researchers (e.g. ARCHER2 training). To address the challenge of improving access to, and usability of, DRI from across all of UKRI, and broaden engagement to new users and communities, we need to address: Lack of DRI training for research support roles, such as research facilitators Lack of DRI training for interdisciplinary research teams / supporting team science Lack of visibility of DRI outside of physical sciences and engineering Developing support for the research facilitator role is particularly important as they play a vital and trusted role in helping to build and strengthen links between technical professionals and the research community, enhancing the impact of the type of skills development activities we are undertaking. This project involves partners who have worked together through the Software Sustainability Institute and the UNIVERSE-HPC training project to develop approaches, infrastructure and materials to support DRI training. Pioneering new approaches include the development of personalised learning pathways to help learners understand what training they require at the current stage of their career; the open-source Gutenberg teaching platform that simplifies course delivery in multiple formats; the development of new intermediate level courses on research software skills; and innovative learning formats such as “Byte-sized RSE” and Research Software Camps designed to engage a more diverse set of participants. Together, we will: Develop new courses with domain-specific examples (adapting existing materials) that provide research facilitators with the expertise and confidence they need to disseminate the benefits of using DRI thereby encouraging new users and communities to make use of DRI. Encourage more sustainable, effective use of DRI by research teams by developing new courses (based on existing and new materials) to cover team-based skills such as project management, working in interdisciplinary teams, and knowledge exchange. Develop new approaches to delivering technical material to engage both new and existing audiences and increase visibility and understanding of DRI - e.g. through the use of Raspberry Pi clusters to support hands-on HPC and computing infrastructure training - helping address the skills shortage in key technical areas   We confirm we have received an invitation to apply, originally sent to Neil Chue Hong.

UKRI Gateway to Research · FY 2025 · 2025-01

There is growing demand for climate resilient solutions to address food security and biodiversity loss threats. Indigenous knowledge offers climate adaptation and biodiversity conservation solutions. However, Indigenous agricultural and botanical data are often recorded and digitised without the permission of, or with limited input from, Indigenous Peoples. This results in the co-option or even theft of ancestral knowledge, and the exclusion of Indigenous Peoples from research and governance processes, including any benefits arising from the use of their knowledge. As the need for a diversity of options intensifies, it is vital that climate adaptation research and policy incorporates Indigenous perspectives, including Indigenous-driven mechanisms to protect and value their knowledge systems. Our project responds to the pressing need for fundamental research into agricultural, botanical, and climatic research and governance frameworks that align with Indigenous ways of knowing, doing, and being. Drawing from transdisciplinary thinking, we will develop ethical, Indigenous-centred solutions to protect biodiversity and restore the use of native plants to feed and heal Caribbean populations. We aim to: Strengthen intergenerational climate resilience in Jamaica and Trinidad and Tobago; Advance new approaches to seed data governance with and for Indigenous Caribbean Peoples; Develop hybrid (Indigenous/Western scientific) tools and ethical protocols for safeguarding ancestral knowledge; Support recent efforts to reclaim Indigenous Caribbean lifeways by counteracting their invisibilization among policymakers, scientists, and wider publics. We will achieve these aims through four objectives: Document Indigenous-managed seeds and wild plants, and seed 'commoning' practices, through ethnographic, Indigenous storytelling, and ethnobotanical research. Commoning refers to the dynamic community processes of co-producing and co-managing shared resources. Outputs for this work stream (WS1) will include a children's e-book, plant heritage trails, and preliminary Ethical Protocols for Biocultural and Bioclimatic Research with Indigenous Peoples, which we will continue to hone in WS2 and WS3 (Aims 1, 3). Establish pathways towards Indigenous Data Sovereignty, or the right of Indigenous Peoples to govern data about their communities, lands, and resources. Building on the findings and ethical protocols developed in WS1, we will carry out a series of co-design and Indigenous storytelling workshops (WS2) to develop a bottom-up approach for securing individual and collective rights to seed data access, benefits, and privacy. WS2 will enable us to develop an Indigenous Seed Data Sovereignty Roadmap to guide future data-driven research with participating communities (Aim 2). For WS3, we will test the ethical protocols developed in WS1 and WS2 in a participatory bioclimatic modelling workshop. Holistic, ethical approaches to safeguarding ancestral plant and knowledge require an understanding of possible current and future changes and stressors, coupled with a deep sensitivity to Indigenous worldviews and ways of life. This is vital for ensuring culturally appropriate, sustainable governance options that withstand the global climate crisis. Held in each country, the workshop will bring Indigenous elders together with local climate scientists to explore how Indigenous-managed plants and practices can foster future climate resilience in the region (Aim 3). Strengthen the status and visibility of Indigenous Caribbean Peoples and the importance and longevity of their agricultural and botanical knowledge. Drawing from WS1-3, we will co-develop a Hybrid Framework for Indigenous Food Security, which highlights the research findings and includes the finalised ethical protocols. The Roadmap and Framework will be used to develop knowledge exchange activities and outputs, including a policy brief and International Dissemination Workshop (Aims 3, 4).

UKRI Gateway to Research · FY 2025 · 2025-01

Aims and Objectives We aim to improve and empower three census-linked products for the 2022 Scottish census. The three products we will work on are: Improving the Equalities Protected Characteristics data Annual Survey of Hours and Earnings (ASHE) to census linkage (ASHE-census) A high-fidelity synthetic data set for ASHE-census These census-linked products will be some of the first be created and accessed by researchers under the new "ready and reuse" model in Scotland. During four interactive training events, we will promote the census-linked products and disseminate knowledge to researchers on the system transformation happening in Scotland. Potential applications and benefits We will achieve our aims by completing four work packages (WP). WP0: Promoting and maximising user engagement and census-linked data value. This work package will underpin all census-linked products. Our approach will enable researchers to understand the original sources of census-linked data, the processes required to provision census-linked data, and how researchers can access and work with census-linked data efficiently. WP1: Improving the Equalities Protected Characteristics Research Dataset (henceforth Equalities). Administrative Data Research Scotland (ADR-Scotland) will deliver a standard update to the Equalities 2022 dataset, which will include data for people living in Scotland in 2022 who were not in Scotland in 2011, and, for the first time, include records of sexual orientation and trans status. While ADR-Scotland process these standard updates, we will be using the proposed ESRC grant to commission critical public engagement work on the acceptability of protected characteristics data and future research use. After the update has been completed, and as part of this ESRC proposal, we will analyse and explore potential improvements to the Equalities 2022 linkage to capture longitudinal changes in protected characteristics, particularly disability status. The exploratory longitudinal analysis and public engagement work are not currently planned by ADR-Scotland. WP2: Empowering a cutting-edge census-linked product with the potential to improve our understanding of Scotland's workforce and start informing a future business spine. We will link the ASHE for Scotland with the 2022 census (hereafter ASHE-census). This data product will independently enable researchers to understand Scotland's workforce surrounding the COVID-19 pandemic. ASHE-census will then enable future linkages to other data, empowering researchers to better understand the health and social experiences of Scotland's workforce. The ASHE-census represents added value and a unique opportunity to test the probabilistic linkage methodology required to inform a future business spine for Scotland. WP3: Developing a synthetic data set. Creating a high-fidelity synthetic dataset for ASHE-census linkage will maximise use by raising awareness of census-linked data and support researchers to work with data prior to full application. Impact on enabling excellent social science led research All collaborators are leading the changes to Scotland's data linkage landscape, moving from "create and destroy" to "ready and reuse". We will use the proposed ESRC grant to accelerate these census-linked products into the Scottish National Safe Haven using a streamlined technical process and the recently launched Researcher Access Service. This represents time and resource efficiency savings for the provision of census data to researchers.

UKRI Gateway to Research · FY 2025 · 2025-01

The GAIA Data Mining Platform project team has requested IRIS to provide sufficient Ceph storage and overall system resilience on their deployment operating on the Somerville Cloud in Edinburgh. They need ~530TB of triple replicated storage on the existing Ceph cluster and a new hypervisor in order to meet the expected needs for the Gaia DR3 release.The Ceph storage will be used for serving the bulk of the Gaia DR3 database to users of the data mining platform, and the hypervisor will allow the system to remain online during routine maintenance of the backing cloud infrastructure. The Somerville Cloud team have spec'd out the necessary hardware which amounts to 3 new Ceph servers and a single hypervisor with ~36TB of local NVMe SSD storage. These server specs match those of existing systems on Somerville and can be procured through a recently competed purchase agreement. They will be deployed on the Somerville Cloud, and the Gaia DMP project will have the respective resource quotas increased to allow use of the new resource.

UKRI Gateway to Research · FY 2025 · 2025-01

Ghana, located in West Africa, has a population of approximately 33 million people, with a large proportion of the population dependent on agriculture for their livelihoods. Livestock production, including cattle, sheep, goats, and poultry, is a vital component of the country's agricultural sector, contributing to food security and rural income. As of recent estimates, Ghana is home to around 2.5 million cattle, with a significant portion of these animals raised by smallholder farmers, particularly in the northern regions, which play a key role in the national economy. However, the livestock sector faces significant challenges from various livestock diseases, which affect both productivity and the livelihoods of farmers. These diseases can lead to high mortality rates, reduced fertility, lower milk and meat production, and increased costs for treatment and prevention. Several factors contribute to the persistence and spread of livestock diseases in Ghana, including inadequate veterinary services, climate change, poor biosecurity practices, and limited access to education and training for farmers, with many of the diseases being brought in to the country from neighbouring countries whilst trading livestock. In recent years, new and emerging livestock diseases have become a growing concern in West Africa, with outbreaks such as African swine fever (ASF) and the re-emergence of foot-and-mouth disease (FMD) threatening animal health and food security. The rapid spread of these diseases, often exacerbated by factors like climate change, increased livestock movement, and inadequate biosecurity measures, underscores the need for robust surveillance systems. Effective surveillance is crucial for early detection, monitoring the spread of diseases, and implementing timely control measures to prevent large-scale outbreaks and mitigate their socio-economic impact on farmers and local communities. The objective of this travel award is to join a meeting proposed off the back of a training programme being run by colleagues in Ghana on epidemiological data analysis and specifically network analyses and long-read sequencing for trans-boundary animal diseases. These funds would allow two additional staff from the Roslin Institute to join the training programme to further share knowledge and expertise and to have broader discussion on animal health in Ghana with the ultimate aim to develop research proposals with our Ghanaian colleagues from the University of Ghana and the Accra Veterinary Laboratory who initiated the original approach for the training.

UKRI Gateway to Research · FY 2025 · 2025-01

Particulate solids (granular materials) encompass natural soil deposits, pharmaceutical powders, food ingredients (e.g., powdered milk, flour), aggregates and cement used in construction, etc. Particulate solids are often inputs to manufacturing processes or are produced as intermediate/final products. They have economic and societal importance. They are fundamental to the UK chemical & pharmaceutical industry which, in 2023, generated £60bn of exports, added £30.4bn to the UK economy and supported a workforce of over 130,000 people (Chemical Industries Association, UK Industry Snapshot). The UK Mineral Products Association estimates that the mineral products industry directly contributed over £7.9bn to the UK economy in 2021 (turnover of £21.6bn) and directly employed 80,000 people by producing 419 million tonnes of material, mostly in particulate form. Efficiency improvements in handling and processing these materials will bring economic benefits and reduce their associated carbon footprint. Particulate solids form complex systems with material behaviours that are difficult to understand and predict. For example, sand can lose strength during earthquakes causing building collapses, grain silo collapses continue to cause loss of life, and lunar soil behaviour determines equipment design for space exploration (NASA Technical Memorandum 2010-216257). Particulate solids simulations explicitly model particles and their interactions to provide insights into behaviour that are difficult, or impossible, to obtain experimentally. For example, we cannot embed sensors in high-temperature environments such as blast furnaces. The most popular particle-scale simulation method is the discrete element method (DEM). The world’s first DEM code was developed by Peter Cundall during his PhD at Imperial College London in the 1970s. Since the early 1990s there has been an exponential growth, internationally, in the use of DEM in scientific research. UK-based researchers lead the development and exploitation of open-source DEM codes and high-performance computing (HPC) to enable simulations of problems at scales with industrial relevance. Despite the UK’s leadership in particulate solids simulations, there is no overarching UK community including representatives from the different disciplines that exploit DEM and related methods. Developments happen in discipline silos, inhibiting full exploitation of methodological advancements. CCC-ParaSolS will unite scientists and engineers from academia and industry with a common interest in simulating particulate solids for a variety of applications. We will build on existing discipline-specific networks with a strong DEM interest, e.g., the UK micro–macro soil mechanics group. The community will embed diversity and inclusiveness in its composition, governance, and activities, considering gender, career stage, scientific discipline, etc. CCC-ParaSolS will promote the use of open-source software and best practices in validation, benchmarking, and research data management. Bespoke training on DEM (using established open-source codes), HPC (using ARCHER2), reproducible research, and FAIR data principles will be delivered by code developers, EPCC, and the Computational Science Centre for Research Communities (CoSeC). We will design the training programme to be inclusive of historically underrepresented groups. Through community consultation, CCC-ParaSolS will identify gaps and barriers in our current simulation capabilities and training that are inhibiting high-impact scientific discoveries and slowing the transition from workstations to HPC and from CPUs to GPUs to improve energy efficiency and performance. Based on this community needs analysis, one or more high-priority code development projects will be carried out, led by CoSeC. CCC-ParaSolS will create a five-year vision for the community and produce a viable plan for a Collaborative Computational Project in particulate solids simulations (CCP-ParaSolS).

UKRI Gateway to Research · FY 2025 · 2025-01

Grasping Data will change how we think about children and their personal data. We go beyond current emphases on privacy and protection by co-creating cutting-edge, child-centred tools and pedagogies with young children, helping them understand and directly benefit from their own data. We achieve this by advancing diverse research fields of early learning, cognitive psychology, child-centred design, data ethics, data visualization, and computer science to explore the potential of Data Physicalization for children in their early years (aged 3-8) to construct (with adults) physical representations of their personal data that they can touch, explore, talk about and learn with. Our focus on the youngest learners pushes the boundaries of helping all ages to understand and benefit from data in an increasingly digital world. This proposal is time sensitive. Artificial Intelligence is accelerating ways children's personal data is already captured and processed by others. Toothbrushes monitor their hygiene, smart toys capture their conversations, activity watches capture their movement, education platforms record their (mis)behaviour. Yet children's consent for this data is either acquired through adult caregivers (who themselves may not be confident about data), or not at all. Whilst there are efforts to improve children's understanding of data, research and educational initiatives tend to focus on older children and online protection. Yet, personal data is likely to be highly engaging for young children as it can reveal much about themselves: where they have been, what they said, how active or loud they are. By creating new forms of representation and activities, Grasping Data will enable us to tap children's interest to help them understand and value their personal data, before thinking about whether to give it to others. The aim of Grasping Data is to empower young children by enabling them to create, explore, understand, and directly benefit from their personal data. The project's objectives will create methods for measuring children's understanding of personal data then develop new approaches, physicalization designs, and activities to improve understanding. In doing so, the project will advance our knowledge of the benefits of physical interaction in learning as well as how best to work in partnership with children. These objectives are addressed by working with over 270 children and three organisational partners in three contexts: in schools, Edinburgh Zoo, and Glasgow Science Centre. Work progresses from children using everyday physical materials like Lego to represent simple data like age or preferences, to cutting-edge interactive physicalizations dynamically representing personal data such as activity, location, or loudness. This interdisciplinary project will contribute knowledge across disciplines and outputs that can scale impact beyond academia: from personal data physicalization toolkits for educators to 3D mementos and exhibits that enhance and extend visitor experiences. The project will change perceptions of children and their data, and accelerate research activity, teaching practices, policy and ethical approaches that recognise young children's potential to understand and benefit from how their data is captured. Grasping Data will advance technologies to extend how we represent data - from screens to physical spaces - and lead to more active roles for all users in design, starting with society's youngest. The greatest impact of this project will be for children, who will engage, enjoy, and understand their data-saturated world better, and have greater confidence that they should, and can, play a role in the design of their futures.

UKRI Gateway to Research · FY 2025 · 2025-01

My PhD research explored how a rural community in Sri Lanka's dry-zone became a "hotspot" for chronic kidney disease unknown etiology (CKDu) and how villagers navigate the impacts of the disease in their day-to-day life. Through the fellowship I aim to build on this research to contribute to policy debates on rainwater, further the development of new participatory ethnographic research methods, and establish myself as a scholar at the forefront of an emerging sub-field concerned with interrelationships between global health and the environment in anthropology and STS. The following specific objectives will contribute to these aims in a synergistic way. Objective 1: Engage with key stakeholders and contribute to policy debates in Sri Lanka. To engage with key stakeholders, I will: (1) conduct a community consultation workshop in Mahiyangane with key informants of my research giving them opportunity to comment, offer suggestions, and even criticize it; (2) organize a stakeholder meeting in Colombo with CKDu researchers and policymakers to share my findings and consult them on a policy brief I will write. To maximize the impact of my research findings in policy arenas I will: (1) prepare a policy brief that draws on my PhD findings to propose rainwater as a viable alternative drinking water source for CKDu-affected communities in the dry zone; (2) bring together my background in water chemistry and the citizen science to explore the possibility of establishing a mobile water testing laboratory covering a wider geographical area in the dry zone Sri Lanka. To do this, I will conduct five networking discussions with local NGOs (Sarvodaya, Kidney Protection Foundation and Lanka Rainwater Harvesting Forum) and local universities (Rajarata and Peradeniya), to explore the feasibility of such work; (3) I will convene a media briefing and publish an op-ed in a local newspaper to give publicity for the policy brief. Objective 2: Establish myself as a leading scholar in anthropology of global health This fellowship will enable me to take my research to a growing academic audience interested in global health, environment, South Asia, and philanthropy. To achieve this, I will disseminate my research through: (1) development of a monograph for Cambridge/Cornell University Press from my PhD thesis; (2) publication of one peer-reviewed journal article in a leading anthropological journal (e.g. Anthropological Theory or Journal of the Royal Anthropological Institute); (3) presentation of my research findings at the International Conference on Health, Environment and Anthropology (HEAt), jointly organized by University of Edinburgh and Durham University; (4) apply for a Wellcome Early Career Award. Objective 3: Contribute to the integration of citizen science methods in anthropology This fellowship will enable me to bring citizen scientific and ethnographic research methods together to make anthropological research more inclusive, participatory and impactful. This will be done mainly through three activities: (1) publication of a peer-reviewed journal article, 'Citizen science and the ontological turn in anthropology'; (2) participation in the citizen science summer school at the University of Zurich; (3) design a micro-methods workshop at the Edinburgh Research Training Centre on "Citizen science methods in ethnographic research". Objective 4: Develop my teaching skills The fellowship will support me to develop my teaching skills by designing and delivering 2 guest lectures in Anthropology of Global Health (PGT) and South Asia in the World (UG), within the School of Social and Political Science.

UKRI Gateway to Research · FY 2024 · 2024-12

The University of Edinburgh Core Equipment Grant 2024 will support 3 discrete items of equipment: An enhancement of the University of Edinburgh’s capacity for in-depth high- throughput proteome analysis of engineered biological systems. This will expedite discovery and scientific translation through establishing reliable, reproducible, rapid and informative protein and peptide analysis at high throughput both to characterise engineered biosystems with genetic interventions and to produce high-value biologicals. An instrument to produce high-throughput measurements of a wide range of biomolecular interactions. The reliable extraction of kinetic parameters and measurement and characterisation of biomolecular interactions are critically important in drug discovery and development, as well as many other fields at the intersection of biophysics, chemistry, biology and medicine. An upgrade to the School of Informatics compute cluster to support state-of-the-art research in computer systems. Research in computer systems requires a flexible, configurable cluster of CPU nodes connected though fast networking. The School of Informatics runs such a cluster, which is however now at full capacity. Upgrading the network switch and host adapters and replacing an aging node will enhance the productivity of the cluster and make it possible to support additional research groups, enabling research which increase the diversity both of access and of the range of topics.

UKRI Gateway to Research · FY 2024 · 2024-12

This project assembles an international UK-Japan team that will bring together world-leading technologies to develop in vitro models of human kidneys, far better than those currently possible, for disease modelling and regenerative medicine. Conventional organoid techniques, which attempt to convert all pluripotent cells into kidney, produce poor organization compared to real organs, and significant contamination by inappropriate cell types. In mice, direct isolation of kidney rudiments from intermediate mesoderm of embryos is much better, with organotypic organization and no inappropriate cells, but this route is obviously not possible from human embryos for reasons of ethics and practicality. The Kyoto partners have engineered advanced reductionist models of pluripotent cell-derived human embryos – ‘axioloids’ – that develop axes, somites and neural tubes. They do not develop intermediate mesoderm, but are close. The Edinburgh partners have engineered synthetic biological embryonic organizers capable of driving local differentiation of embryoid bodies, including under optogenetic control. This project will synergize these two technologies, in different, parallel ways, to generate new-generation axioloids that include intermediate mesoderm from which kidney rudiments can be isolated. These will be fully characterized, at anatomical, physiological and single-cell RNAseq levels, and compared to existing databases of current organoids and of natural human kidney development. They will also be used in a demonstration of disease and treatment modelling, specifically of autosomal dominant polycystic kidney disease, a relatively common and serious congenital condition. The overall approach we are taking – of going from pluripotent cells to an advanced human embryo model, then isolating organ-specific rudiments from this – will be of use far beyond the kidney system on which we are focusing as a proof-of-concept. This is a radical alternative to current approaches, and promises much more realistic and useful model organs. The immediate beneficiaries of our project will be those working in disease modelling, treatment development and regenerative medicine in the kidney. Later beneficiaries will be those working with other organs and tissues, and long-term, greatest beneficiaries will be the patients who are helped by a much improved ability to produce realistic models of human kidney, and progenitors for renal regeneration. Our project design includes a strong focus on risk control, with development and evaluation of parallel approaches to induction of intermediate mesoderm, and a range of ‘fall-back’ alternatives if specific first-choice aims should prove unachievable. The overall management, responsibilities and credit are shared equally between the UK and Japan groups, with each taking a lead on specific parts but co-working being embedded in all. The proposal includes intense collaboration between the UK and Japan groups, including long staff exchanges for bidirectional training and deep immersion in the research culture of the host country, including visits to other institutes. We also have a detailed plan of international conferences, ‘sandpit’ competitions and visiting opportunities to include a widening circle of participants in UK-Japan collaboration, and to lay the foundations for a range of future projects in the field of engineering biology for advanced tissue models and for regenerative medicine, beyond this proposal and beyond its immediate participants. Our proposal is ethically uncontentious but, mindful of how this work could initiate a fast-growing new field, we have included continual ethical input by a specialist co-lead, to ensure that all involved are kept up-do-date with the evolving ethical landscape of advanced embryo models.

UKRI Gateway to Research · FY 2024 · 2024-12

The Fourier transform is a fundamental tool across mathematics, the physical sciences and engineering. Despite its enormous importance over the past 200 years, basic questions remain about the behaviour of the Fourier transform when applied to different classes of functions, and when the integral (or sum) used to define the Fourier transform will converge. Harmonic analysis is a branch of mathematics which grapples with these problems. Harmonic analysis is undergoing nothing short of a revolution, fuelled in part by the discovery that many core questions have nascent algebraic structure. This has led to the development of novel algebraic methods which have transformed the field and have brought about resolutions of many longstanding conjectures. Nevertheless, many of the most important problems in harmonic analysis are far from fully understood. The broad goal of this proposal is to harness the power of newly available tools to make progress on central problems in harmonic analysis and to develop new connections between these methods and other areas of mathematics. There are two intertwined themes: 1. Contrasting perspectives on the Kakeya Conjecture. The Kakeya Conjecture is a geometric problem concerning shapes which contain many (straight) line segments. The geometry of these shapes underpins many questions in harmonic analysis (as well as other areas of mathematics such as PDE, GMT and number theory) but is very poorly understood. This poses a major theoretical bottleneck. The project investigates two complementary approaches to the Kakeya Conjecture: the polynomial partitioning and sum-difference approach. The former relies on real algebraic geometry, whilst the latter relies on elementary arithmetic counting arguments. Both have produced deep partial results on the Kakeya Conjecture of comparable strength, despite addressing very different aspects of the problem. The main objective is to pioneer a hybrid method, which incorporates ideas from both approaches. 2. Multilinear Fourier restriction with curvature. The Fourier Restriction Conjecture is an important question about the behaviour of the Fourier transform. It acts as a bridge from the purely geometric Kakeya Conjecture to an array of problems in harmonic analysis and PDE with oscillatory features. The project will investigate the multilinear theory of Fourier restriction, seeking to exploit underlying geometric features of the problem such as curvature and convexity. Previous works have only exploited curvature in extremely limited settings. The main objective is to obtain a robust multilinear Fourier restriction theory with curvature. The project objectives constitute major milestones in harmonic analysis and have wide ramifications for theoretical research in the area. Since the Kakeya and Restriction Conjectures are intimately connected to a whole web of problems, spanning a broad range of mathematical disciplines, the project has the potential for tremendous impact in theoretic mathematics, with direct and indirect benefits to researchers in harmonic analysis, GMT, PDE and beyond. By targeting the fundamental Kakeya Conjecture along with the intertwined theme of multilinear restriction, which provides a gateway to applications, the team will maximise project outcomes. Key words: Kakeya Conjecture, Restriction Conjecture, Harmonic analysis, Fourier transform, polynomial partitioning.

UKRI Gateway to Research · FY 2024 · 2024-12

Understanding how the structure and physical properties of materials change under extremes of pressure and temperature is essential if we are to develop predictive capabilities on how materials work under such conditions, thereby driving innovation in material design and engineering for the improved materials of tomorrow. Much progress has been made in the last 20 years, to the extent that our understanding of how the crystallographic and electronic structure of matter changes when it is compressed to very high pressures has transformed completely in that time. However, the lack of suitable technologies has severely limited our ability to tackle two key "known unknowns": how do pressure-induced structural changes occur in elements, and how are the microstructure and physical properties of more complex materials, such as key binary alloys, affected by extreme pressures and temperatures. We will exploit our team's expertise in experimental high-pressure physics, combined with recent advances in high repetition rate lasers, and the unprecedented brightness and spatial coherence of next generation synchrotron and x-ray free electron laser facilities, to make definitive studies of phase transitions, transition mechanisms, microstructure, and material strength in key elemental and alloy systems using x-ray diffraction and imaging. In collaboration with our Project Partners, we will then use electronic structure calculations to understand the physics behind the observed material response, and thereby develop new understanding and improved predictive capabilities in the behaviour of matter at extreme conditions.

UKRI Gateway to Research · FY 2024 · 2024-12

Toxoplasma is an important foodborne parasite in terms of animal productivity, human health, and food safety. Toxoplasma is a major cause of abortions and still-births in livestock, particularly pigs and sheep. Chronic infection also increases the susceptibility of livestock to other devastating pathogens, such as porcine reproductive and respiratory syndrome virus (PRRSV) that can kill over 80% of infected pigs. In humans, Toxoplasma is the principal cause of coma and early death in HIV/AIDS patients, ocular disease and blindness in immune-competent individuals, and neurological disorders in the developing foetus. In terms of food safety, meat products from chronically infected livestock, particularly pigs, is the main source of foodborne human Toxoplasma infections. Except for a live attenuated vaccine for sheep, no safe anti-parasitic treatment or prophylactic approaches exists to target Toxoplasma in livestock and humans, making the development of novel tools to repel Toxoplasma an important priority for biomedical research. Interferon gamma (IFNg), an inflammatory immune factor, is critical to successful anti-parasitic responses to Toxoplasma in almost all hosts. For example, human macrophages or mice with defects in detecting IFNg are highly susceptible to Toxoplasma. Meanwhile, Toxoplasma secretes proteins into host cells that enable it to evade IFNg-induced cellular processes to establish a safe niche to replicate. Thus, the outcome of Toxoplasma infection, which varies significantly between host species, is a complex interplay between IFNg-induced host responses and parasite virulence mechanisms. Among livestock species, cattle are more resistant to Toxoplasma than pigs. For instance, acute infection is often asymptomatic in cattle but can cause fever, general weakness, and abortion in pigs. In preliminary studies, we confirmed that cattle and pig macrophages, which are also the cells preferentially infected in vivo, recapitulate this difference in susceptibility to Toxoplasma. First, we observed that IFNg-stimulated cattle macrophages are more resistant to Toxoplasma than pig macrophages. This difference was not observed in naïve macrophages, confirming an essential role for IFNg. Secondly, we observed differential expression of over 500 interferon stimulated genes (ISGs) between Toxoplasma-infected cattle and pig macrophages. Guided by these preliminary data, we postulate that difference in susceptibility to Toxoplasma between cattle and pigs is due to differences in Toxoplasma virulence or IFNg-induced anti-parasitic mechanisms between cattle and pigs. Here, we will address this hypothesis by using a panel of molecular biology and parasitology approaches, including CRISPR/cas9 gene knockout screens and parasite growth assays, to identify how Toxoplasma genes and ISGs control Toxoplasma infection in cattle and pig macrophages. The outputs from this work will advance our knowledge on the mechanisms that control Toxoplasma in cattle and pigs. In the long-term, information about ISGs that inhibit Toxoplasma in cattle or parasite genes that enhance parasite virulence in pigs, can be exploited to accelerate the development of tools to reduce the disease burden and zoonotic threat of Toxoplasma in pigs. In addition, the ISGs and Toxoplasma gene knockout system that we will developed in this proposal, will be useful tools to study other pathogens controlled by IFNg in cattle, including Neospora or Toxoplasma virulence mechanisms in other susceptible hosts, including sheep.

UKRI Gateway to Research · FY 2024 · 2024-12

This research examines the history of geographic knowledge and technology during the Latin American Cold War in Guatemala. After World War II, the US government recognised the need for uniform grids to guide long-range missiles and for detailed knowledge of local conditions. Beginning in 1946, the United States Army Map Service created the Inter-American Geodetic Survey to support Latin American national mapping efforts. By 1952, the IAGS was operating a free geographical surveying, cartographical drawing, and map reproduction school at Fort Clayton in the Panama Canal Zone. The school trained thousands of military and civilian personnel from across Latin America until it closed in 1992. IAGS-associated geographic knowledge and technology was never more important than within Guatemala's bloody civil war (1960-1996). Eager to take advantage of US support for more accurate maps, Guatemala signed a treaty with the US for IAGS-related mapping within two months of the programme's launch in 1946. By 1962, Guatemala's National Geography Institute (IGN) enabled the large-scale development programs designed to eliminate the social bases of the revolution including the building of roads, hydro-electric dams, and mines. In the 1970s, however, as guerrilla forces operating in the countryside gained momentum, the military sought more effective control over geographic knowledges to pursue its counterinsurgency aims. In 1972, the US military general responsible for Central America noted that the Inter-American Geodetic Survey (IAGS) provided essential information for assessment of guerrilla activity, which was taking place where "geographic knowledge was the weakest." These efforts to build strategic geographical knowledge reached a crescendo in the early 1980s, when the Guatemalan military sought to control the countryside through exclusive control over maps, the construction of model villages, the patrol of movement, and ultimately a massive scorched-earth campaign that raised over 600 villages. As an integral part of the state's counter-insurgency campaign, the IGN was transferred to the Ministry of Defense in 1982, where it remained until state institutions were demilitarised in 1998. The Commission for Historical Truth and Memory illustrated that the worst episodes of state-sponsored violence occurred in areas with mining operations and hydro-electric dams. Guatemalan guerrillas, as well as people displaced by war, also generated geographical knowledge when they sought to navigate familiar and unfamiliar territories and to build political futures beyond the view of the state. Guerrillas and displaced peoples navigated space through Indigenous and local knowledges of landscapes that were laden with social meanings, historical memories, and embodied other-than-human beings, such as mountain spirits. In the aftermath of war, Guatemalan artists continue to reflect upon the geographies of the war through art that merges critique with memory struggles over the tragic pasts. This research project seeks to reveal how geographic knowledges shaped the contours of insurgency, counter-insurgency, and development in one of the most pivotal countries in the Latin American Cold War. Drawing on novel visual methodologies and collaborations with Guatemalan artists, this research will reveal how geographic knowledges and technologies -- scientific, insurgent, and Indigenous --shaped a crucial and neglected theatre of the Cold War. Through a major international network, this research will also seek to create a new subfield of Cold War cartography. This project will result in an art exhibit, a historical GIS map, a scholarly monograph, co-authored articles, and an edited volume.

UKRI Gateway to Research · FY 2024 · 2024-12

My project addresses three open questions in nuclear astrophysics: the cosmological lithium problem, the origin of carbon, nitrogen, and oxygen (CNO) in first-generation stars, and the so-called electron screening puzzle. All have eluded possible explanations for over three decades. Despite appearing to be unrelated, these questions may all be reconciled by the quantum effect of nuclear clustering. This is a well-known phenomenon in nuclear physics, but its influence on low-energy nuclear reactions of astrophysical interest has remained largely unexplored until recently. The core idea of this project revolves around tantalising new evidence that nuclear clusters may enhance the fusion probability between certain light nuclei at very low energies and help answer the aforementioned questions. Specifically, new fusion processes involving highly clustered light nuclei have recently been suggested to efficiently convert primordial hydrogen and helium into the CNO nuclei needed to gravitationally support first-generation stars, formed a few hundred million years after the Big Bang. Intriguingly, these same reactions could also substantially alter the abundance of lithium in these stars, thus potentially solving the cosmological lithium problem, i.e. a factor-of-three discrepancy between the predicted abundance of primordial lithium and that observed in the oldest stars today. If low-energy nuclear reactions are indeed enhanced by clustering effects, the exceedingly high electron screening potential measured in laboratory studies of some astrophysical reactions could also be finally explained, with potentially enormous impact on fusion-driven energy generation. By adopting a high-risk/high gain approach of experimental, theoretical, and computational effort, my team and I will break new ground in elucidating the role and strength of nuclear clustering in astrophysical reactions, with far-reaching consequences in nuclear physics, cosmology, and astrophysics.

UKRI Gateway to Research · FY 2024 · 2024-11

Proteins and the nucleic acids DNA and RNA are the most fundamental building blocks of life. Proteins are chains of amino acids made from 20 different building blocks, the canonical amino acids. The genetic code is the cipher that connects proteins to nucleic acids. When proteins are produced, the sequence of nucleic acids is translated into a sequence of amino acids. There are 4 nucleotide bases of DNA and RNA organized in triplets. There are 64 triplets of which 61 are each assigned to one amino acid, while three triplets act as 'stop codons' and signal the end of the protein. The genetic code is the link between triplet codons and amino acids. The 'decoding' of the nucleotide sequence happens using transfer RNA (tRNA). A tRNA molecule contains a triplet codon on one end and the corresponding amino acid at the other end. The amino acid is attached to tRNA by an enzyme called aminoacyl-tRNA-synthetase (aaRS). The tRNA triplet binds to an mRNA triplet and an amino acid is added to the growing protein chain. Genetic code expansion is a technology whereby new tRNAs and aaRS are added to the cell, allowing it to make proteins using more than the 20 canonical amino acids. The additional amino acids, called non-canonical amino acids (ncAA), are chemically synthesized 'designer' amino acids with properties not found in nature. To specify where the ncAA should go within the amino acid sequence of a protein it is necessary to assign them to a nucleic acid triplet. Since 61 triplets are already assigned, this is normally done by making use of one of the three stop codons. We have previously established this technology in animals and we have used it to develop powerful in vivo tools that employ proteins modified by the introduction of ncAA. In this proposal we aim to take the next big step and develop a method allowing the use of multiple ncAA together, the first time this will be made possible in an animal. For this we will develop i) additional aaRS/tRNA pairs for use in C. elegans, which can be used together with existing pairs without cross-reacting, and ii) we will establish new 'blank' nucleotide codons to determine where in the protein the ncAA will be incorporated. We will explore the use of triplet stop codons other than the widely used UAG (amber) stop, as well as nucleotide quadruplet codons. We have recently shown that the use of quadruplet codons is possible in animals and can approach incorporation efficiencies close to that observed with traditional triplet codons. We will then use the technology to upgrade a method we have previously developed for controlling gene expression with light. Using the new ability to employ two ncAA we will be able to switch on or off two genes independently of each other. This is an important breakthrough and will allow us and other researchers to, for example, control the activity of single nerve cells in C. elegans and tease apart the functioning of the C. elegans nervous system with a level of precision that is impossible using existing methods. The technology we develop will also be immensely useful for researchers outside of C. elegans to study the basics of how life works in anything from bacteria to human cells.

UKRI Gateway to Research · FY 2024 · 2024-11

Electronically conductive metal oxides represent an extremely important class of materials which underpin technologies from smartphones to efficient catalysts. Surprisingly, they are also rare. Discovering better conductive ceramics could accelerate breakthrough technologies such as spintronic devices for more efficient data storage. Despite their increasing importance, however, there is currently no systematic way to develop new metallic ceramics. The first aim of this project is therefore to create a family of new conductive materials by substituting oxygen for fluorine; namely metal oxyfluorides. Oxyfluorides offer the ability to directly tune the electronic properties of materials whilst preserving the same atomic structure. Specifically, this project will focus on substoichiometric “Magneli” phases where the atomic structure results in high electronic conductivity. These materials also undergo metal-to-insulator transitions as temperature is varied; such behaviour could be used in thermally activated devices (e.g. smart windows) but are also of fundamental scientific interest due to how they arise. Magneli-type oxides are a small but interesting class of materials, therefore Magneli oxyfluorides present an exciting family of materials waiting to be discovered. Metal oxyfluorides offer chemical flexibility which could be harnessed in many other areas of materials chemistry such as magnetic materials or thermoelectrics, but their uptake has been hampered by difficulties in fully characterising their atomic structure (which underpins the observed properties). Despite these challenges, however, oxygen and fluorine have a strong tendency to adopt well-defined (cis- or fac-type) ordering around metal ions, offering additional influence over physical properties through the presence of “correlated disorder”. The second aim of this project is therefore to accurately determine the oxygen and fluorine arrangement in these new materials using detailed X-ray total scattering techniques and to understand how this structure influences the measured electronic properties. This analysis will also help to understand how the crystallographic structure (particularly crystallographic shear planes) interacts with local bonding of oxide and fluoride anions to promote (or disrupt) anion ordering. This knowledge could then be applied to discover other mixed-anion materials. Extending this further, the final aim of the project is to actively control the anion arrangement itself during synthesis using the influence of the underlying atomic structure and precise synthetic control. Such ”crystallographic engineering” has not been attempted before, and if successful could allow a much wider range of anion-ordered materials to be synthesised. This is of fundamental interest, but could also offer a new way to control the physical properties of materials by directly tweaking structure at an atomic level. The impacts of this project will be threefold; firstly, a large number of new metallic ceramic materials will be discovered which could be applied in existing applications (e.g. battery electrodes, catalysts), or advance new technologies (spintronics). Secondly, the link between anion order and physical properties will be better understood, enabling the design of better materials. Finally, methods to directly control oxide-fluoride ordering would offer powerful control of atomic ordering, and could be applied in the future to the discovery of new materials unachievable using existing chemistry techniques.

UKRI Gateway to Research · FY 2024 · 2024-11

Biomedical science is changing rapidly, fuelled by technological advances such as Artificial Intelligence. The skills needed to take full advantage of these developments are also rapidly evolving, with research teams often now needing to include scientists who have crossed into biomedicine from other disciplines. These interdisciplinary researchers, however, often report not being welcomed saying, for example "If you are in-between disciplines, people on both sides consider you an outsider with little knowledge." A substantial minority of researchers experience hostility when working in interdisciplinary research environments. The vision for our "Hostile or Collegial research culture? Resources for data scientists" project is to: (1) Give voice to interdisciplinary scientists from all backgrounds who feel let down; (2) Draw from insights of researchers, industry, patient and public representatives to challenge longstanding issues in interdisciplinary research culture; (3) Develop evidence-based guidelines to improve this culture; (4) Test these draft guidelines in teams from partner institutions of Health Data Research UK and UK Dementia Research Institute; and (5) Integrate good research culture practices to maximise the future impact of UK biomedical data research. The interdisciplinary research culture guidelines will adhere to core principles of inclusivity, diversity, receptivity, respect, trust and a person-centred approach to science. They will cover authorship and contributorship to outputs, job description criteria, mentoring, privilege, and training. Research cultural change from these guidelines will be tested in 8 interdisciplinary project teams at two points, 1 year apart. Half of these teams will be randomly selected for 3 sets of interventions: (i) implementation of these guidelines, (ii) group and individual training to improve interdisciplinary research culture, and (iii) semi-structured interviews. Team members will be drawn from across diverse institutional settings, disciplines, career stages and professional roles, and will be partners in cross-institutional thematic teams. Four composite outcome measures will be compared between the two groups: Understanding the project's goals; Understanding team roles; Good communication channels; Clarity on authorship credit and intellectual property. Social learning will have occurred if interventions led to a change in individuals' understanding through interactions among team members. Our intent is to catalyse enduring change by integrating good practices into ongoing operations of research teams and organisations. The project will have lasting impact due to the skills and resources gained that sustain, advocate for, and extend improvements to interdisciplinary research culture. A final report will be produced with a media launch and prepared for journal publication. Our project team has experience in fostering inclusive and diverse research environments that value different perspectives, skillsets and experiences, and our institutions are committed to improve research culture. The project is designed to deliver and disseminate positive change using the experience of diverse stakeholders from 4 Universities, 3 Institutes (HDR UK, UK DRI and Turing), the public, patients, industry, early career researchers, data scientists, research software engineers and experimental biomedical scientists. By challenging the status quo, this project risks provoking antagonism. Disputes will be resolved using collaborations between researchers who hold different positions (i.e., adversarial collaboration). Personal data will be safeguarded in line with legal standards. The key Project Manager/Researcher role will understand the diverse perspectives of interdisciplinary researchers and will be well briefed in each participating institution's policies with respect to bullying, harassment and grievance, and relevant support mechanisms.

UKRI Gateway to Research · FY 2024 · 2024-11

BACKGROUND: Crohn's disease and ulcerative colitis are the common forms of inflammatory bowel disease (IBD) affecting up to 1 in 100 people in the Western world, with some of the highest prevalence rates in the UK (approx. 1.0%). Incidence rates are increasing sharply in the previously undeveloped world driven by a Western lifestyle. IBD typically manifests in adolescence / early adulthood with disturbed bowel function, a robust inflammatory response, systemic upset, psycho-social disturbance and substantial health-economic burden. Recent years have seen massive biotech / pharma investment in IBD with multiple different drug modalities now approved for use. However, remission rates are hitting a ceiling at 1 year of 30-40%, and no reliable biomarkers exist to aid with drug positioning. Management of IBD is further complicated by our inability to prognosticate on treatment response or disease progression. IBD develops in genetically susceptible individuals when there is a dysregulated mucosal immune response to a gut microbiota altered by Western diet and other environmental stimuli. A decade of gene discovery has yielded >250 susceptibility loci and multiple druggable targets. But it has not provided meaningful insights into disease phenotype or natural history. Having made substantial contributions to the UK and International IBD Genetics consortia, I have seen both the success of large sample sizes and the limitations of retrospective data capture in this highly complex and heterogenous disease. More recently, whilst working as a full-time NHS gastroenterologist, I have developed a programme of work to facilitate prospective biological and clinical data capture, both cost-effectively and at scale (recruiting 120-150 patients pcm). I now plan to expand this work to address a series of questions of fundamental importance to improving the outcomes of people with IBD. RESEARCH QUESTIONS: 1. What aspects of disease phenotype, diet, lifestyle, genetics and the gut microbiota contribute to a) disease flare, b) disease progression & c) treatment response in IBD? 2. How can we stratify patients based on disease biology and risk of progression? 3. Based on this, how can we intervene to improve outcomes? 4. Can we identify signals in samples taken before the development of IBD and intervene to prevent disease development in at risk individuals? RECENT WORK: I have established the PREdiCCt study and the Lothian IBD Registry. PREdiCCt has recruited 2629 patients with Crohn's disease and UC in clinical remission, and performed a deep dive into clinical, dietary, lifestyle, microbial and genetic factors at baseline. Patients have been followed up for a minimum of 24 months, with 60% followed for >48 months. PLANNED WORK: The PREdiCCt cohort will be analysed in detail to ascertain what aspects of habitual diet, the environment, microbiome and genetics are associated with and predict disease flare. We will performed an analysis of diet and microbiome interactions in a group of approximately 800 participants who have 4 day weighed food diaries completed. Psychosocial and quality of life parameters - collected longitudinally via monthly questionnaires will be analysed, including resilience. The Lothian IBD registry has been enriched with calprotectin data - a robust measure of gut inflammation in faecal samples - collected, and analysed using the same assay, over a 15 year period. Mathematical modelling will assign patients to different classes dependent on their calprotectin trajectories. These data will inform a dynamic clinical decision support tool to enable patients and clinicians to predict outcomes. OUTREACH: My goal is to improve the outcomes for people living with IBD. I want to build community globally and provide people with the tools for hope. I am doing this through multiple distributed media networks to provide a dynamic two-way knowledge interchange with all key stakeholders.

UKRI Gateway to Research · FY 2024 · 2024-11

Dramatic breakthroughs in our ability to actively manipulate the quantum mechanical properties of matter have led to landmark new technologies including trapped ion and neutral atom quantum processors. However, many of these new quantum technologies are extremely vulnerable to environmental noise and decoherence, restricting their technical capabilities and scalability. For future generations of quantum devices, we will need to develop better ways to preserve and protect the quantum mechanical phenomena that we wish to make use of. This is particularly important for quantum computers and quantum memories, where it is crucial that information is preserved over long timescales. The aim of the proposed research is to investigate to what extent impurities and disorder can be used to 'freeze' realistic quantum systems - namely open quantum systems subject to realistic sources of environmental noise - in the kind of exotic far-from-equilibrium configurations required for quantum computation. This work will enable the manipulation and preservation of robust, long-lived quantum states which can act as stable quantum memories, lessening the burden on complex error correction techniques by preventing the errors from happening in the first place. There are several high-profile examples of complex systems which are prevented from thermalising by the addition of some form of disorder. Two of the main examples are many-body localised matter, and spin glasses. Many-body localisation is a quantum mechanical phenomenon that occurs in low-dimensional quantum systems; it is a purely quantum effect, but is itself rather fragile. Spin glasses occur in highly frustrated, high-dimensional systems; they are robust, but the underlying principles are classical. The main aim of this proposal is to combine aspects of both to develop stable, long-lived non-ergodic phases of matter in two-dimensional open quantum systems, subject to realistic sources of environmental noise, comparable to the capabilities of state-of-the-art (noisy) quantum simulators. To achieve this goal, it will be necessary to develop numerical techniques capable of handling this challenging parameter regime. This key method will be the Tensor Flow Equation method which I invented and recently used to study the long-time dynamics of large two-dimensional quantum systems (arXiv:2308.13005). Using cutting-edge supercomputing resources and a radical redesign of the algorithm to make use of distributed parallelism, I will embark on an ambitious program to simulate some of the most challenging quantum phases of matter. This will be further augmented by a powerful set of AI-based tools to dramatically enhance the computational efficiency and scalability of the method.

UKRI Gateway to Research · FY 2024 · 2024-11

Understanding why galaxies - including our own galaxy, the Milky Way - look the way they do is a vital part of our mission to understand the Universe around us. At the centre of most, if not all, galaxies (including the Milky Way) lies a supermassive black hole, with a mass that is millions to billions of times the mass of the Sun. These black holes appear to be crucial component of galaxies, determining much of their structure and evolution, although how and why is still unclear. As a Future Leaders Fellow, my team and I are determining how these black holes grow, when this growth occurs within the lifecycle of a galaxy, and how these black holes affect the galaxies they lie in. Galaxies have long lives. They evolve slowly as the gas within them forms stars, these stars age over billions of years, and the overall shape and structure of a galaxy gradually changes. By comparison, the massive black holes at their centres appear to grow relatively rapidly, in short-lived "growth spurts" lasting at most a few million years. During these growth spurts, material falls towards the black hole, heats up and can produce huge amounts of radiation spanning the entire electromagnetic spectrum. A galaxy with such a growing black hole is described as having an "active galactic nucleus" or AGN. Over recent years, astronomers have started to understand the structure of the material close to a black hole that forms an AGN and how these structures produce radiation at different wavelengths - including X-rays, optical and infrared light and radio emission. These structures result in a wide range of observed phenomena in different galaxies, all of which can be associated with an AGN powered by a growing supermassive black hole. However, we do not know how these structures change over millions of years or longer for an individual AGN, over timescales relevant for galaxy evolution. My team and I are developing new techniques to connect the lifecycles of galaxies and their central black holes, probing timescales of millions to billions of years. Our studies reveal how material is brought into the centre of a galaxy, how this material forms an AGN, how the AGN changes and eventually fades over the course of many millions of years, what impact the AGN has on the galaxy during this time, and how often this whole process repeats throughout the lifetime of a galaxy. Studying processes on such long timescales is extremely challenging. We cannot watch a single galaxy over this time, so instead, we are using new surveys of the sky that provide "snapshots" of many millions of galaxies and their AGN, each at a different life stage. We have developed new methods to extract information from these static snapshots and are building new models to describe the lifecycles of individual AGN and explain what we see in these snapshots. We are also studying the properties of galaxies with (and without) AGN to determine whether certain types of galaxies are more likely to have an AGN. In doing so, we can determine which physical mechanisms within galaxies are responsible for driving material into their central regions and fuelling the periods of AGN activity. Our work combines data from an array of new astronomical surveys. We are using new surveys that are underway with the premier ground-based telescopes, measuring the spectrum of light from large samples of galaxies that is imprinted with vital information on their lifecycles, combined with new X-ray imaging of the sky provided by the recently launched eROSITA telescope as well as existing infrared data and new surveys at radio wavelengths that can be combined to track the variation in AGN structure within these galaxies.