University of Sheffield

UKRI Gateway to Research · FY 2024 · 2024-11

Factory+ is an established open and modular framework designed to standardise data management across domains. With a unified approach to data extraction, transport, storage, processing, consumption, and protection, Factory+ aims to become the standard infrastructure for modern industrial and research environments. The AMRC Connectivity Stack (ACS) is a practical implementation of the Factory+ framework, offering a comprehensive suite of open-source services that facilitate seamless integration of data systems within and across different sectors. This project seeks to significantly enhance Factory+ and ACS to support the evolving needs of the UK's digital research infrastructure. ACS has been in operational use for over four years, playing a pivotal role in collecting billions of data points at the AMRC and other research centres across the UK. It also serves large industrial partners, demonstrating its robustness and capability in real-world applications. Through the AMRC's partners, Factory+ is beginning to impact the strategies of world-leading commercial software vendors, further extending its influence across the industry. Our ambition is for Factory+ to continue expanding its reach and impact, establishing itself as the go-to framework for digital integration in manufacturing. This project is focused on enhancing Factory+ and ACS to address key challenges in today's digital landscape, such as ensuring continued alignment with modern authentication principles and implementing flexible, but structured, handling of both telemetry and static files across multiple domains. By implementing these changes we aim to transform how data is shared and used across different research and industrial domains, which aligns with UKRI's goals for a connected and innovative digital infrastructure. Ultimately, we aim to strengthen the UK's position as a leader in digital research infrastructure, driving collaboration and productivity across disciplines. The University of Sheffield Advanced Manufacturing Research Centre (AMRC) received an invitation to apply for this competition, with the original invite sent to Jonathan Eyre. As per the competition guidance, Eyre will be Project Lead on the Skills strand, and Alex Godbehere will be the Project Lead from the University of Sheffield AMRC for the Software strand (this application). PI eligibility has been approved with the DRI Team via email.

UKRI Gateway to Research · FY 2024 · 2024-11

Nitrogen (N) biotransformation processes underpin nutrient cycling and facilitate the biodegradation of many organic contaminants in water bodies. Chlorinated solvents (CS) and per- and polyfluoroalkyl substances (PFAS) are, respectively, one of the most widespread legacy and globally important emerging contaminants in aquatic systems. These organic chemicals may reduce the diversity of nitrifying and denitrifying microorganisms in the natural environment, but their effect as co-contaminants on the activity of N microbiota and N metabolism in the N-cycle is unknown. Previously, the biotransformation of N, CS and PFAS in aquatic media was examined in separate environmental compartments or in simplified lab environments, limiting their relevance and transferability of results. This makes protection of the N-cycle and remediation challenging in the context of climate change, which is expected to modify N fluxes to water bodies. NITROGENES aims to explore N-biotransformation in the presence of CS and PFAS co-contamination in multiple linked environmental compartments (river, hyporheic zone, aquifer) under changing climate temperature and hydrological stressors induced by climate warming. The project will combine field, lab and modelling studies and apply advanced isotope and microbiological methods. Field studies will be performed to deduce the impact of sediment geochemistry and catchment hydrology on N, CS and PFAS fluxes. Lab experiments will assess the role of PFAS molecular structure on N microbiota and the interaction with PFAS in mixtures with CS. Numerical models will be used to integrate the results of field and lab studies to determine longer-term changes in N biotransformation that may occur after exposure to PFAS and CS under different climate warming scenarios. NITROGENES will deliver modelling tools and guidance to manage and design strategies that protect N resources and mitigate impacts on freshwater aquatic ecosystems potentially affected by CS and PFAS.

UKRI Gateway to Research · FY 2024 · 2024-11

This award will enable training for the Sheffield Innovation Hub Head of Quality to become a Qualified Person (QP). This will enable completion of the appropriate QP training to fulfil the requirements of the QP study guide, to obtain the appropriate knowledge and experience to go for the QP viva, and to become QP eligible. Need: There is a strategic need to train QPs specialised in advanced therapies to increase size of the sector. There is a deficit in the number of QPs in the UK. The current requirement for QPs is high, meaning QPs can choose where they want to go based on various factors (salary, interest and working arrangements etc). Many QPs are at retirement age, meaning many of the currently registered QPs will likely be leaving the industry in the coming years or moving into positions as consultants.

UKRI Gateway to Research · FY 2024 · 2024-11

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 · 2024-10

Why isn't there more diversity of Life on Earth? There are millions of species on Earth, but many distantly related species have strikingly similar phenotypes, suggesting that biodiversity is in fact far less varied than we might expect. For example, sharks and dolphins have remarkably similar body shapes, but their most recent common ancestor lived over 290 million years ago. One reason for this repetition of forms is convergent evolution - the evolution of similarities in unrelated species. There are hundreds of examples of convergence in myriad traits including morphology, genes, ecological niches, life-history strategies and behaviour. Convergence is a central concept in evolutionary biology because it informs understanding of many fundamental evolutionary patterns and processes, including the role of constraints in evolution, morphological diversity, adaptive radiations and natural selection. Convergent evolution is often considered to be a ubiquitous feature of life on Earth. Yet, despite many striking examples and a long history of study, we currently lack a comprehensive understanding of both patterns of, and processes driving convergence. Many examples have never been properly quantified, and those that have been explored more thoroughly use a variety of methods, taxa, traits, and scales, preventing recognition of general patterns. We have identified two critical knowledge gaps and key questions: 1) A lack of understanding of broad-scale phylogenetic patterns of convergence. We will therefore ask, how frequently does convergent evolution occur at broad phylogenetic scales and how strong are examples of convergence? 2) A lack of understanding of the processes leading to convergence across evolutionary scales. To address this we will ask, what are the micro- and macroevolutionary mechanisms acting on species traits that lead to convergence? Advances in our understanding of the patterns and processes driving convergent evolution have been hampered by a lack of suitable methods and data. Answering the key questions above requires a new conceptual and analytical framework for understanding how convergent phenotypes evolve. To solve these challenges, we will develop a framework to measure the extent of convergent evolution and identify the most likely evolutionary routes to phenotypic convergence. Our methods build on microevolutionary and adaptive radiation theory, and recent methodological advances designed by the research team. We will develop and test the performance of our framework using our recently collected 3D beak morphology dataset from >8,700 bird species, which will allow us to test for convergence at multiple phylogenetic scales. We will then apply our framework to diverse examples of morphological evolution to identify broad-scale patterns in convergence across the vertebrate tree of life. The proposed research is timely because phenotypic datasets of such breadth and ecological relevance have only recently become available (and are rapidly increasing in number and trait/taxonomic coverage) and coincide with major advances in computational methods to assess convergence. The outcomes of our proposed work will provide a major advance in our understanding of convergent evolution. These advances are critical to driving a step change in our understanding of the nature of limits to evolution and, as a consequence, the processes that gave rise to the diversity of life on Earth.

UKRI Gateway to Research · FY 2024 · 2024-09

Northern Ireland's 'Troubles' were post-Napoleonic Europe's 'longest war': causing fully half as many deaths per capita as WWII did for the rest of the UK; and precipitating the longest continuous deployment in British military history. Moreover, though formally ended with the signing of the Good Friday/Belfast Agreement (GFA) in 1998, the Troubles continue to shape UK/Irish politics. Counter-terrorism powers initially framed as a temporary response to paramilitarism remain on Britain's statute book today. 'Peace walls' erected by the British Army to physically separate Catholic/Protestant communities still dominate Northern Ireland's urban landscape. And power-sharing institutions established under GFA find themselves trapped in cycles of repeat suspension - with party rivalries having left Northern Ireland government-less for 40% of the period since 1998. My fellowship advances important research to help us understand the Troubles' historical evolution, and persistent political legacies. My work situates Troubles-era security and peacebuilding policies in relation to a long-term 'genealogy' of Anglo-Irish relations, and provides a framework for tracing the historical roots of contemporary politics more generally. During my PhD, I created a new database of all UK parliamentary debates on Northern Ireland - from the latter's creation in 1920, to the outbreak of Troubles violence in the 1970s. I used quantitative methods of text analysis to establish patterns in ways British parliamentarians spoke about Northern Ireland, over these years. I found parliamentarians became habituated to knowing Northern Ireland according to a specific vocabulary - one framing Northern Ireland as an 'abnormal' 'problem' in need of 'solving'. I then set out to establish intersections between this historical scheme for knowing Northern Ireland on the one hand, and security policies advanced to contain its 1970s 'Troubles' on the other. I employed quantitative and qualitative methods of archival and spatial analysis to consider: 1) the introduction of the UK's first-ever 'counter-terrorism' laws in 1973/1974; and 2) the erection of peace walls between Catholic/nationalist and Protestant/unionist neighbourhoods in Belfast. I found that, in both conceiving and legitimising these interventions, British governmental and military actors relied on the same long-term vocabulary for knowing Northern Ireland I had established in my research's first phase. Troubles-era security policy grew out of historical patterns for thinking and speaking about Northern Ireland in British politics. My research on Northern Ireland affords important empirical, conceptual, and methodological insights. Empirically, it gives us tools to understand the origins of Troubles-era British security. Conceptually, it resolves problems in the treatment of history in scholarship on politics: illuminating how historical inheritances shape present political possibilities, and establishing a conceptual framework for assessing this shaping. Methodologically, my research offers an original and repeatable research design - combining quantitative and qualitative methods of analysis, to assess multiple 'modes' of data (textual, spatial, visual). My fellowship brings these contributions together through publication of a book on the histories of British security in Northern Ireland. It enables me to share my analysis with members of the public, policymakers, and disciplinary peers. Finally, it adds urgent research on Northern Irish peacebuilding to my existing findings on security: situating the Good Friday Agreement in relation to the same patterns of Anglo-Irish politics that produced 1970s security policies - and, in the process, demonstrating fault-lines at the heart of the GFA, which require addressing if Northern Ireland's devolved administration is to move beyond patterns of repeat suspension.

UKRI Gateway to Research · FY 2024 · 2024-09

Species distribution data is a key component of modern ecology. However, the unequal distribution of species records biases our understanding of ecological patterns, distorting impact assessments even for well-sampled regions. Therefore, quantifying the dimension of our ignorance in biodiversity information is essential to: 1) identify key knowledge gaps, 2) design research efforts that maximise scientific discoveries and 3) account for uncertainty in species distribution models. MarineGaps will attend to these demands adapting methods already employed in terrestrial systems to the global ocean. Specifically, MarineGaps will scrutinise marine big data in order to measure biodiversity ignorance at multiple layers (WP1), identify priority areas for data acquisition (WP2), and develop a software to account for uncertainty in macroecological models (WP3). Adopting an interdisciplinary approach, MarineGaps will generate results and provide tools to be exploited by both researchers and international organisations. All research outputs will be made freely available following FAIR principles. Through MarineGaps, the applicant will receive world-class training in big biodiversity data, learn a new programming language, and gain new skills on knowledge transfer and scientific communication. MarineGaps will be a benchmark for marine ecologists of the entire world, redefining the career of the applicant and providing him with an outstanding place to obtain a permanent research position in the European research space. The successful implementation of the project and achievement of the objectives is ensured by the solid tradition of the host institution with EU-funded programs, the expertise of the supervisors on the research topic, the experience of the applicant in handling large data sets, and a rigorous plan to achieve the project's goals in the effective time.

UKRI Gateway to Research · FY 2024 · 2024-09

What are social rights, and how do we articulate them? GLOSOC investigates how contemporaries since the late nineteenth century, and especially in the critical period between the end of the Second World War in 1945 and global economic downturn in 1973, have understood and expressed socio-economic rights: in particular, rights related to work (or choosing not to work), to earn one's own money and to maintain certain 'living standards'. This project suggests that work stands at the core of understandings of socio-economic rights and parses how the relationship between rights and work is contingent on different historical and cultural contexts. It focuses on these issues from a global perspective, charting four paradigmatic and connected case studies - the UK, Germany, Kenya and Tanzania - over time, including experiences of colonialism and decolonization, regime change, wartime and postwar reconstructions, and global economic transformations. In doing so, it asks how ideas about and policies on rights related to work have been articulated in different settings, over time, and how these have diffused globally, through interpersonal and international connections, new developments in international law and changing experiences of and expectations about the relationship between the economy, society and the state. It also reflects on the specific sociological contexts and connotations of ideas about socio-economic rights, including how women, ethnic and religious minorities, children and the elderly, have fitted into and shaped discussions and policies. To this end, GLOSOC brings together a team of historians based in the UK, Germany and Tanzania to uncover new sources, including oral histories, and connect sources that have previously remained isolated from each other, including archival records, mass media, policy documents and social surveys that reflect on socio-economic rights. It engages with these sources from a novel theoretical and methodological perspective. On the one hand, GLOSOC connects empirical historical research with social-scientific work on international norm diffusion and the development of human rights law, which has often been noted as laying the groundwork for thinking about socio-economic rights. On the other, it offers a genuinely global approach to the writing of global history through its collaborative and international research team. Not least, GLOSOC works closely with a selection of project partners around the world in order to make this research relevant and wide-reaching. These include local government and philanthropic agencies focused on issues of work and poverty; archives with a special focus in this area, whose work will be digitized and amplified through the project outputs, including the virtual exhibition; and, History & Policy, which will assist the project in making its historical findings relevant to current policy and practice. GLOSOC aims to benefit a wide range of users. These include academics in history and the social sciences, by publishing open access a co-authored monograph and top-ranked journal articles, as well as producing an oral history database and related conference and seminar papers. It will also benefit the broader public, through the creation of a virtual exhibition on the global history of socio-economic rights as well as through the project website that will feature regular blog posts from project members, including the international advisory board as well as guest authors. Not least, it will benefit external stakeholders through running two policy labs and writing two policy papers that reflect on how history can inform our understandings of and work with contemporary problems related to work and associated poverty.

UKRI Gateway to Research · FY 2024 · 2024-09

Proteins do most of the work in biological systems. They form the enzymes that catalyse all the reactions that occur, with remarkable selectivity and rate enhancement; they transmit signals; they form most of the structural components of the cell; they form the immune system which defends us against attack. In order to do this, they need to interact with a wide range of other molecules, for example enzyme substrates, signalling molecules, and other proteins in molecular complexes. When they do this, they change their shapes in relatively minor but functionally important ways. For example, a loop of polypeptide at the edge of the protein may change its orientation in order to bind better, or to shield an enzyme substrate from water. A particularly important example is that as far as we can tell, every enzyme changes its structure slightly when it binds to its substrate: this is often called the induced fit (or conformational selection) model. The significance of this example is that if we want to find inhibitors or allosteric modulators of enzymes, it is often the case that the most selective such molecules (and thus the best pharmaceutical drug targets) turn out to be those that bind not to the "relaxed" conformation of the enzyme but to the activated state. The problem is that it is often not easy to identify what these states look like. The normal ways for determining the structure of a protein are X-ray crystallography, or recently the AI program AlphaFold, which is designed to predict structures that are very close to the crystal structures, and does it very well. Both of these will typically find the relaxed state, but are less good at identifying activated states. This means that for many proteins, we know what the relaxed state looks like, but we have almost no idea how many other alternative states there are, or what they look like. This proposal uses an alternative method, namely NMR. NMR is the little brother of crystallography: it is slower and typically less accurate. However, it has two big advantages: it operates in solution (not in the crystal); and what you see in NMR is what is there, as an average. So if we can tease out the constituent structures from the averaged NMR data, we can work out what conformations are present, and therefore start to target them. This proposal sets out to do this. The novelty in the proposal comes from two directions. First, we avoid a lot of the most tedious and time-consuming parts of NMR structure calculation by starting with the AlphaFold prediction. Second, we propose a different way of comparing structures to experimental data, which gets round most of the technical difficulties in previous methods, and is called the NOE R factor in this proposal. It is a better method than current approaches because it provides much stronger discrimination between right and wrong structures. We have selected four proteins for study, which are all known to have alternative structures of different kinds. We propose to develop a semi-automatic pipeline for analysis, with minimal user intervention, which produces a detailed list of the structures present in solution. The most exciting aspect of the proposal is that there is currently no protein for which we can confidently say that we know what conformations it can adopt, or even how many different structures exist. This proposal will generate this information for four proteins, and thus for the first time allow us to start making some general rules about what conformations may be present for any protein, and in what proportions. We expect that this will encourage the design of novel inhibitors and allosteric effectors that bind to activated states.

UKRI Gateway to Research · FY 2024 · 2024-09

Enterococcus faecalis and Enterococcus Faecium are bacteria that cause human disease, including urinary tract infections, bloodstream infections, inflammation of the heart lining and valves, and even meningitis. Enterococcal infections can be hard to treat, due to limited choice of effective antibiotics, and increasing resistance to those antibiotics that are available. The emergence of multi-drug resistant strains of Enterococcus faecium has led to ~50% of infections in some hospitals now being resistant to the important antibiotic vancomycin. These resistant strains are associated with 2.5-fold increased mortality compared with sensitive strains, so new antibiotics targeting these bacteria are critical. Currently, only an estimated 40 targets are exploited by antibiotics towards all bacterial pathogens, and of 45 new antibiotics in clinical development, only 11 belong to novel classes. Identifying new targets for antibiotic development has been historically difficult, but one avenue for identifying new targets is to harness natural predators of bacteria, viruses called bacteriophage. Bacteriophages are viruses that can kill bacteria in a very specific manner. They can be isolated readily from the environment, including from wastewater and the soil, and are constantly co-evolving alongside the bacteria they infect. Bacteriophages first attach to their host by recognising specific molecules on the outside of the bacteria and then insert DNA into the bacteria in order to replicate. This DNA encodes for an array of proteins, some of which are involved in hijacking the bacteria to divert energy expenditure and resources to produce more virus particles rather than normal cellular processes. Despite the importance of bacteriophages and their encoded proteins for hijacking bacteria, around 70% of proteins encoded by bacteriophages have no known function. Some bacteriophages have been shown to produce proteins that are toxic to bacteria, and further, small molecules designed to mimic the function of these proteins have been shown to also be toxic. Many proteins encoded by these phage function by binding to proteins within the host cell, and preventing or redirecting their normal function. Therefore, the characterisation of phage proteins and the interactions they form within Enterococcus cells will provide information about new targets available for the development of new classes of antibiotics. In this research programme, I will identify phage proteins that are able to kill Enterococcus faecalis and Enterococcus Faecium. This will be combined with mapping out the 3D atomic arrangements of these phage proteins with X-rays and high-energy electrons (cryoEM). This combined approach will inform the mechanism by which phage proteins can kill bacteria, and be used in order to find new targets for antibiotic development. The University of Sheffield's recent £10M investment in imaging infrastructure, including state-of-the-art cryoelectron microscopy (cryoEM) and light microscopy facilities, will allow me to study phage proteins in unprecedented detail. Newly developed techniques, combined with the 'resolution revolution' in cryoEM allow for these proteins to be studied in a near-native environment, where cells infected with phage are broken, and the cellular contents are used as a basis for structural study. As well as forming a solid foundation for the design and engineering of novel antibiotics using my established expertise in targeting proteins with small molecule inhibitors, more information about phage proteins with no known function will also inform the design and engineering of bacteriophage for whole virus treatments, by giving us new tools for improving the virus's ability to infect its prey.

UKRI Gateway to Research · FY 2024 · 2024-09

Food security is one of the most pressing challenges that humans will face this century. A growing population, shifting dietary habits and a changing climate are placing unprecedented pressure on crop production. Future crops must therefore be resilient to climate change and (a)biotic stresses. Whilst modern crop varieties have been bred for high yields, this has led to a reliance on a diminished number of crop species and varieties, resulting in a vulnerability to pests and disease and a changing climate. Leveraging the genetic diversity that exists across different crop cultivars and landraces offers an opportunity to sustainably increase food production and close yield gaps by ensuring that crops are optimised to current and future environments. However, identifying the molecular mechanisms that underpin crop physiological responses to environmental stress is complex. Crops express phenotypic traits according to interactions between their genomes, the environment and how they are managed. Identifying how a given crop cultivar will respond to different environmental conditions is key to guiding breeding programmes. Phenotyping studies are underpinned by testing how crop genomes respond to environmental conditions, and how these conditions affects overall yields and the resilience of the crops to stress. However, this is resource intensive and limited in scope by the time and environment that the crops are grown under. There is a critical need to harness novel remote sensing techniques and state-of-the-art modelling approaches to model how genetically-regulated crop biochemical, structural and physiological traits affect yields, under different environmental scenarios. Closing this genotype to field-scale gap requires robust scaling methodologies that can be deployed at high throughputs. Leveraging our understanding of genetic controls on physiological traits and fluxes will enhance our ability to predict how crop genomes will respond under different environmental conditions.

UKRI Gateway to Research · FY 2024 · 2024-09

The Fellowship activities focuss on an underexplored but vital aspect of rural and urban economies and working-class livelihoods: sheep slaughterhouses, and in particular, halal slaughterhouses. The production of halal meat is frequently depicted in public discourses as culturally incompatible with British values, legitimising anti-Muslim sentiments. By exploring the complexities of halal sheep meat economies, and the everyday relations between the multi-ethnic workers who labour in them, I reassess media, political and academic explanations about the economic and cultural drivers of increased anti-immigrant and anti-Muslim sentiments in multicultural settings in Britain. Halal slaughterhouses sustain British rural sheep economies. They also offer employment to white British skilled slaughtermen who would otherwise be suffering the impacts of the corporate control of the slaughter sector, including deskilling and deleterious labour conditions. As such, these workers push back against claims that immigration has "left the white working class behind", or that immigrants have "taken their jobs." In theory, this should disrupt the economic and cultural factors which have been invoked to explain anti-immigrant or racist attitudes. My research is based on rare ethnographic access to three sheep slaughterhouses between 2019 and 2021, including two which slaughter through halal methods in both rural and urban locations. It focusses on the livelihoods and identities of multi-ethnic white British, British South Asian, Pakistani and Polish slaughter workers. I demonstrate that the absence of the purported economic and cultural causes of racism did not lead to an absence of everyday racism driving division and inequality between workers. In response to this paradox, I pay close, ethnographic attention to how classed, racialised, religious, gendered and national differences were invoked by slaughter workers to construct hierarchies in the workplace. I show that racisms emerged in relation to how white slaughtermen have themselves been stigmatised in Britain. Further, that anti-Muslim racism created a sense of solidarity between white British and white Polish workers. The research therefore offers unique insights into the changing forms of racism and allegiances forged in multi-ethnic work settings against changing flows of migrations to Britain. The Fellowship activities are centred on the consolidation of the doctoral research. Primarily, through journal articles and a monograph book proposal which will collectively explore themes of racism, Britishness, whiteness and class through the original lens of halal meat production. I will focus on engagement with the farming and slaughter sector, sharing my findings on racism in the workplace and its impact on labour shortages. Alongside this, I will focus on developing relationships with a racial equality think tank to inform anti-racism policy conversations. I will also produce an article for current affairs media audiences to challenge commonly held assumptions about halal meat. With a view to supporting my long-term career objectives to establish myself as an impactful researcher of racism in multicultural contexts in Britain, I will also carry out a pilot study, to inform an ESRC New Investigators Grant bid for a PhD related research project on high street halal butcher's experiences of racism in superdiverse urban contexts.

UKRI Gateway to Research · FY 2024 · 2024-09

Precision measurements lie at the heart of science and technology, and the development of more efficient estimation techniques will lead to new scientific discoveries and will push the boundaries of what is technologically possible. Potential applications include imaging, timing, navigation, bio-sensing for healthcare applications, radar and ranging technology, as well as traffic control and infrastructure monitoring. In several areas we are reaching the physical limits of noise reduction, and we have to contend with the quantum limits of measurement precision. By developing the mathematical tools for precision measurements in a quantum-mechanical setting we can open up a new field of quantum precision measurements. Our aim is to develop new bounds on what Nature allows us to learn about her, taking into account the practical considerations of limited data and the need for adaptive measurement techniques. In other words, we change how we interrogate the system based on what we have learned about it in previous measurements. We will investigate this topic in the context of the imaging of distant objects, with direct utility in the study of star formation and the hunt for exoplanets, where light tends to be faint and every photon counts.

UKRI Gateway to Research · FY 2024 · 2024-09

This fellowship can help my transition from a PhD candidate to an early career researcher and supports my application for the competitive Leverhulme Early Career Fellowship. In the longer term, it contributes to establishing myself as an expert on housing financialisation and immigrant housing. Four interconnected objectives underpin my academic ambitions: (1) Strengthening Academic Impact: Two journal articles based on my doctoral empirical data will be submitted as an extension and consolidation of my PhD academic contribution. My PhD research focuses on the financialisation and transformation of the unique immigrant housing in Taiwan, the Military Dependents' Villages (MDVs). These villages have been demolished, relocated, reconstructed, and privatised since the 1970s (Kuo, 2005). The first article will centre around the changing and mutating political informality during the MDV housing transformation processes. The second article will analyse the long-term housing (im)mobility of immigrant communities. I will attend two academic conferences to share my preliminary work. The support of this fellowship would bolster my academic profile by producing an emergent publication record. The ample resources allow me to develop influential research and academic networks, which is crucial in securing the prestigious Leverhulme ECF. (2) Striving for the Leverhulme ECF: This fellowship can help me develop my own research agenda and refine the application for Leverhulme ECF. I aspire to historicise and reconceptualise financialisation in East Asian developmental states in the three-year timeframe of the Leverhulme ECF, providing interdisciplinary integration across regional cultures, economic geography, political economy, regional conflicts, and urbanisation. Three years of Leverhulme ECF provides a means to develop my academic impact, and can establish my identity as a housing financialisation expert and strengthen my academic profile. (3) Enhancing My Qualitative GIS Skills: This fellowship will allow me to enhance my Qualitative GIS skills. The application of Qualitative GIS was developed in my PhD thesis and is mobilised in the Leverhulme application. Unlike traditional geospatial analysis, Qualitative GIS integrates different forms of data (qualitative and quantitative) with spatial information (Cope & Elwood, 2009), presenting more coherent and comprehensive spatial biographies. It facilitates the huge potential of knowledge exchange, linking MDV spaces with the stories told by residents, and documents and presents the histories collaboratively through visualisation. This year of knowledge and technical learning will equip me with the transferable skills to explore the connection between socio-economic phenomena (e.g., financialisation) and space in innovative ways. (4) Enhancing My Impact Beyond Academia: I will engage with a wider audience through cooperation with relevant communities (MDV communities and a troupe), transforming and disseminating my academic findings related to financialisation and the MDVs. I will host a workshop and invite MDV communities and relevant stakeholders to participate. The preliminary outcomes of Qualitative GIS built on fieldwork data will be presented, sharing derived information and this innovative approach to retell and preserve memories and knowledge of the MDV experience. In March 2024, I cooperated with a troupe in Seattle, which was interested in depicting the post-war daily life of MDVs. I will continue to support their exhibitions and performances by sharing my resources and networks, which contribute to strengthening the cultural cohesion of the North American Chinese community. I am committed to long-term collaboration with the MDV communities which will expand my impact beyond academia, and build partnerships of great potential in supplementing future related research.

UKRI Gateway to Research · FY 2024 · 2024-09

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

UKRI Gateway to Research · FY 2024 · 2024-09

Regenerative biology is a scientific field that aims to understand the mechanisms and limitations of regenerative capacity in different organisms. Although mammals are able to heal wounds and regrow many tissues such as skin and muscle, the regeneration of complex structures is limited to the liver, kidney and the tip of a finger. Aquatic vertebrates on the other hand, are able to regenerate large portions of organs and appendages including the limb, tail, spinal cord, retina and heart. When comparable damage occurs in mammals, tissues fail to regrow and scarring occurs. Organ regeneration in aquatic vertebrates requires many of the same genes that are deployed during the initial development of the organ. This indicates that the reactivation of developmental genes is an important step in rebuilding the organ. One possible explanation for the poor regenerative potential observed in mammals is that damage does not trigger these developmental genes. These genes are present in mammals but are simply not reactivated. Thus, the elucidation of the mechanism by which developmental genes are reactivated to restore missing tissue is crucial to further our understanding how successful regeneration takes place. Our project focuses of zebrafish as a model for regeneration. When a small portion from the end of the tail is removed, the fish regenerate the missing tissue after 3 to 4 days. This project will compare cell types present during tail development to those seen in regeneration. We aim to find out how similar tail development is to tail regeneration at the single cell and single gene level. The knowledge gained from our study may one day help us to develop new clinical approaches to organ regeneration in humans. Many of the same genes that are active during zebrafish regeneration are found in humans. This suggests that we may be able to activate the same pathways in humans to mobilise untapped sources of regenerative cells and improve our regenerative capabilities.

UKRI Gateway to Research · FY 2024 · 2024-09

Improving our current lifestyle and ensuring health of a growing population is reliant on the development of more advanced consumer products. Many of these engineered products have advanced functionality delivered by particles with nanometre dimensions, many thousands of times smaller than the width of a human hair. The exact size of these nanoparticles determines the mechanism of action and performance for the specific application. In healthcare, many drugs require encapsulation within polymer nanoparticles for several reasons, including for dissolving insoluble drugs, protecting drugs from unwanted degradation (e.g. mRNA vaccines) and providing efficient delivery (anti-cancer drugs). In electronics, the colour and intensity of light produced can be finely tuned by controlling the size of quantum dot nanoparticles, thus resulting in much higher quality displays, ultra-thin smart coatings (e.g. for wearable technologies), advanced diagnostics, high intensity medical imaging or high efficiency solar panels. The accuracy required to produce these materials is phenomenal and often only achieved reproducibly in dedicated research laboratories by specialist scientists. There has therefore been little progress on scaling up in a cost-effective or sustainable manner. In this project we will build platform technologies, comprising advanced chemical reactors underpinned by computational intelligence, which can scale up production of advanced nanoparticle products without loss in the precise control over structural dimensions which are achieved in research laboratories. We will build laboratory reactors which can be programmed to monitor the nanoparticle formation process in real time and relate conditions to the particle properties. Throughout the manufacturing process the machine learning algorithms will direct the reactors towards achieving the desired specification through 'self-optimisation' of conditions. A critical part of the project is then using the data obtained in the lab experiments to build a relationship between process and product which can be transferred onto equipment which can make the materials on a commercially relevant scale in a process called augmented lossless scale-up. We will take the optimised laboratory nanoparticle formation processes and demonstrate scale in several manufacturing environments, including R&D process laboratories and Commercial manufacturing facilities at our partners sites. Such demonstration will encourage further innovation beyond the lifetime of the project which can work towards realising advanced materials currently confined to research laboratories.

UKRI Gateway to Research · FY 2024 · 2024-09

The construction industry is facing problems due to its low productivity and the increasing shortage of skilled labor. It is thus essential to introduce automation and digital technologies in construction processes. The 3D-printed concrete (3DPC) technology is one of the digital construction technologies, seeing remarkable progress over the recent years. However, the durability performance of 3DPC has received less attention. The incorporation of reinforcement in 3DPC is essential for structural applications for load-carrying capacity, ductility, and robustness. The chloride-induced corrosion of reinforcement is one of the main durability problems, causing numerous casualties and substantial economic losses. However, the durability performance of 3DPC with respect to chloride-induced reinforcement corrosion has not been fully understood. This project aims to fully understand chloride transport properties, and corrosion mechanisms in 3DPC, and to develop corrosion protection techniques for 3DPC made with different printing materials (i.e., normal strength concrete and ultra-high performance concrete) and incorporating different types of reinforcements (i.e., steel bars and/or steel fibers). The chloride transport properties will be studied by exposing specimens to chloride environments through a wetting-drying process and determining chloride contents, including free, total, and bound chlorides, chloride diffusion coefficient, and chloride binding capacity. Corrosion specimens exposed to various chloride environments will be investigated by corrosion potential and corrosion current density measurements. Finally, the currently available corrosion protection methods developed for cast concrete will be investigated for 3DPC. The findings will be used to develop design recommendations to enhance the corrosion free life of reinforced 3DPC structures. The outcome of this project will boost the safety, durability, and service life of reinforced 3DPC structures.

UKRI Gateway to Research · FY 2024 · 2024-08

Uganda is situated between the Eastern and Western branches of the East African Rift system and is prone to moderate level seismicity causing several destructive events in the past. Currently, seismic risk in Uganda is increasing at a fast pace due to high population growth, rapid urbanisation and vulnerable building stock caused by lack of building regulations and expertise for designing and constructing earthquake resistant structures. Therefore, there is an urgent need (i) to characterise seismic hazard (including earthquake induces landslides) using new methods, (ii) to categorise structural systems of residential building stock, (iii) to determine the location and distribution of different building categories realistically at national level, (iv) to assess their expected performances, (v) to determine seismic risk, and (vi) to develop risk reduction and management strategies. However, assessment and management of seismic risks in Uganda is a big challenge due to limited data availability, lack of expertise and insufficient resources. This project brings together a partnership of researchers from the University of Sheffield in the UK, and Makerere and Kyambogo Universities in Uganda, for the first time, to address the challenge faced by Uganda. The assembled research team will work towards the achievement of ambitious objectives of the project in close collaboration to reduce future earthquake related loses and develop more resilient communities in Uganda against seismic events. The project team will actively engage with governmental and non-governmental agencies in Uganda (such as National Bureau of Standards, National Building Review Board, Engineers Registration Board, Institution of Professional Engineers) to understand needs within the country, disseminate project outputs widely and maximise impact. Meetings with key policy makers will be held to examine potential areas for future development of the Seismic Design Code and risk management tools, to discuss barriers to change, and to develop proposals for change. Presentations to local communities will also be carried out to understand their current awareness of seismic risk and mitigation measures and to gather feedback on the accessibility and acceptability of the proposed changes and developed tools. The project will also train next generation of researchers, academics, practitioners, engineers, PhD and MSc students in Uganda by organising free online courses to equip them with necessary knowledge and skills in the fields of seismic design, vulnerability, risk and resilience.

UKRI Gateway to Research · FY 2024 · 2024-08

The richest 1% of the world's population now own more than half of the world's wealth. In this context of extreme and growing levels of economic inequality, we need to 'study up' and examine the role of wealth and wealth holders in creating, reproducing and entrenching inequalities across the globe. However, few studies have yet been able to examine how elites integrate at a global level. This project seeks to identify the role of elite business communities that work within and across the global North and South as they build alliances and circulate ideas, people and capital to shore up advantages. It will do so through an international multi-sited study of three elite organisations and their members. The project will examine three of the leading international business communities in terms of their global reach and their members' economic influence. These organisations are known to run educational and training programmes and to connect economic elites globally, with varying requirements in terms of the minimum revenue of member's companies and the minimum number of employees. The companies run by members of these three organisations employ millions of people and have a combined revenue of trillions of dollars annually. The research will focus on these key organisations in order to better understand two key questions in relation to global elites. First, it will examine the concrete practices through which international economic elites forge alliances and whether this evidences their potential emergence as a class or identifiable group. Second, it will explore the various mechanisms through which these organisations create and reproduce advantage among their members. The project will focus on key elite formations and networks in three urban contexts, Delhi, Johannesburg and London, chosen in order to cover existing and emerging wealth centres. It will pioneer a multi-sited study of elite international business communities in the three cities, comparing their elite formations and mapping the transnational connections between their members. Such insights can help us understand the role these business communities, and related elite organisations that facilitate social or business networks, play in a global architecture that sustains and grows wealth and other key inequalities. Knowledge about how to understand, and thereby more effectively challenge, wealth inequalities is more needed than ever. The existing research on the role of intensifying concentrations of wealth at the top, including by the PI, has provided evidence that economic elites are key engines in the reproduction of inequalities, whether securing the preservation and growth of dynastic wealth with the aid of financial professional intermediaries, or gaining influence through political donations to create a favourable institutional environment. By focusing on three leading international business communities and their networks, the research will allow us to see how ideas, people and capital circulate among some of the wealthiest owners and managers of corporations in the world. The project has been designed in close collaboration with the United Nations Research Institute for Social Development (UNRISD), a research institute that analyses the social dimensions of contemporary development issues, with the aim of analysing global elite networks and their repercussions for policy. The UNRISD will co-host an international workshop for civil society practitioners, policy-makers and academics at the Southern Centre for Inequality Studies in South Africa, and support associated outputs from that event, including a policy-briefing note and blog piece. The project findings will be used to develop further data, tools and strategies for civil society to shape political debate, hold corporations to account and inform the public about elite power, global elite networks and inequalities.

UKRI Gateway to Research · FY 2024 · 2024-08

Our bodies are composed of precisely arranged organs and tissues. However, it is still unclear how they form during the earliest stages of life in the embryo. A pioneering concept is a process called 'positional information' that largely arose from work on the developing chick limb. This involves different regions of the embryo being assigned a positional value, rather like how places on a map are given a set of coordinates. Cells receive information about their position by signalling molecules produced by other specialised groups of cells called organisers. Cells then encode this information and use it to develop into different tissues and organs. Our hypothesis is that cells in the developing chick limb have their positions encoded by being able to compare how similar they are to neighbouring cells - thus cells that make the digits tend to adhere more to each other than they do to cells that make the elbow. We will determine how one protein - called N-cadherin - is distributed along the limb in a graded manner to encode cells with different adhesive properties (e.g., elbow or digit). Knowledge of how cells encode their position in the limb could be used in regenerative therapies in the future. Thus, if a limb is amputated, cells need to know their positional identity to replace the correct missing structures.

UKRI Gateway to Research · FY 2024 · 2024-08

Eighty per cent of pharmaceutical interventions fail in patients even after being successful in animal studies. Musculoskeletal (MSK) diseases such as osteoporosis (OP) reduce dramatically the quality of life of millions of affected patients. Mice are the most common animal model to test new treatments. Nevertheless, the extrapolation of their effect onto patients and the identification of which new treatments should be tested in clinical studies is based on simple scaling approaches. In this project I will develop a new mechanistic computational framework that bridges between mouse and human, informed by in vivo experiments in mice, to discover optimal treatments in patients. I will create two parallel virtual mouse and human twins (VMHTs-OP), based on similar inputs (biomedical images, cell data, gait data) that will predict bone adaptation in function of biomechanical and/or biochemical stimuli. Each virtual twin will be based on advanced multi-scale computational models (multi-body dynamics, finite element and cell-population models) to predict bone adaptation over time and space due to OP and to new biomechanical and pharmacological treatments, identifying in silico the new combined treatments that are likely to be effective in patients, to be tested in future clinical trials. The models will be going through a comprehensive verification, validation and uncertainties quantification process in order to provide the required credibility for future preclinical applications. The model predictions will be validated against longitudinal mouse experiments and available longitudinal clinical data from known biomechanical or pharmacological interventions. Finally, the validated framework will be used to test in silico several combinations of treatments regimens (overlap, intermitted, drug holidays) and different interventions (microgravity, high strain exercises) that would not be ethically nor economically testable in animal and clinical trials.

UKRI Gateway to Research · FY 2024 · 2024-07

Mass spectrometry (MS) is a critical analytical technology that underpins a significant research portfolio across the School of Biosciences at The University of Sheffield (TUoS). This research involves understanding biochemical pathways at a molecular level through the analysis of proteins and metabolites. The demand for more specialised and increased information from mass spectrometry has led to the need for investment in advanced technologies with enhanced capabilities above our current instrumentation. These limitations include depth of coverage (ability to detect less abundant biomolecules), amount of sample required for analysis, and lack of detailed spatial distribution information. The acquisition of this new instrument will enable a step-change in our ability to undertake sophisticated molecular analysis of complex biological systems aligned to the BBSRC remits of advancing the frontiers of bioscience discovery and tackling strategic challenges1. In particular targeting the priorities of bioscience for sustainable agriculture and food and understanding the rules of life. The objective of this initiative is to acquire the Bruker timsTOF fleX MALDI-22 mass spectrometer. This cutting-edge instrument provides superior speed and sensitivity compared to our existing equipment which facilitates a substantial boost in sample throughput for analysis. Furthermore, it boasts the capability for mass spectrometry imaging to measure the spatial localisation of metabolites or proteins within a tissue section. This dual functionality of determining both the "what" (identity) and "where" (spatial distribution) of specific metabolites or proteins provides valuable insights into the biochemical and cellular processes underlying biological phenomena. Existing technological limitations in spatial resolution for imaging mass spectrometry have posed a significant barrier to advancing our understanding of metabolism. The inability to measure the localisation of metabolites at a cellular level has been a major bottleneck. The advances in technology and the introduction of the timsTOF fleX MALDI-2 instrument has made single cell imaging a possibility with the ability to image routinely down to a level of 5µm. This improved resolution opens up a diverse array of research possibilities. The proposed uses of the instrumentation will serve key strategic BBSRC research priorities by providing advanced analytical technologies to researchers, at all stages of their careers, across TUoS and beyond. For example, a better understanding about biochemical pathways in agriculture allows us to find early biomarkers of disease or develop targeted pesticide or herbicide usage leading to reduced applications of these chemicals. It can also inform us as to the mechanisms of pollinator and pathogen interactions with plants and therefore how this can be managed in a more sustainable way. The advancement in the technology allows us to increase our capabilities in other areas within the BBSRC remit including bioscience for an integrated understanding of health by studying ageing and the immune system using a drosophila (fruit fly) model organism. Securing this equipment is essential for expanding the frontiers of our existing research portfolio within the BBSRC priorities.

UKRI Gateway to Research · FY 2024 · 2024-07

This proposal will fund a Refeyn TwoMP Mass Photometer, a transformative technology currently unavailable in Sheffield, hosted in the School of Biosciences (SoB) at the University of Sheffield (UoS) and accessible to researchers across the region. Mass photometry is a state of the art, single molecule approach for determining the size of molecular assemblies based on light scattering. All biological processes are underpinned by how different biomolecules (e.g proteins, lipids, nucleic acids or carbohydrates) interact with each other. Example applications in Sheffield cover the full BBSRC remit, ranging from the relatively simple to incredibly complex, such as a single protein binding a DNA target sequence or assembly of photoreaction centres for photosynthesis. The common feature of these fundamental biological processes is a change in the size, or mass, of the biomolecules involved. For such a simple concept, observing a change in the mass of a biomolecular assembly can be very technically demanding and time-consuming in the lab. Mass photometry is universally applicable, as all molecules scatter light, irrespective of their composition. This versatility means the instrument will benefit a vast array of research in Sheffield. To maximise the impact of the Mass Photometer, we will host the equipment in an existing core facility at UoS made available to researchers across faculties and external partners in the Sheffield region. The proposal has a number of clearly defined objectives: Provide a transformative technology, currently unavailable locally to Sheffield-based researchers, to prime new avenues for world leading research and revolutionise our research outputs. Align the technology infrastructure at UoS with evolving research priorities at a national and international level. Reinforce existing strengths in single molecule bioscience and technology development. Maximise the efficiency and throughput of existing cryoEM, structural biology and 'omics facilities by providing a rapid and simple method to assess sample heterogeneity and quality, which will integrate seamlessly into current workflows. Provide training in the latest single molecule biophysical technologies for graduate students on UKRI funded DTP programs, PGT courses and technical staff. Support closer collaboration between bioscience researchers in the Sheffield region, and aligning technologies for basic research on UoS main campus with translational manufacturing capabilities at the Gene Therapy, Innovation and Manufacturing Centre (GTIMC). The proposal will bring facilities at Sheffield up to date with the latest technological developments, ensuring that our research infrastructure is aligned with evolving research practices. It will promote equality of opportunity between different regions of the UK, by providing researchers in Sheffield access to technologies available in other leading UK institutions. As the instrument will be housed in an established facility in an accessible location, we will ensure strong management, high environmental sustainability and reach the widest possible range of users. We believe the proposal offers incredible value for money, an impact reflected in the breadth of research and number of applicants highlighted in this proposal, which will significantly boost the world leading research in the SoB (ranked 4th in REF 2021) and across Faculties at UoS and our project partners.

UKRI Gateway to Research · FY 2024 · 2024-07

THE CHALLENGE: Biopharmaceuticals are growing at a rate double of traditional pharma owing to the unique properties of microorganisms including their biocompatibility and technology that cannot be easily replicated in the lab. The UK needs to rapidly expand its biopharmaceutical manufacturing capacity in order to access a greater fraction of the global market and realise the economic benefits of job creation and exports. "Bugs as drugs" have been seen historically to treat diseases including cancer which is inspiring the next generation of treatment options for cancer patients, particularly those with chemotherapy-resistant, recurrent, or metastatic disease. However, a major challenge for use of "bugs" including bacteria and cancer-killing viruses is they are readily recognised by the immune system and rapidly removed before they can take effect. Our team wants to overcome this challenge through our research so that we can unlock the benefits for more patients, allowing all cancer to be treated with these therapies. The full potential of these medicines can only be realised by enabling their targeted delivery to tumours within the bloodstream whilst simultaneously bypassing the body's defence systems. To do this, we have successfully developed a number of nanocarriers for cancer-killing viruses. Due to their nature, these viruses are sensitive to degradation and elimination, however our bubble-like particles not only shield them for targeted delivery, but the packaging is done in a way that maintains the viruses viability and functionality - the first time this has been shown. Synthetic alternatives (e.g. polymers) are incompatible with biological therapies due to exposure to harsh conditions (heat, solvents, pressure) during production as well as being known as highly inefficient. OBJECTIVES: Here, we focus on materials derived from natural sources (e.g. plants) that are non-toxic, biocompatible, sustainable and biodegradable. Utilising the 'safe and sustainable by design' (SSbD) framework, a voluntary approach to guide the innovation process for chemicals and advanced materials as recommended by the European Commission, we will scale-up the manufacture of our bioinspired nanocarriers to be 'clinic ready'. The scope of experiments required to optimise these systems requires high throughput microfluidics which we have developed 'in house'. Our microfluidics device can rapidly mix and produce high quality nanoparticle encapsulated viruses at large scale with the promise to outperform current commercial devices. We now want to optimise our device and consider improved mixing speed, reproducibility, productivity/scalability as well as reduced cost. BENEFIT: So far, biological therapies have not lived up to their potential due to their poor delivery in the body. Here we present a sustainable solution to scale up new modalities for the treatment of all cancers by formulating them within bioinspired nanoparticles, specifically designed to maintain the functionality of these sensitive biological agents and provide targeting capabilities. This innovative project fully aligns with the EPSRC core theme for the development of a pipeline for controllable, reproducible, and scalable production of our bioinspired NP platforms to facilitate clinical translation and unlock the power of biological therapies. This will have applications across the growing biopharma market where low therapeutic index, immunogenicity and lack of scale-up are major barriers to entry for these therapies. Whilst we use viruses as an exemplar, our platforms can be used to package any drug/agent (e.g mRNA) for wider clinical application.