2775728Grey Milk and Lost Kin: Re-sounding, Re-visioning, and Re-membering Trauma in the Scottish Gypsy Traveller ArchivesClosedStudentshipAHRCResearch Management"We have no right to any form of writing, that is our curse," proclaimed a 1950s Gypsy Queen (Lecouteux 2016, p.6). This research transforms the curse of "internalised oppression" (Davis 1981) as my ancestors incite an uprising by way of the archives. My practice-based research aims to retrieve and revalue "subjugated knowledge" (Foucault 1980) through critical archival interventions, place-based approaches, experimental filmmaking and literary practices. I will interrogate the absence and rupture of 'knowing' caused by forced assimilation and cultural dispossession, exploring the sociocultural impacts of knowledge suppression and its far reaching mechanisms of denial. Grounded in lived experience, this study adds to urgent scholarly work seeking to transform the cultural ramifications of colonial legacies which actively erase Indigenous and Local knowledge systems, their cultural heritage, and collective identity. My family avoided persecution by keeping our genealogy secret and disavowing our Scottish Gypsy Traveller ancestry.From the mid twentieth century onwards, vast institutional archives were amassed in Scotland of the travelling peoples' oral traditions. Newly accessible online since the pandemic, I will subvert these archives to activate the affective, cultural and experiential injuries of "racial capitalism", drawing out the traumatic traces of invisibility and exclusion (Gordon 2008). I will then reframe and valorise the Gypsy Travellers' knowledge system, building power relations through "re-citation" with other subjugated cosmologies. Finally, I will undertake an intersectional exploration emphasising the feminist and decolonising interventions of re-sounding, re-visioning and re-remembering, mobilising solidarity and liberatory consciousness to counteract "epistemic violence" (Galván-Álvarez 2010).Thus, I will create a body of work, including film, art and audio works, that act as "a counter-archive of knowledge"-underpinned by Indigenous narrative and listening strategies (Horavoka 2017). In this way, my research will contribute to experimental sonic and cinematic techniques and methodologies, whilst generating critical pathways that pluralise knowledge systems more widely.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified2642845Medical diagnosis through the application of Artificial IntelligenceClosedStudentshipOther NPIFSch of ComputingThis project will look at some aspect of medical diagnosis through the application of Artificial Intelligence which will be determined in more detail by the end of year one6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified1907672DNA methylation age acceleration: examining the role of socioeconomic position and dietClosedStudentshipESRCEpidemiology and Public HealthThis project proposes to investigate whether socioeconomic position is associated with DNA methylation in the MRC National Survey of Health and Development (1946 birth cohort), and whether indicators of diet might mediate any associations found.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified10057221A modular sea lice removal system utilising electro-anaesthesia, low-pressure pumping and waterjets to gently remove lice without inducing stress and compromising fish welfare.ClosedEU-FundedHorizon Europe GuaranteeElectrolicer will be the first system that can combine sea lice removal with fish welfare during treatment. The system has been designed by Ace, a company with extensive experience in electro-anaesthesia. Water is inserted into the pipeline to create suction that draws fish calmly from the cage into the tube. Electrolicer then holds the fish in a calming low-voltage electric field that relaxes the muscles, and low-pressure water gently removes lice and eggs. Electrolicer also reduces expenses associated with adopting this technology. The solution can be used on an existing, generalised work boat, instead of requiring the purchase of a dedicated sealice removal vessel. By avoiding chemicals and favouring multi-modal treatments within the system, Electrolicer also addresses treatment resistance in lice. Ace is backed by sustainable investment group Aqua-Spark, whose mission is to invest in companies using technology to improve sustainability in aquaculture6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified906CF747-4235-4D89-9315-DDA1C2E047C0ACE AQUATEC LIMITEDLEAD_PARTICIPANT1560910.01092637.0ES/S001875/1Social and Economic Implications of Transport Sharing and AutomationClosedFellowshipESRCSchool of Social & Political SciencesThis study will link the changing nature of jobs due to automation and the platform economy to regional infrastructure planning and transport operations, and the role specifically of transport automation within this context. The patterns and forms of jobs are changing due to many different reasons, leading to non-traditional work schedules and differences in commuting patterns, non-standard work travel patterns, and even elimination of certain jobs and creation of new ones, with significant implications for regional infrastructure planning and transport operations. At the same time, there are enormous changes anticipated in infrastructure and operations, due to large-scale automation in the transport sector (eg autonomous and connected vehicles). This project will make estimates of the changing nature of jobs due to these considerations at the regional level towards the goal of deriving the transport and regional infrastructural planning consequences. The project will use labour market survey data as well as privately-held labour market data on jobs, skills and industry to estimate regional variations due to these trends, given regional industry-occupation mix. These changes will be linked to the Spatial Urban Data System (SUDS), which is a UK-wide geospatial data infrastructure under development within UBDC containing transport infrastructural and operational conditions. , and which has been recently used to identify areas of transport poverty throughout the UK and the extent to which and which we will expand through work with the project's industrial partners. Using these data sources, we will identify regional automation risks due to unique industry and skill concentrations and derive transport and infrastructure planning implications. Within this context, we will also evaluate the role of autonomous vehicles given potentially different commuting patterns using specialist transport simulation models. We will further develop specialist transport simulation models to ascertain which packages of "last-mile" transport solutions (low-energy station cars, autonomous vehicles, shared transport, active travel and demand-response services) are likely to bring about high-quality, sustainable and socially-equitable forms of transport accessibility in areas at risk of changing nature of jobs. We will then combine the results of our various model scenarios, using ensemble forecasting methods utilising Bayesian Model Averaging or related techniques to ascertain which packages are more likely to bring about high-quality transport accessibility in the selected areas.With 66% of the world's population estimated to be living in urban areas by 2050, the need to provide new transport infrastructure and to address traffic congestion, road fatalities, air pollution, and associated problems continue to generate debates in policy circles. Impact on local economic development and labour market planning: The work related to estimating the potential impact of automation and AI on jobs given skills required in the occupation-industry mix regionally available is likely to be of immense value to regional infrastructure planners and business owners, as well as for skills-development initiatives and organisations in the local economic development planning. Through UBDC's networks, we will engage local authorities and other stakeholders in co-creating our results on this topic, so as to involve our work in their planning processes. Transport and infrastructure planning and operations impact: Additionally, there is a range of shared technology, automation and use of AI and Machine Learning (ML) being proposed in transport, and a growing business community involved in their development and use. Although the trends surrounding automation and sharing transport are being driven primarily by private companies, governments around the world are increasingly developing policies to support as well as to regulate many of these developments, and the UK government has an active programme on Connected and Autonomous Vehicles (CAV); among the high-value economic infrastructure to be funded through the 2016 National Productivity Investment Fund (NPIF) is £390 million for future transport including ultra-low emission vehicles and CAVs. Additionally, various types of shared mobility services, e.g., car-sharing, dynamic ride-sharing, on-demand personal mobility vans, and express, crowd-sourced urban delivery services, under the banner of Mobility-As- A-Service (MaaS) are now offered by private companies in UK cities. Just as the introduction of the private car in the beginning of the twentieth century transformed the way we live our daily lives and the ways in which cities developed, large-scale automation, connectivity and sharing of mobility resources (sharing economy) are expected to be a step-change changing daily lives in future society and the form and functions in cities.We expect that our results will help highlight significant regional planning and operations impact of such technology, against the backdrop of changing commuting and work-related travel patterns resulting from the changing nature of jobs. Industrial Impacts: The approach will allow us to evaluate spatial and regional effects of varying degrees of automation and sharing mobility, and to identify new markets in smart cities and urban planning. Our industry partner, Peter Brett Associates, views that the risks of emerging technology being left out of the planning agenda are great due to lack of empirical data, leading technology disruption in transport to occur in an ad-hoc way. Having the results of the analysis and the associated data would help them reach new markets and also to reduce uncertainty in their forecasts. Scottish MaaS, has similarly noted that the methods and results being proposed will help them reach new markets both geographically thereby opening up UK companies to a global pipeline of contracts in integrating CAVs into infrastructure planning and construction, and MaaS solutions in addressing expensive last-mile problems facing city managers worldwide.FA3D6B2E-20C9-4738-A451-89FBB11592A0Electrical engineering16D7B3C750-5146-47F0-B10D-145C65C76B3BCivil eng. & built environment56184898E4-BFA4-4527-9835-7EB4EC158219Science and Technology Studies161908FDF5-1C61-4F33-B47F-3E91675C88AAInfo. & commun. Technol.8184898E4-BFA4-4527-9835-7EB4EC158219Science and Technology Studies16990813BA-F64D-4C20-BF55-5D96210DAA9EArtificial Intelligence8FD031323-3ED1-42EC-84FE-AF21AA5B607FRobotics & Autonomy16F6DFE439-6799-42C8-8C33-ABDFBBE848A0Transport Ops & Management562119089Microbial Interactions Within Denture BiofilmsClosedStudentshipBBSRCDentistryMost microorganisms naturally grow within biofilms in both environmental and industrial systems. Biofilms on denture surfaces are widely acknowledged and arise in cases of poor oral/denture hygiene and where dentures are not removed whilst sleeping. Key microorganisms in denture biofilms include fungi of the genus Candida as well as bacteria that can originate from other oral sites or from exogenous sources. The majority of denture biofilm studies have targeted Candida as these fungi are highly adept at adhering to denture acrylic and can induce the infection, denture associated stomatitis. Denture biofilms are, however, ideal for investigating microbial interactions since they are readily accessible, polymicrobial and variable in their microbial composition and can be modelled in vitro. Furthermore, difference in conditioning of the denture surface may also lead to differential species colonisation and biofilm behaviour. Preliminary studies in our School of Dentistry have highlighted the effect that bacterial species may have on denture biofilm composition and behaviour of Candida albicans. We have found that Candida growth can be inhibited in biofilms by Pseudomonas aeruginosa, whilst other bacteria, such as certain streptococcal species can influence the morphologyof C. albicans. The reasons for these effects remain unclear, but could be due to specific associations between species, or a feature of a wider community effect on the biofilm. Project aims The aims of this PhD are therefore to explore the types and mechanism(s) of microbial interactions that occur in biofilms, using denture biofilms as model systems.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified750553Safe and Sound - secure and sustainable Cloud3D servicesClosedVouchersInnovate UKSafe and Sound will enable Hao2.eu to research and develop good practise standards and approaches to deliver secure and sustainable Cloud3D services which proactively anticipate and support the needs of vulnerable groups such as people with autism and learning disabilities.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified288A0B86-D107-4599-8CC3-167C05AF1D49HADWEBUTKNOWN LIMITEDLEAD_PARTICIPANT5000.05000.0NE/H526886/1Doctoral Training Grant (DTG) to provide funding for 3 PhD studentships.ClosedTraining GrantNERCSchool of Life SciencesDoctoral 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.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedNE/L011956/1Undestanding microbial communities through in situ environmental 'omic data synthesisClosedFellowshipNERCCollege of Science and EngineeringThe purpose of this research is to integrate different sources of 'omics data in environmental science for microbial community analysis. The computational based comparative analysis of DNA sequences may provide information about genome structure, gene function, metabolic and regulatory pathways and how microbial genomes evolve. However, to fully delineate microbial activity and its response to environmental factors, it is necessary to include all levels of gene products, mRNA, protein, metabolites, as well as their interactions. I propose to use large-scale whole genome metagenomic sequencing for assessment of taxonomic and functional diversity of microbial communities. The data generated by metagenomic experiments are both enormous and inherently noisy, containing fragmented DNA sequences representing as many as thousands of microbial species. After using pre-filtering steps, including removal of redundant, low quality sequences, the short DNA sequences are assembled together into longer contigs of overlapping reads, and these contigs may then be scaffolded into full genomes in a bottom-up approach. Having obtained the assembled contigs, the obvious next step is to use publically available databases to annotate the coding regions in these contigs. This will tell us WHAT functionality is available and provide information on WHO is there, the metagenomic sequences are binned, i.e., by associating a particular sequence with an organism. This can be done by either searching for phylogenetic markers or by looking for similar sequences in existing public databases. The end result is the community profile of different samples in terms of organismal abundances within each sample. Whilst metagenomic analysis gives a profile of the microbial community at a specific place or time, and their potential functional, it does not reveal which genes are actually being transcribed. I thus propose to integrate sequencing-based metatranscriptomics in which total RNA (a proxy for gene activity) is extracted from microbial community, converted to cDNA and sequenced without the need for cloning. This will provide information on the regulation and expression profiles of complex communities by enabling quantitative measurements of dynamic expression of RNA molecules and their variation between different states reflecting the genes that are being actively expressed at any given time. However, the story is still far from complete, as we do not have direct evidence of the metabolism within a cell. To give a more complete picture of living organisms, I will integrate metabolomics which will provide unique chemical fingerprints that are a function of specific cellular activity. In particular, the focus will be on identifying habitat-specific endogenous and exogenous metabolites along distinct geochemical conditions. These metabolites will be detected using two-dimensional gas chromatography coupled with mass spectrometry. They will be related to the expression levels from transcriptomes using information on metabolic pathways readily available from annotating metagenomic sequences. In this way we will integrate all three sources of information, mapping the metatranscriptome onto the assembled annotated metagenomes and reconciling the reconstructed metabolic pathways with observations on metabolite concentrations and fluxes. From this we will be able to predict the metabolic function of the entire community not simply who is there.The removal of complex organic contaminants from soils will be one of the major environmental challenges facing the United Kingdom over the coming decades and recommendations based on this proposal will be of use to stakeholders especially, the remediation consultants, industry regulators i.e. SEPA and local councils. Brownfield development is an important part of the societal shift towards sustainability. Many contaminated brownfield sites sit unused for decades because the cost of cleaning them is more than the land would be worth after redevelopment. This research will impact on our ability to achieve sustainable reclaim of environmental capital and will allow adaptive re-usability. The Earth Microbiome Project has generated an enormous collection of data with the intention of producing a global Gene Atlas describing protein space, environmental metabolic models, and characterizing a global environmental parameter space for microbial communities. This global environmental sample database is an ambitious initiative that is community-driven. The tools developed in this fellowship will exploit this vast amount of information to provide useful insights on the Earth's microbiome and to catalogue all the microbes that live on earth. This will be of great benefit to mankind as whole, these microbes are performing vital functions, and to environmental researchers. Methanogenesis is a key process in the carbon cycle, methane is a more potent greenhouse gas than carbon dioxide, therefore understanding its metabolism at a community level is of fundamental importance if we are to incorporate microbial processes into models of climate change. Methane is an important greenhouse gas yet its production could play a part in the transition to a low carbon economy. Water treatment is the fourth most energy intensive sector in the UK and consumes approximately 1% of the UK's electricity. Reducing the energy required to treat wastewater would therefore have major benefits both by reducing costs and carbon dioxide emissions. Anaerobic digestion (AD) reactors have the potential to provide these benefits. They do not require the same energetically costly aeration as aerobic methods and through the action of methanogens produce biogas. Better understanding of methanogenesis could lead to more efficient AD reactors.4CCA4C04-0C28-41BE-8869-FA6391A7F005Microbial sciences2029F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies70F673FD2B-013B-47E5-9E62-03BAB1E7348EEnvironmental engineering10AF3F5E7C-7FB6-4588-9174-6018BA2A231BEnvironmental Microbiology20937A9F23-021A-4604-8979-A28E0E04F825Transcriptomics10513702B4-7C48-41F2-A1A0-8B4E8BEDCABCAssess/Remediate Contamination10C6A85141-ED79-4266-86E5-F6D25217C97FEnvironmental Genomics407E61B40B-93E5-4D69-8C89-426ED7E0D2B4Metabolomics / Metabonomics202430216Real-time prediction of cellular states in 3D lattice light sheet microscopyClosedStudentshipMRCWarwick Medical SchoolProgramme overview: This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project overview: Lattice light sheet microscopy (LLSM) is a new technology to visualise fast cellular processes at the time scale of 1 second, in 3D. LLSM is very low through-put however, limiting its use for studying rare events, such as cell divisions. In close collaboration with industrial partner Intelligent Imaging Innovations Ltd. (3i), suppliers of LLSM, we will develop an integrated imaging pipeline to classify and anticipate physiologically meaningful events during the cell cycle using state of the art machine learning. The main goal is to 1) enable automated control of the image acquisition and increase its throughput, and 2) make it possible to analyse statistically significant numbers of well-defined cellular events and their progression from an early stage, which often go unnoticed by even the most expert human experimenter. Enabling detailed spatio-temporal analysis of the 3D imaging data will help to better understand the timing and control of different stages of cell division and recognise more subtle defects in cell division which can affect development or diseases such as cancer where divisions occur uncontrolled. This is an interdisciplinary project at the interface of cell biology, computer science and engineering, enabling fundamental science to improve human health through world-class biomedical research. Health focus is enabling biological research into genetic risk and disease mechanisms, aiming at new strategies for early diagnosis and treatment. The specific training the student will receive is geared towards quantitative and interdisciplinary skills and understanding of whole organism physiology in addition to that of single cells in the main project. The training in advanced machine learning and computing addresses the demand for team scientists and technology specialists and will help to build new software technologies and imaging instruments that will become available to the biomedical community in the future.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified10117189Newton's CradleClosedDepartment for Science, Innovation & TechnologyInnovate UKA novel organisational model that addresses gaps in how we deploy, evaluate and leverage medical AI at scale, with a research-led methodology and an industrial focus.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedF739D642-26BA-4B54-8D13-A40E80D219F9NEWTON'S TREE LTDLEAD_PARTICIPANT100000.070000.010074740The University of Nottingham and Siemens Energy Industrial Turbomachinery Limited KTP 23_24 R1ClosedKnowledge Transfer PartnershipInnovate UKTo develop and implement a novel methodology, for rapidly analysing the heat transfer and flow performance of additively manufactured porous lattice structures within high temperature gas turbine applications.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified2EBCC169-13F8-4E3A-B92F-95BE8AC88DF6UNIVERSITY OF NOTTINGHAMLEAD_PARTICIPANT90000.045000.010067645REPOXYBLE: Depolymerizable bio-based multifunctional closed loop recyclable epoxy systems for energy efficient structuresActiveEU-FundedHorizon Europe GuaranteeMaterials, especially advanced materials, are the backbone and source of prosperity of an industrial society” (Materials 2030 Manifesto). The Green Deal and the Digital Decade establish high-priority policies for Europe, where 70% of all technical innovations are directly or indirectly attributed to advanced materials. Lightweight and high-strength materials have consistently played a key role in the construction of fuel-efficient and high-performing transportation structures. Lightweight materials such as glass and carbon fibres composites are commonly used due to their intrinsic properties such as high mechanical performance. However, the poor recyclability and recovery aspect poses a significant challenge. The end-of-life aspect of these materials is crucial, as when landfilled they release toxic substances into the environment. Moreover, minimising resource use, energy of manufacturing processes and optimising waste disposal of future advanced materials can help mitigate cost and product’s end-to-end footprint acrossits global lifecycle, thereby significantly improving its overall environmental performance. REPOXYBLE will create a new class of high-performance materials -bio-based epoxy composites targeting cost and energy effectiveness, recyclability and sustainability. REPOXYBLE assumes an upstream approach more efficient and effective than having to address deficiencies at the end of the product development process. This approach integrates product performance, multifunctionality, sustainability, safety and potential legal concerns, while there is still time to act, on the monomers’ synthesis, the resin formulation and the future composite design. REPOXYBLE is driven by two complementary market applications in the aerospace and automotive sectors.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified189F1BDE-BC7C-437B-AC3C-AA4AC0B677F0UNIVERSITY OF SOUTHAMPTONLEAD_PARTICIPANT410973.0410973.02930848The Multimodal Translation of Intangible Cultural HeritageActiveStudentshipAHRCSchool of Advanced StudyMotivation Intangible Cultural Heritage (ICH) represents the dynamic tapestry of human civilization, encapsulating our collective traditions and cultures. As highlighted by the 2003 UNESCO Convention on the Safeguarding of the ICH, preserving these diverse cultural manifestations is crucial. In the digital era, technological advancements such as transmedia, VR, AR, and 3D modeling allowed diverse forms of information to be digitally transformed and presented in increasingly vivid and comprehensive digital formats (Alivizatou-Baeakou, 2017; Rossau et al., 2019). While these innovations offer unique opportunities to enhance the representation of ICH, they also pose challenges in representing its dynamic, multimodal nature. Furthermore, current digitalisation methods tend to be technocentric and often overlook the cultural contexts and holistic nature of ICH, potentially leading to a loss of its evolving, living character (Carboni & de Luca, 2016). Addressing these challenges necessitates interdisciplinary solutions. There is increasing recognition of the need for a comprehensive digitalisation theory that integrates semiotics with new media technologies (Nantke, 2017), aiming to enrich the digital representation of ICH (Berlanga-Fernández, 2022). As Olteanu & Ciula(2022) argue, "digitalisation-when dealing with conversion across media-are forms of intermedial translation, hence of relevance to translation studies that found its theoretical grounding in semiotics". Building upon this, this research aims to contribute to bridging these gaps by developing a theoretical and practical framework based on multimodal translation theory. This framework, tailored for cross-contextual applications, will bridge traditional understandings with the digital realm. It will focus on digitally preserving and representing the intangible attributes, living nature, and multimodal characteristics of ICH. Aim and Objectives: The overarching research aim of this project is to craft a viable digitalisation pathway for the digital preservation and representation of multimodal ICH content that addresses both challenges and opportunities. The focus is on ensuring long-term development while respecting diverse and multivocal cultural contexts. The objectives are as follows: 1: Apply interdisciplinary multimodal analysis to decode the diverse characteristics of ICH, reflecting its multifaceted nature and significance in socio-cultural contexts. 2: Explore translation strategies for transferring ICH from traditional to digital formats, ensuring the preservation of its intrinsic meaning across different modalities and contexts. 3: Develop a flexible theoretically informed and practically-oriented framework for multimodal translation of ICH, enhancing its digital access and relevance in a rapidly evolving digital world. Contribution: This research introduces multimodal translation from an interdisciplinary viewpoint and aims to provide a theoretically-informed and practically-oriented framework for effectively preserving ICH in today's digital landscape. Academically, it forges a link between systemic functional linguistics and design theory, developing an innovative digital translation system that offers a richer and more culturally attuned representation of ICH. On the application level, the research enhances preservation and dissemination processes, employing advanced digital techniques for efficient data management and broader accessibility. This approach enriches ICH propagation, supports its systematic inheritance, and promotes cultural exchange through a shift towards more dynamic ICH engagement.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedBB/I003916/1How do cells shape and interpret PIP3 signals?ClosedResearch GrantBBSRCSignallingMulti-cellular organisms rely on a large array of different transmitter substances to allow certain cells to control the behavior of others. The more sophisticated the organism the more complex the cell to cell communication. In mammals this language probably involves hundreds of fundamentally different types of transmitter. Clearly such systems need a large collection of specialized receptor molecules that can detect the individual presence of any particular transmitter. Further, these receptors, typically found on the outer surface of the cell's limiting membrane, have to signal their specific stimulation by passing a molecular message into the cells interior, effectively informing the cell that the receptor has been activated. Clearly, if a cell has many different types of receptors on its surface the molecular signal generated inside the cell by each different receptor (often called an intracellular message) must identify and distinguish which specific receptor has been stimulated. Otherwise the cell could not discriminate between the transmitters present on the outside of the cell and could not respond correctly. Hence, mammalian cells have vastly complex intracellular signalling mechanisms continuously informing the cell of what is happening in other parts of the organism or its environment. One such intracellular signalling molecule or 'message' is PIP3. It is a phospholipid molecule found on the inside surface of the cell's limiting membrane. Levels of PIP3 rise rapidly on activation of a large number of receptors. This is surprising given the problems the cell faces in knowing precisely which receptor has been activated when it detects an intracellular signal. This grant application is to understand how it is possible that rises in PIP3 can encode specific messages from so many different receptors. We have performed some experiments that have, in fact, shown that PIP3 in cells is not a single type of molecule. At least four tiny variants of PIP3 can be detected, called molecular species of PIP3. Interestingly, we find that these different molecular species of PIP3 do not respond equivalently to different ways of activating the cells we work with. We and others have also found that the different receptors can make the levels of PIP3 rise for different times and to different maximum levels. We propose that these small differences are very important inside the cell for discriminating whether a certain receptor has been stimulated. This is a 'clever' economy or efficiency on the part of the cell and allows it to use similar mechanisms to perform many different jobs. Although on the surface these might appear trivial details in the business of understanding biology, it has recently been discovered that many different cancers are caused by mutations in genes that regulate PIP3 levels in cells. Mutations that by chance cause the production of PIP3 to be increased without any need for receptor stimulation make cancers much more likely to occur. Mutations that by chance stop the enzymes that normally break down PIP3 from working also make cancer more likely to occur. As a result it is clear that understanding how PIP3 is made and then interpreted by cells is crucial for us to better understand how cancer occurs and how to treat it. Many companies are already trying to design drugs that will reduce PIP3 levels to fight cancer. This work will help us understand how to make better drugs of that type.This proposal is a collaboration between biochemistry groups at BI and mathematical biologists at the EBI to achieve a detailed and quantitative understanding of a major mammalian signal transduction pathway, the PI3K network. Several PI3K isoforms exist in cells that can be selectively engaged by a variety of cell surface receptors to generate the membrane phospholipid PIP3. PIP3 is the initial signal, which is then transduced by 10-50 effector proteins into the regulation of complex cell responses, such as cell growth and movement. Our strategy is to focus on collecting robust, high quality data sets in a panel of isogenic, non-transformed breast cell lines (MCF10a) in which key endogenous components of the pathway can be manipulated and to embed iteration between experiment and modelling to arrive at a more satisfactory explanation of: 1) the key factors which shape the magnitude and spatiotemporal properties of PIP3 signals in response to hormonal stimulation (EGF, insulin, LPA) and oncogenic mutation; 2) The way in which different PIP3 effectors interpret these PIP3 signals and 3) the relative importance of individual PIP3 effectors in delivering regulation of chemokinesis, growth and global transcription. We plan to use homologous gene targetting, siRNA suppression and pharmacological inhibition of pathway components and measure the impact of these perturbations, in several relevant cellular contexts, on i) the levels of PIP3 and other phosphoinositides measured by a novel, quantitative mass spectrometry assay that allows systematic analysis of fatty acid composition; ii) the activity and spatial distribution of several PIP3 effectors (in some cases via knock-in of endogenous GFP-fusion proteins); iii) chemokinesis, markers of growth and global transcription (using next generation sequencing). Models will be built at several levels in the pathway and integrated to allow a deeper understanding of this network and guide more effective therapeutic intervention1) Identify the beneficiaries of this work. See the section 'the beneficiaries'. To restate, ignoring our proximal research community, they would include, within the life-time of the grant; (a) an international and broad group of commercial and academic researchers, (b) the BBSRC, our host Institutions (Babraham and EBI), (c) the post-doc researchers on the grant through the training they receive and (d) our IPA partner Astra Zeneca. In addition, in the longer term, (e) the health care sector, patients and the UK's economic competitiveness. 2) How would they benefit? a) From the technologies and approaches we propose to apply in this application. Most signficantly the lipidomics strategies we have developed to enable sensitive, medium through-put analyses of the different molecular species of PIP3. This advance enables the development of potentially direct read-outs of the effectiveness of PI3K inhibitors in a clinical setting, through the opportunity to take frozen cell or tissue samples and sensitively and quantitatively analyse their PIP3 content. Until now companies have relied on surrogate read-outs of PI3K activity that have a variety of technical and intellectual weaknesses. This approach will also change the phosphoinositide research community, historically there has ben a huge pausity of data in the field through the technical or financial challenges in capturing this type of data. This has severly limited attempts to model this pathway. b) See beneficiaries section. The BBSRC would gain from delivery of their objectives in their recently formulated strategic plan, specifically in the Bioscience for Health priority. As an IPA application, this project has evidence of its commercial relevance as 'basic research underpinning the pharmaceutical sector'. Its use of modelling is in line with the BBSRCs drive to change the culture of modern biology towards being more mathematically based. c) Both the EBI and BI have internationally competitive research environments where the post-docs would learn within a project that has both direct commercial relevance, substantial contact time with a major pharmaceutical company and a multi-disciplinary approach. d) Will benefit from accelerated access to a internationally competitive grouping working in a field in which AZ have direct interest in their inflammation and oncology programmes and from having first option on any IP that might emerge from the project. More specifically they will gain direct leverage from results with the cell lines and inhibitors we have chosen to focus upon; both are used within their own, internal, research programmes. They will also gain early insights into the lipidomics approach we have developed and how they might use it to solve long-standing problems with bio-markers of activity in the PI3K pathway in whole animal or clinical studies. e) These could be longer terms outcomes resulting from improved focus on the most appropriate PI3K targets and hence the best PI3K-selectivity profile of potential drugs in specific therapeutic setting and the development of more relevant and useful bio-markers. As our IPA partners oncology programme is based in the UK (Alderly Edge, Macclesfield) the above should give competitive advantage to UK business. 3) How would we ensure the above potential benefits are realised a) Presentations at international science meetings, publications, good data sharing practice, seminars at companies b) Through the projects funding and execution c) Regular meetings between EBI and BI labs and with AZ researchers (see work plan) d) Through (c) and see Case for support e) The IPA status of this application and the success of past research collaborations (£300K) with AZ are based on our approach to, and conduct within, collaborations with industry. AZ have confidence we will put effort into transferring knowledge and skill and that it will give them competitive advantage in getting good therapeutics into the market-place.2D9083F0-05FA-4726-9EB2-3FCC293CAAF9Biomolecules & biochemistry25999F0B31-F127-410A-A520-963B336BECE7Cell biology25945E0A55-10CB-4E91-BCCB-7CB22CFE2232Tools, technologies & methods1229F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies13EF22E4A7-F12A-4859-8A95-E0179E3570ECBiological membranes12937A9F23-021A-4604-8979-A28E0E04F825Transcriptomics13CA10DA58-174F-4FE6-B61B-8EEBFB8192E2Receptors126D0F40FF-D03E-4429-A764-185BC521A840Catalysis & enzymology132A0F6391-E88A-4396-9D63-25A68EEDA635Communication & signalling13812BD191-6D4F-4F72-852D-0F63AD58ABD8Research approaches122928626Characterising the performance of low loading electrodes for hydrogen technologiesActiveStudentshipEPSRCChemistryThis project is associated with deep understanding of the operation and performance of electrodes for electrochemical devices used in electrolysers, flow batteries, and fuel cells. These devices will allow the efficient capture of renewable electricity and storage/interconversion as hydrogen (see Royal Society report "Large-scale electricity storage"). Deployment of electrochemical hydrogen systems is growing at a tremendous pace, but in order to achieve the well defined KPIs we need: a 10-fold reduction in catalyst requirements; significant improvements in performance; and increased longevity. The purpose of this experimental iCASE is the improved performance of these electrodes whilst reducing the catalyst requirements (and thus cost), coupled to improved understanding and ability to model the performance of these systems. Such improvements can only be achieved through a deeper understanding of performance of the electrochemical interface at which reactants, electrons and ions must be efficiently transported to the catalytic interface. These systems are crucial for the UK and world to reach their net-zero aspirations by 2050. The topic cuts across a number of themes in the UKRI including the Energy and decarbonisation theme (Solutions to reach net zero), the Manufacturing the future theme and the Physical Sciences theme. The project is extremely well aligned with the UK's 2022 NMS strategy for which 'the measurement infrastructure needed to support the hydrogen economy as it develops' is a government priority6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified10181283MUSHFORM: Transforming Spent Mushroom Substrate into High-Performance, Chemical-Free Pulp Moulded PackagingClosedCollaborative R&DInnovate UKImagine if the containers holding your supermarket mushrooms were made from the waste generated growing those same mushrooms. That circular vision is exactly what MUSHFORM aims to prove. **The Double Problem We're Solving** UK mushroom farms produce over 100,000 tonnes of delicious mushrooms annually---but create over 500,000 cubic metres of "spent substrate" waste, costing growers £3-15M annually to manage. Meanwhile, food packaging manufacturers import wood pulp, blast it with harsh chemicals (caustic soda, chlorine bleach), consume massive energy (3,500-4,500 kWh per tonne), then add plastic coatings to create containers that never truly biodegrade. Two industries. Two problems. One circular UK solution. **Nature's Hidden Gift** Here's the breakthrough: mushrooms are nature's master decomposers. As they grow, their fungi release powerful enzymes that break down tough plant materials---essentially doing 70% of the pulping work that paper mills achieve with toxic chemicals. After harvest, the spent substrate has already been biologically "pre-processed." Think of mushrooms as unpaid factory workers, preparing packaging material while producing food. **The Technology** Led by Yr Ardd Fadarch Eryri Cyf. t/a Madarch Cymru, working with Bangor University's pilot facility (managed by professional project specialists), we'll test whether three types of spent mushroom substrate can be transformed into sturdy food packaging using only mechanical processing---no chemicals, no bleaching, no plastic coatings. Just steam, pressure, and precision engineering. **The Products** Picture supermarket eggs in trays made from mushroom waste. Takeaway containers that started life supporting shiitake cultivation. Protective packaging that could literally return to mushroom farms as compost. Products---egg cartons, food trays, corner protectors---are home-compostable in 12 weeks, cost less than imports, eliminate chemicals, and convert growers' disposal costs into revenue, closing the perfect loop: waste from food production becomes food packaging. **Why This Matters---Supporting UK Communities** Mushroom growers transform £3-15M annual disposal costs into revenue. Packaging manufacturers access over 500,000m³ of pre-processed, domestic feedstock. By Year 5:35 rural jobs created across UK mushroom-producing regions, £1.2M tax revenue generated, supporting economic development in agricultural communities. Consumers get packaging with genuine environmental credentials---not "industrially compostable" but actually biodegradable in your garden or back in mushroom production. This is the circular economy in its purest form: one food sector's waste becomes another's feedstock, processed domestically, used domestically, composted domestically, then returned to UK farms. No imports. No chemicals. No waste. Welcome to packaging that completes the cycle it began in from soil, through mushrooms, carrying food, then back to soil---or back to mushrooms.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedEBFD9F58-E3A8-4CF6-92C4-9373A106626EYR ARDD FADARCH ERYRI CYF.LEAD_PARTICIPANT25000.025000.010037439Eye in the SkyClosedCollaborative R&DInnovate UKAbstracts 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.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified3D4B99F1-29FB-4CE3-8D6A-444518FD03EANATIONAL GAS TRANSMISSION PLCPARTICIPANT0.00.0CD432890-34DA-454F-90BE-D3033081FEEADNV SERVICES UK LIMITEDPARTICIPANT0.00.0614B0FA0-9759-4C48-A17A-E167CDB4424BNATIONAL GRID ELECTRICITY TRANSMISSION (NGET)LEAD_PARTICIPANT0.00.0F1B6C800-F277-46F6-8183-9B07CBF77E6ESPOTTITT LTDPARTICIPANT0.00.010008315VANTAGE - An intelligent payload that enables UAVs to autonomously land on maritime vessels, ultimately addressing Urban Air Mobility requirements.ClosedBEIS-Funded ProgrammesATIAbstracts 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.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedF29B0E65-061D-4B63-95EC-A2D2BBC2DEAFEMBEDDED LOGIC LIMITEDLEAD_PARTICIPANT196091.0137264.0B4C1B286-0775-4915-87BA-39063C062D21BIT PARALLEL LIMITEDPARTICIPANT103909.072736.01677978Development of molecular imprinting with liquid chromatographt-massClosedStudentshipBBSRCCancer Studies and Molecular MedicineDevelopment of molecular imprinting with liquid chromatography-mass spectrometry HD-SRM for the sensitive and selective detection of proteins6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified