710397Wittos - Mobile Internet Analytics & Predictive Content Over WiFiClosedGRD Proof of ConceptInnovate UKThe increasing availability and uptake of smart mobile devices offering broadband connectivity has raised demand for a smarter in-store experience, specifically a means for bricks and mortar retailers to connect to and engage with their customers. Whilst analytics of traditional Internet user behaviour has matured, and a myriad of solutions offering insight and engagement have evolved, no comparable solutions exist to offer retailers insight into a customer's online behaviour whilst within their premises. Wittos has developed a breakthrough new solution that offers real-time actionable intelligence and awareness of the customer's in-store intentions. This technology forms the core of the Wittos platform which builds upon a traditional Wireless hotspot offering Internet connectivity. Wittos combines data gathered from the user's online activity, their physical location and path through a venue and uses this to match their actions to a behavioural profile (companion or shopper). This profile can then be matched with products of interest (their online focus) and acted upon to serve the most relevant content to user or improving their instore experience by providing real-time intelligence to staff on the floor. This reactive intelligence offers the retailer a means to increase the customer’s dwell time and increase the chance that an in-store customer transacts. This technology will offer traditional retailers a competitive advantage as relevant alternatives to their purely electronic competitors, a greatly improved in-store customer experience and the ability to match demand and supply in real-time.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified6380BFC8-096F-4D6F-8151-869D08B3288FWITTOS LTDLEAD_PARTICIPANT165589.090461.02444772Post-Translational Modifications Orchestrate Organ SymmetryClosedStudentshipBBSRCPostgraduate Research ServiceA major challenge during morphogenesis includes the establishment of symmetry types, such as radial and bilateral symmetry: a developmental commitment which greatly impacts on organ function. In humans, defects in organ-symmetry establishment leads to malformation and diseases, but despite its importance, our knowledge about symmetry foundation in multicellular organisms is very limited. Less intuitively, organ symmetry establishment is fundamental for plant survival too. Therefore, the aim of this project is to shed light on a new mechanism regulating radial and bilateral symmetry establishment during plant organogenesis, using A.thaliana as a model; investigating how a specific post-translational modifications underpins direct protein interactions between key regulators of plant organ symmetry, which in turn switches on and off gene expression, precisely and quickly, during organ development.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified2434402Random metrics on the CLE carpetClosedStudentshipEPSRCPure Maths and Mathematical StatisticsConformal loop ensembles (CLE) are random collections of loops defined in simply connected domains. They exhibit a fractal structure and arise as conjectured and proved scaling limits of a number of lattice models from Statistical Physics. Since their introduction, connections between CLE, Schramm-Loewner evolution (SLE) curves, and the Gaussian Free Field (GFF) have been shown and categorized. In this project we consider natural random metrics defined on the set of points not surrounded by CLE loops (the CLE carpet) and investigate their properties. A first goal is to build on the relationship between CLE, SLE, and the GFF to show that geodesics in a natural CLE metric are singular with respect to SLE. This disproves a conjecture from 2014 that was based on empirical results.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedAH/V01241X/1ENGLISH HERITAGE TRUST CONSERVATION AND HERITAGE SCIENCE FACILITY - RANGER'S HOUSE, GREENWICH, LONDONClosedResearch GrantInfrastructure FundThe English Heritage Trust (EHT) cares for the National Heritage Collection of 400 historic sites and 3/4 million associated artefacts. The Facility The heritage science and conservation facility at Ranger's House acts as a central hub for core research and conservation activities carried out by EHT. The facility itself comprises five rooms in the apartment adjacent to the publicly accessible house (home to the Wernher Collection), the fine art conservation studio, and an outbuilding used as a store. The facility has grown organically and has reached a point where the scale of work outstrips the capacity of the facility - both due to space and the quality of equipment within. The Beneficiaries - People and Collections The English Heritage Conservation Science team has been leading the way in research on the environmental response of objects in historic environments. This work has been critical in allowing for the safe display and storage of the collection in historic buildings. Its novelty lies in the combination of close object/ building examination and analysis, with an epidemiological approach. We have been able to develop this novel approach because we look after similar objects that are exposed to a range of very different environments. The practical methods we have devised as a result of our research have enabled us to reduce the carbon footprint of conservation activities by 40%. The sector's interest in this work is demonstrated by an impressive 70 publications in competitive forums, the oversubscription to a series of 8 international courses covering management of showcases and an invitation to the 2018 Gordon conference on Scientific Methods in Cultural Heritage Research. We have also supported six PhDs - looking at response of lined canvas paintings, archaeological bone, archaeological glass and outdoor artillery - through the CPD scheme, SEAHA doctoral training scheme, AHRC Collaborative Doctoral Program and the Science and Heritage Programme. This research would not be possible without the Ranger's facility and its equipment, but it has been severely restrained by lack of space and outdated equipment - with constant failures or issues with software compatibility. The conservation studio at Ranger's House, often guided by scientific advice from the conservation science team, carries out practical treatments and technical analysis of the English Heritage collection of over 1500 easel paintings, many of international significance, and their associated frames. Technical examination advances our understanding of an artist's materials and methodology. Over the last five years our work has resulted in the reattribution of several paintings, notably to Botticelli and Titian, and much associated publicity for English Heritage has followed. Art historical findings relating to paintings by Rembrandt, Titian, Weenix and Beuckelaer have been presented at several national and international conferences and published in postprints and journals. To allow this treatment and research to continue, we need to update equipment in line with technological advances and remedy issues with the studio space, previously adapted from an old coach house The Project The amount of research needed, both within the EHT strategy and to support the sector, is not possible within the confines of the existing facility, nor with equipment more than 10 years old and suffering constant failures (and not supported by the manufacturers due to its age). We will redevelop the interiors of the facility and upgrade the store into a workshop in order to house equipment, and provide space for sample preparation and wood working for fine art conservation. We will also replace the most outdated pieces of equipment, to significantly improve the efficiency for research undertaken in the facility.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedNE/P000061/1Characterising hydrothermal alteration across the Atlantis Massif: IODP Expedition 357ClosedResearch GrantNERCSchool of Geog Earth and Environ SciencesThe oceans covers approximately two thirds of the Earth's surface yet the oldest ocean floor is less than 200 million years old because it is continuously created and destroyed through the plate tectonic cycle. The ocean floor is made of volcanic rocks that form at mid ocean ridges, a global chain of under-water volcanoes that stretch for ~60,000km around the oceans, where two tectonic plates are moving away from each other. The rate at which the two tectonic plates move away from each other varies across the oceans. Currently 50% of the global mid ocean ridge system is spreading at slow spreading rates (<40 mm/yr, e.g Mid Atlantic Ridge). From dredging and scientific drilling of the ocean crust and studying ophiolites, pieces of ocean crust that have been emplaced onto the continents, the overall structure of the ocean crust has determined. 'Typical' ocean crust has a layered stratigraphy with erupted lavas overlying intrusive feeder channels and frozen magma chambers (gabbros). However along slow spreading ridges this typical stratigraphy is not always present, and ~ 50% is formed by tectonic extension along detachment faults that bring gabbros and mantle rocks to the seafloor. Once new ocean crust is formed cold seawater penetrates downwards into the crust along fractures, becomes heated and reacts with the volcanic rocks until the hot hydrothermal fluids becomes buoyant and exit the crust at the seafloor . These reactions modify the chemistry of both the rocks by the formation of new hydrothermal minerals and the hydrothermal fluids, and are therefore an important process to quantify in order to understand global chemical exchange. The new minerals that form are strongly dependent on the initial rock and the temperature of the reacting hydrothermal fluids. At slow spreading ridges, the exposure of gabbroic and mantle rocks at the seafloor results in different chemical reactions, and mantle rocks in particular undergo extensive alteration to serpentinites. Serpentinisation reactions are accompanied by the formation of calcium carbonate minerals in fractures. The formation of calcium carbonate by fluid/rock reactions is currently being investigated as a potential long-term store of carbon dioxide. Understanding hydrothermal circulation in these environments is critical for understanding this process and ultimately exploiting it for the industrial storage of carbon dioxide. The Atlantis Massif is located on the Mid Atlantic Ridge and is an example of where tectonic extension has exposed gabbroic and mantle rocks at the seafloor. A hydrothermal vent system called the Lost City Hydrothermal Field is present on the southern end of the massif and is driven by serpentinisation reactions. Low temperature (<100degC), high pH hydrothermal fluids vent diffusively at Lost City through carbonate-brucite structures. It is one of only five hydrothermal vents that are known to be hosted on mantle rocks. In this study, new samples recovered by scientific ocean drilling of the Atlantis Massif during IODP Expedition 357 will be used to investigate the role of hydrothermal circulation in the formation of ocean crust along these long-lived detachment faults. For the first time an age transect of samples across the massif has been recovered allowing insight into how the detachment changes and evolves as it progressively ages. By studying the new hydrothermal minerals that have formed during fluid/rock reaction, and documenting their distribution within the different rock types, the pathways for the hydrothermal fluids can be deciphered. This information will be combined with geochemical analyses of the rocks and hydrothermal minerals to quantify the chemical changes that have occurred during hydrothermal circulation across the Atlantis Massif. This combined approach will allow the contribution of hydrothermal circulation along detachment faults to the broader hydrothermal budget of global geochemical cycles to be determined.This project will make significant scientific advances towards our understanding of the role of hydrothermal circulation during the formation and evolution of the ocean crust. It will expand upon our current knowledge of this key Earth process through the variable slow spreading rate crust that represents much of the modern mid ocean ridge network. This project will primarily benefit the extensive ocean crust community, both those working on modern ocean crust and ophiolites, as outlined in the Academic Beneficiaries section. Benefits to: IODP The proposed research will contribute to addressing two of the proposed challenges in the 2013-2023 IODP Science Plan; challenge 9 'how are seafloor spreading and mantle melting linked to ocean crustal architecture' and challenge 10 'what are the mechanisms, magnitude, and history of chemical exchanges between the oceanic crust and seawater?'. This research will contribute to these by characterising and quantifying hydrothermal circulation through the detachment surface of the Atlantis Massif and its contribution to global geochemical cycles. Publication of this research in internationally recognised peer-reviewed journals will highlight the on-going importance of IODP as a world leader in scientific collaboration and high impact science. Benefits to: Public This research will contribute to topical global questions about the response of the Earth system to perturbations (global geochemical cycles) and the limits of life. Through the integration of this study with companion studies addressing the mechanisms of serpentinisation because of the intimate link between the two studies, this research will contribute to the topical debate about the long term storage options for atmospheric carbon dioxide. Involvement with University open days and public engagement activities (e.g. Girls into Geoscience) and the publication of the results in journals accessible to the public will ensure this research is exposed to the public. Benefits to: RA The research assistant will benefit from training and experience in laboratory procedures in addition to being involved with active research. It will provide an opportunity to extend their skill set and develop their future career prospects. Benefits to: Industry The long term storage of carbon in solid mineral form is one of the options available for reducing atmospheric carbon dioxide and is currently an area of research of high interest in both academic (e.g. IODP Expedition 357, ICDP Oman Drilling Project) and industrial (e.g CarbFIX) contexts. A necessary step towards the potential industrialisation of this process is understanding the natural system in a range of environments. This research is intimately linked to serpentinisation across the Atlantis Massif and will therefore help inform our understanding of the formation of calcium carbonate minerals in lower crustal and mantle rocks. This research will add to the growing body of research in this field and in the long term will be of use to carbon capture and storage industries. How does the proposed research generate impact? This research will inform our understanding of the variation in processes that form the ocean crust. The recent recognition of the extent of the detachment mode of seafloor spreading represents a major step in our understanding of how the Earth surface forms. The results of this study will provide crucial evidence for the interaction of hydrothermal fluids and tectonic processes and quantify for the first time the contribution of focused hydrothermal fluids on global hydrothermal budgets. The intimate link between hydrothermal circulation in the gabbroic and mantle rocks will inform our understanding of the natural storage of carbon in ocean crust, a crucial step in knowledge necessary for the potential industrialisation of this process.346611FD-47F5-46D6-9813-D4707F62253BGeosciences100F52704F6-1035-4307-9FA9-45BC878F1F1ATectonic Processes107F1C4565-EFD3-4BE7-8A4A-B5F39FFD36F3Volcanic Processes302334C846-D357-4EF1-B929-0EC4EC1854CBHydrogeology40A646062E-6497-4533-8274-47644A7B369CEarth Resources20EP/H023666/1Ferroelectrics for Nanoelectronics (FERN)ClosedResearch GrantEPSRCElectrical, Electronic and Computer EngThe evolution of silicon technology since the 1960's has focussed on doubling performance and functionality every 18-24 months through miniaturization. Critical dimensions measured in tens of nanometres are now common place and billions of components connected by miles of wiring can be packed onto a wafer no larger than a thumb nail. Today the focus is shifting away from more scaling (called more Moore after the founder of Intel, Gordon Moore) towards increasing functionality through the introduction of mixed technologies on silicon (called more than Moore). This project investigates the incorporation of ultra thin ferroelectric materials into silicon nanoelectronics and two of its many applications.Capacitance is the rate of change of charge with voltage. It is the defining property of capacitors which are necessary in many electronic systems but are relatively large. Ferroelectrics can shrink capacitors by three orders of magnitude, because their electric permittivity is so high. More than that, their capacitance can be made to vary depending on the applied voltage so very small and tunable capacitors can be made, which can find applications in hand held electronics products in order to reduce power consumption. If they could be integrated onto a silicon microchip there would be further space savings. Thin layers are expected to produce even higher capacitance. However there is evidence that capacitance starts to reduce below 50 nm as dead layers are said to form near the interface with electrodes, but this may be an interface effect which can be lessened through engineering. Recently there has been experimental evidence that effective negative capacitance can be seen in ultra-thin ferroelectric films. If such material can be incorporated into a transistor then it would be able to reduce the voltage needed to switch a transistor between its on and off states (the sub-threshold slope). This would transform silicon technology, allowing a new generation of more powerful single core processors. Modern computers have dual or multi-core processors. A single core processor would generate too much heat but is still desirable for many applications. Capacitance places a lower limit on the sub-threshold slope. The consequence is that transistors need a larger applied voltage to be on and/or will leak current and so can never be fully switch off. This leads to increased power loss and heating as more transistors are crammed onto the same area of silicon, which limits component density. Integrating a ferroelectric film with negative capacitance into the gate of a transistor would reduce the overall capacitance and thus the sub-threshold swing. The need to understand and produce high quality ferroelectric ultra-thin films is imperative for each of these applications. Atomic Layer Deposition (ALD) at Newcastle and Pulsed Laser Deposition (PLD) at Imperial College will be used to deposit thin films of the ferroelectric materials barium titanate (BTO) and barium strontium titanate (BST). Both allow deposition thicknesses with atomic level precision. Extensive characterisation is needed to assess quality of these ferroelectric films. First principles computer simulation will be used to gain a better understanding of the films and to direct experiments. The deposition and thermal parameter space will be mapped to identify best ferroelectric properties for given constraints laid down by the silicon fabrication. Transistors will be made incorporating the best ferroelectric films to confirm the reduction in sub-threshold slope. Ferroelectric capacitors integrated onto silicon will be demonstrated, quantifying the capacitance increase per unit area and examining the fabrication constraints needed to maintain high transistor performance. This will also help identify integration issues, which also include equipment contamination and the development of ferroelectric etches.The RAs and PG student trained will have the opportunity to develop excellent analytical, research and communications skills. Such people have previously gone on to work as permanent academic staff, in industry, in finance and in government research labs. The project will offer other RA's and PG students an opportunity to benefit from working on closely related topics in the area of thin film ferroelectrics and it is anticipated that this will boost the activity to benefit all. UK companies spanning the supply chain for high performance integrated circuits will gain competitive advantage. The primary benefits will be proof of concept for new types of semiconductor devices using ferroelectric thin films and the reduction of risk for development and manufacture of products using these devices. Materials companies benefit from expertise within this consortium and IP generated. Knowledge gained will accelerate their progress in producing high quality films for many applications. They can license the recipes for deposition of ferroelectric thin films adding value to their deposition system. They will benefit from the collaboration, especially characterisation and device data which will reassure customers. Mixing silicon with ferroelectrics for high permittivity voltage controlled capacitors will have the benefit of allowing single chip solutions where previously several components may be necessary. Using ferroelectric films to reduce transistor sub-threshold slope is high risk but has the potential for enormous benefits. The exponential increase in microchip leakage power and heating, as critical dimensions reduce and transistor count increases has halted single core processor evolution in favour of multiple core processors in order to have effective thermal management. A reduction in power consumption by integrated circuits must be of global benefit to the environment, since almost every appliance uses some silicon technology. Beneficiaries will include not only the semiconductor manufacturers, circuit designers and product manufacturers, but all of us who use their products. Ferroelectrics are also piezoelectric and pyroelectric and so a range of intelligent sensor/actuator systems might be envisaged. While the UK does not at present have state of the art silicon manufacturing, it is likely that in future UK based companies will partner with overseas semiconductor foundries for the supply of part-processed wafers (the transistors and some interconnect metallisation) which can be completed integrating a variety of mixed technologies (such as thin film ferroelectrics for tunable capacitors) to create IP intensive products of high added value. This may be particularly appropriate for partnering within the EU where it can make economic sense to share expensive semiconductor foundries. Publication of research in high quality journals and at leading international conferences is crucial and will continue. The industrial steering group will be a means of two-way communication and engagement between this academic project and the commercial sector. National electronics networks like Si Futures, UKDF and EU networks like Sinano will be accessed. Press releases to the trade press will also be used to announce the project and to publicise breaking news as it develops. The research will feature on web pages of the two universities. The quarterly management meetings will have a standing item on potential impact of research. Promising strands of research will be pursued and our steering group members will be approached for additional guidance. Patents will be sought where possible prior to publication of the research. Both PIs have previous experience of knowledge transfer to industry. Both universities have excellent media staff to help with communication.1908FDF5-1C61-4F33-B47F-3E91675C88AAInfo. & commun. Technol.50177C04BB-BFD4-4D65-BA9D-15A50728B8CAMaterials sciences2550CC55CC-BE0D-4167-BD99-285D6BCC369BMaterials processing2550CC55CC-BE0D-4167-BD99-285D6BCC369BMaterials processing252B23EFD7-00EA-4FCA-8685-A8B4B94BF976Electronic Devices & Subsys.50BEA752D6-11B4-4E5F-937C-2DD41104E229Materials Characterisation25750553Safe 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/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.F673FD2B-013B-47E5-9E62-03BAB1E7348EEnvironmental engineering104CCA4C04-0C28-41BE-8869-FA6391A7F005Microbial sciences2029F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies70AF3F5E7C-7FB6-4588-9174-6018BA2A231BEnvironmental Microbiology20937A9F23-021A-4604-8979-A28E0E04F825Transcriptomics107E61B40B-93E5-4D69-8C89-426ED7E0D2B4Metabolomics / Metabonomics20513702B4-7C48-41F2-A1A0-8B4E8BEDCABCAssess/Remediate Contamination10C6A85141-ED79-4266-86E5-F6D25217C97FEnvironmental Genomics402430216Real-time prediction of cellular states in 3D lattice light sheet microscopyClosedStudentshipMRCProgramme 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-C47AE53E333EUnclassified10159543ERDERA - EUROPEAN RARE DISEASES RESEARCH ALLIANCEActiveEU-FundedHorizon Europe GuaranteeThe European Rare Diseases Research Alliance (ERDERA) aims to improve the health and well-being of the 30 million people living with a rare disease in Europe, by making Europe a world leader in Rare Disease (RD) research and innovation, to support concrete health benefits to rare disease patients, through better prevention, diagnosis and treatment. This Partnership will deliver a RD ecosystem that builds on the successes of previous programmes by supporting robust patient need-led research, developing new diagnostic methods and pathways, spearheading the digital transformational change connecting the dots between care, patient data and research, while ensuring strong alignment of strategies in RD research across countries and regions. Structuring goal-oriented public-private collaborations targeted at interventions all along the R&D value chain will ensure that the journey from knowledge to patient impact is expedited, thereby optimising EU innovation potential in RD. To support its ambition and missions ERDERA has been designed as a comprehensive and integrated ecosystem of which structure can be compared to an institute encompassing three main parts: (i) funding, (ii) internal (in house) Clinical Research Network that implements research activities targeting clinical trial readiness of RDs and accelerating diagnosis and translation of research discovery into improved patient care, and (iii) related supporting services (Data, Expertise, Education and Training) as well as an acceleration hub that serve external and internal RD community, all supported by all-embracing coordination and strategy and foundational (inter)national alignment.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified13C979ED-CCCE-4C21-9953-307B6EC53D42NEWCASTLE UNIVERSITYLEAD_PARTICIPANT265671.0265671.02594586Using Artificial Intelligence to Understand Zeolite CatalystsClosedStudentshipEPSRCMaterialsElectron microscopy provides a unique tool for studying the local structure of materials at the atomic scale. However, a major challenge lies in correlating bulk measurements of properties with highly selective structural data. One approach is to take advantage of fast electron detectors to acquire large data sets of millions of images and to develop automated analysis tools based on deep learning to analyse these. The overall aim of this project is to study defect structures in zeolites involved in heterogeneous catalysis. This project will use recent developments in fast direct electron detectors for transmission electron microscopy for low dose imaging and neural networks trained for pattern recognition of specific defect structures. The potential impact of these studies is a better understanding of catalytic processes of interest to the industrial sponsor and an improved understanding of the relationships between catalytic performance and local structure. Initially the project will use new detectors operating at kHz frame rates to record large datasets containing many TEM images of defect structures. In parallel the project will develop the use of machine learning based on convolution neural networks to build image analysis tools suitable for analysing large data sets containing millions of images. A convolutional neural network will be trained using simulated data of known defect structures for various electron dose budgets and other imaging conditions. This will then be used to analyse the experimental data to gain meaningful statistics on defect types. The research proposed relies heavily on unique instrumentation available at the electron Physical Sciences Imaging Centre. Specifically, a new high speed direct electron detector operating at a frame rate in excess of 2KHz in 12 bit counting mode will be used to acquire low dose data. Within all of the above aims and objectives it will be necessary to ensure that the methods developed are robust to low dose data acquisition as zeolites are known to be radiation sensitive and to ensure that electron beam induced effects are minimised. Initially pure zeolites will be studied but the project will also be extended to study metal loaded zeolites and comparisons between defects in these systems and the pure materials will provide insights into the mechanisms and structural consequences of metal loading. Finally catalytic data will be measured at the industrial sponsors laboratories to attempt to correlate catalytic performance with the nature and densities of defects present across a range of loaded and unloaded samples The project falls within the EPSRC energy, Artificial Intelligence and Robotics and physical sciences research areas The project is funded by Johnson Matthey plc through the iCase initiative.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedMR/Y016629/1Predicting Biological Carbon in the Ocean Globally (PRECOG)ActiveFellowshipUKRI FLFEarth, Ocean and Ecological SciencesEmissions of carbon dioxide (CO2) from our society are rapidly warming our climate to currently 1.1 degrees C warmer than in preindustrial times. Global governments have pledged to reduce emissions to stabilise our warming climate at 1.5 degrees requiring us to reduce emissions of CO2 to a point where they no longer accumulate in the atmosphere: Net Zero. A crucial consideration in this effort are natural reservoirs of carbon on the Earth's surface such as permafrost and soils that store large amounts of carbon away from the atmosphere, but which are vulnerable to environmental change. The destabilisation of these reservoirs over time, releasing more CO2 into the atmosphere, presents a challenge to stabilising climate upon reaching Net Zero. Therefore, predicting how these natural carbon reservoirs will change in the future is a crucially important task. The Biological Carbon Pump is one of these natural reservoirs of carbon in our Earth System. It stores carbon in the ocean by plankton (microscopic plants) taking up CO2 as they grow in the surface ocean. The sinking remains of these plankton carry the carbon into the deep ocean locking it away for hundreds to thousands of years. This carbon pool is equivalent in size to the anthropogenically-driven increase in atmospheric CO2 over the 20th century. The Biological Carbon Pump is widely expected to be sensitive to environmental change and could therefore release CO2 in the future. However, we have limited knowledge of what those changes might be and why because we don't have the necessary outputs from the state-of-the-art future projections by Earth System Models that underpin the Intergovernmental Panel on Climate Change (IPCC) reports that inform social, economic and political decisions about Climate Change. PREdicting biological Carbon in the Ocean Globally (PRECOG) will build a team of experts at the University of Liverpool to comprehensively explore the future of the Biological Carbon Pump using state-of-the-art Earth System Model projections. PRECOG will strategically align with an international network of researchers and industry partners to build a new knowledge framework that will inform future IPCC reports and mitigation strategies. PRECOG will: 1) Derive new standard quantitative measures of the Biological Carbon Pump in a future changing ocean. 2) Quantify how and why the Biological Carbon Pump changes in state-of-the-art future projections that underpin the IPCC reports. 3) Determine the long-term impact of the Biological Carbon Pump beyond the year 2100 using new Earth System Model simulations. 4) Predict which future projections of the Biological Carbon Pump are most likely and how this might impact schemes to artificially enhance carbon storage by combining future projections with new compilations of observations. PRECOG has a strong focus on connecting scientific outcomes to societally relevant outcomes. The research team will maintain a strong and active link with IPCC activities through its international network with the aim of raising the profile of Biological Carbon Pump research. PRECOG will also work with industry partners interested in techniques that will enhance the carbon storage of the Biological Carbon Pump to help mitigate rising CO2 such as kelp farming and seeding the ocean with iron. PRECOG will provide the state-of-the-art estimates for the best locations to undertake these activities and disseminate these findings through its industrial partners. In summary, the Biological Carbon Pump is a vulnerable natural carbon pool in the ocean that can influence atmospheric CO2 in response to environmental change. The future of this carbon pool is however poorly known. This Future Leaders Fellowship, PRECOG, will establish a team of experts to explore the Biological Carbon Pump in state-of-the-art IPCC projections to find out what the likely future changes are and translate this is into a societally relevant agenda.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedBB/I003916/1How do cells shape and interpret PIP3 signals?ClosedResearch GrantBBSRCMulti-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.945E0A55-10CB-4E91-BCCB-7CB22CFE2232Tools, technologies & methods122D9083F0-05FA-4726-9EB2-3FCC293CAAF9Biomolecules & biochemistry25999F0B31-F127-410A-A520-963B336BECE7Cell biology2529F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies13EF22E4A7-F12A-4859-8A95-E0179E3570ECBiological membranes12937A9F23-021A-4604-8979-A28E0E04F825Transcriptomics13CA10DA58-174F-4FE6-B61B-8EEBFB8192E2Receptors122A0F6391-E88A-4396-9D63-25A68EEDA635Communication & signalling13812BD191-6D4F-4F72-852D-0F63AD58ABD8Research approaches126D0F40FF-D03E-4429-A764-185BC521A840Catalysis & enzymology132928626Characterising 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-C47AE53E333EUnclassified105242Replacing non-recyclable black plastic: Development of the first fully compostable, oven-proof, long shelf-life tray for ‘ready-meal’ and modified atmosphere packagingClosedFeasibility StudiesInnovate UK"**AMBITION** Our aim is to reduce and replace the use of black non-recyclable plastic for modified atmosphere packaging for ready-meals and ambient food items with development of a natural, fully compostable alternative packaging technology. Over 1.3 billion black plastic trays are used in the UK each year (~10 billion globally- [Greenpeace][0]) however low recycling rates (45% plastic recycling rate UK; 9% globally-Defra;2018) and the inability of IR recycling plant sensors to the colour black mean that 99% of black plastic food trays end up in landfill, or even worse in the ocean. Although work is being done to increase the recyclability of black plastic, high recycling costs coupled with low recycling rates mean that what is needed is move away from plastic all together, towards natural, sustainable alternative materials. **FOCUS** Working with a strong consortia of sustainable packaging and manufacturing experts, the project focuses on design and development of a fully compostable (6 weeks), heat-resistant (up to 240oc), microwavable and freezable food tray with unique biopolymer coating using seaweed algae and corn starch to provide up to 21 days atmospheric protection for ready-meal and ambient raw meat/fish market. Made solely out our natural materials, the tray will be designed and tested using a number of FSA (UK), EU and FDA (US) approved protocols to ensure it meets the required oxygen transfer, water vapour transfer, temperature, disease and thickness requirements of each food safety agency and target food producer customers **SIGNIFICANCE** Despite an increased focus on reducing plastic waste and significant consumer and supplier demand, the technical challenges associated with replacing black plastic with natural alternatives for modified atmosphere food packaging have not been solved. Our strong biopolymer barrier technology therefore represents a step-change in the industry, still dominated by black plastic.Furthermore as a fully-compostable solution, it is both significantly cheaper and easier to dispose of than recycled plastic alternatives. In line with UK GOVs 'Plastic Pact' 2025 commitment, all our materials are naturally-sourced and therefore have the potential to reduce the UK's reliance on plastics in this area significantly -- opening up a £32m turnover opportunity for us by Y5\. We have already been in advanced discussions with Iceland and Kerry Foods regarding early adoption of the technology when developed and see this as having global potential -- environmental friendly and significantly cheaper than developing new plastic recycling infrastructure. [0]: https://www.huffingtonpost.co.uk/entry/why-cant-black-plastic-be-recycled_uk_5b18f4e1e4b0734a993b00d0?utm_hp_ref=uk-lifestyle"6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified7DB3A6D4-2C87-453C-AA23-11C5D7ADD7CCBIOPAXIUM TECHNOLOGIES LIMITEDLEAD_PARTICIPANT496770.0347739.010181283MUSHFORM: 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-C47AE53E333EUnclassifiedCD432890-34DA-454F-90BE-D3033081FEEADNV SERVICES UK LIMITEDPARTICIPANT0.00.0F1B6C800-F277-46F6-8183-9B07CBF77E6ESPOTTITT LTDPARTICIPANT0.00.0614B0FA0-9759-4C48-A17A-E167CDB4424BNATIONAL GRID ELECTRICITY TRANSMISSION (NGET)LEAD_PARTICIPANT0.00.03D4B99F1-29FB-4CE3-8D6A-444518FD03EANATIONAL GAS TRANSMISSION PLCPARTICIPANT0.00.010008315VANTAGE - An intelligent payload that enables UAVs to autonomously land on maritime vessels, ultimately addressing Urban Air Mobility requirements.ClosedBEIS-Funded ProgrammesATITo develop an intelligent payload that visually identifies landing pads, at day and night, and enables UAVs to perform autonomous landings on fixed or moving platforms, focusing initially on maritime applications. This technology will become part of an integrated suite of autonomous functions ultimately addressing the requirements of Urban Air Mobility,6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedB4C1B286-0775-4915-87BA-39063C062D21BIT PARALLEL LIMITEDPARTICIPANT103909.072736.0F29B0E65-061D-4B63-95EC-A2D2BBC2DEAFEMBEDDED LOGIC LIMITEDLEAD_PARTICIPANT196091.0137264.01677978Development 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-C47AE53E333EUnclassifiedBB/G001103/1Regulation of the immune response: the role of integrin alphavbeta8 and TGF-beta in immune homeostasis and response to pathogens.ClosedResearch GrantBBSRCLife SciencesThe immune system functions to detect and destroy harmful pathogens that enter the body. Upon infection, the immune system is rapidly activated, to ensure the threat is dealt with as quickly as possible. However, in healthy individuals it is vital that the immune system is kept in a resting state to prevent tissues of the body from being attacked; a process that results in debilitating autoimmune disease. A vital area of research is concerned with understanding the pathways and molecules that control the balance between a resting and active immune system. We have recently identified a vital pathway which prevents the immune system from attacking tissues of the body. When a protein molecule called integrin alphavbeta8 is not present on the dendritic cells of the immune system, severe autoimmune disease occurs. The work proposed here aims to study this pathway in more detail, looking at which specific types of cell in the immune system are important, and to determine what happens to this pathway during active immune responses to infection. Such work will provide important insights into how animals and humans successfully deal with infection, and how the immune system is tightly regulated to prevent autoimmune disease.The immune system has evolved to protect the body from infection by quickly detecting and destroying harmful pathogens. However, in normal circumstances, it is vital that the immune system is kept in a resting state, to prevent harmful immune responses directed against self-tissues, leading to autoimmune disease. An important molecule in the regulation of immunity is the cytokine transforming growth factor-beta (TGF-beta). TGF-beta is an important anti-inflammatory cytokine, as shown by the TGF-beta1 knockout mouse, which dies from multi-organ autoimmune disease due to unregulated immune responses. TGF-beta is synthesized and secreted from cells as part of a latent protein complex, and needs to be activated to exert effects on TGF-beta receptor-expressing cells. Therefore, increasing our knowledge of how TGF-beta is activated in vivo will be vital in understanding how TGF-beta regulates the immune system. Our recent studies have uncovered a novel role for the integrin alphavbeta8 in activating TGF-beta in the adaptive immune system. Mice lacking integrin alphavbeta8 on antigen-presenting dendritic cells develop severe autoimmune disease, characterised by unregulated T-cell activation and severe colitis. This disease results from a reduced ability of dendritic cells to activate TGF-beta via integrin alphavbeta8. However, many crucial biological questions remain. Which types of dendritic cell are involved in this pathway? What is the role of this pathway at times of immune challenge? What happens to this pathway once the immune system has successfully eradicated an infection? This project will utilise conditional knockout mouse models to enhance our understanding of an important pathway in regulation of the immune system. Specifically, we will investigate the role of integrin-mediated TGF-beta activation in control of immune responses. This work will provide new insights into how the adaptive immune system is regulated at rest and in response to infection.999F0B31-F127-410A-A520-963B336BECE7Cell biology2859D39F6A-DEE0-4E48-8676-4C8374EF3C28Animal science72C8B14F2C-DED6-416E-BF1A-76A831488770Cells1492E358AA-AB7D-48F5-B189-8EC678DFF539Immunology722A0F6391-E88A-4396-9D63-25A68EEDA635Communication & signalling14