10067645REPOXYBLE: 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-C47AE53E333EUnclassified2934080Investigating the Regulation and Replication of R-loops at TelomeresActiveStudentshipMRCDivision of Cancer BiologyEukaryotic chromosomes are capped at each end by specialised nucleoprotein structures called telomeres, which are mutated or altered in essentially all incidences of cancer. Telomeres are transcribed into a non-coding RNA called TERRA, which forms a three-stranded R-loop structure in which the RNA remains bound to the template. R-loops are particularly prevalent at telomeres in ALT-type cancer cells, where they are thought to prevent efficient replication of the chromosome end. This project will identify novel R-loop regulating factors at telomeres and examine how TERRA-based R-loops regulate and influence the telomere replication process.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedEP/V000136/1Designing and exploring new quantum materials based on Fermi surface topological transitionsClosedResearch GrantEPSRCPhysicsAbstracts 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.34214018-FC7E-4A53-8E6E-05A78B30749ASupercond, magn. &quant.fluids70177C04BB-BFD4-4D65-BA9D-15A50728B8CAMaterials sciences30BEA752D6-11B4-4E5F-937C-2DD41104E229Materials Characterisation30D3193E46-72CF-4206-8EF1-1752747471B2Condensed Matter Physics70MR/W004291/1Research and Training to create assets in the form of new companies to develop a new model to generate innovative therapiesClosedResearch GrantUKRI Inn.ScholarDivision of Molecular PathologyCancer Research UK has partnered with Deep Science Ventures to create an opportunity for early career stage researchers to build ventures that target the complexity of biology. This partnership brings together the world's largest independent funder of cancer research with the unique venture design process of Deep Science Ventures to create a programme that is exhaustive in the search for the best approach from both technical and commercial perspectives, and positioned for new venture growth from day one. Their aim is to identify and bring together entrepreneurial scientists, academic advisors and investors to design and build new companies in oncology. In this project, the research goal is to develop therapies by leveraging the wealth of data of this new era to identify ways to kill cancer cells so that can escape from treatments. My role will be to start as a Founder Analyst within DeepScienceVentures under their unique framework for venture creation. It's a part-time role working mainly involving research. In order to make this research successful, I will apply my skills sets of machine learning/artificial intelligence, understanding heterogeneity, developing patient-based biomarkers and hands-on experience in preclinical trials. This also provides opportunity to get trained in market analysis, and customer development together with the DSV team before incorporating our own start-up.Cancer is an evolution machine. Decades before diagnosis, a multitude of different clones, carrying differential sets of mutations are setting the scene that makes almost any targeted therapy obsolete. The new era of personalised medicine and of immense knowledge of the genetics, epigenetics, gene expression, metabolomics, and clonal evolution of tumours, converges with the completion of flagship synthetic lethality studies, interrogating pan-cancer functional genomics. However, target discovery still focuses on finding targeted therapies against well-established cancer drivers from which cancer has already evolved out of, even years before diagnosis. This results in limited response rates in the clinic and quick evolution of resistance for targets against such drivers for example BRCA targeted PARP inhibitors. Our Approach: We are stopping the chase for moving targets by building a highly advanced drug discovery machine, that leverages the wealth of data of this new era to identify vulnerable mechanisms that cancer cannot evolve out of and the specific context in which they are effective. To achieve that, we identify cancer systems biology and specific mechanisms of irreversible cancer dependencies through advanced computational methods. Our current approach sets the bar very high, to produce complete and sustained therapeutic responses. We have invented methods that have already produced potential candidates with strong independent validation.My role will be to start as a Founder Analyst within DeepScienceVentures under their unique framework for venture creation. It's a part-time role. As a secondee, my goal is to join the host institution to create a company that will bring novel curative therapies to cancer patients. In order to make this successful, I will apply my skills sets of machine learning/artificial intelligence, understanding heterogeneity, developing patient based biomarkers and hands-on experience in preclinical trials.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified10107827CULTUral heritage in RurAL remote areas for creative tourism and sustainabilITYActiveEU-FundedHorizon Europe GuaranteeThe main objective of the project is to contribute to the promotion of cultural and creative tourism activities, considering the different capacities, resources, and specificities (material, creative, human...) of the territories, as a mean to help with the sustainable development of peripheral rural areas, favoring job creation and population settlement. For this, the potential of its cultural heritage will be researched, taking into account both the artisan material culture (techniques, materials, patterns and decorative elements), as well as the intangible culture (music, oral knowledge and culinary traditions) as a resource. To promote non-seasonal tourism as a form of sustainable development with a stable population settlement we are going to research the crafts linked to the territory and their implications, but we will also carry out a documentation of the productive processes. First and foremost, we are going to cater to the necessities of the local communities and pay attention to aspects related to societal groups at risk of exclusion, such as women, the elderly and the youth. All this will be developed from a multidisciplinary perspective, for which we will count on the various teams —most of them linked to different countries— that will be part of the consortium. Each of these partners will contribute to the development, as well as to the final result of the project through input directly related to their area of expertise: for example, among the collaborators we have intellectual teams specialized in the digitalization of heritage, research, or communication and dissemination, as well as as various institutions that will act as a testing ground for the more practical parts of the proposal. However, if something will characterize our work, it will be the constant collaboration between all parties, as well as the exchange of advice and experiences that will help to enrich collective knowledge and guarantee optimal results.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified82A7FD98-BACB-4676-8A7C-20ACBEBB958EUNIVERSITY OF ST ANDREWSLEAD_PARTICIPANT286866.0286866.0AH/V01241X/1ENGLISH HERITAGE TRUST CONSERVATION AND HERITAGE SCIENCE FACILITY - RANGER'S HOUSE, GREENWICH, LONDONClosedResearch GrantInfrastructure FundEnglish HeritageThe 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-C47AE53E333EUnclassifiedEP/D045304/1Novel Time-Resolved Thermal Imaging: AlGaN/GaN Heterostructure Field Effect TransistorsClosedResearch GrantEPSRCPhysicsThe increasing complexity of tasks required by communication, radar, aircraft, automotive systems benefits from the use of novel materials in high speed devices. Such devices, for example, radio-frequency (RF) transistors used in mobile communication base stations or phased array radars, have to meet certain performance standards. Electrical characterization is mostly used today to tackle challenges in the device development process to meet these standards. Electrical measurements, however, determine average device properties rather than specific information on spatial characteristics such as temperature and electric field inhomogeneities. If direct imaging of temperature and electric field distribution over a device area was possible with high time resolution this would open a new dimension for the investigation of semiconductor devices. This would be of great benefit to device researchers and developers to study and tackle time-dependent phenomena limiting device performance. Adequate techniques, however, are not existent at present. In the proposed work we will develop the first high-spatial resolution time-resolved thermal prober for semiconductor device imaging ever built to our knowledge. Electric field distribution will be extracted from the temperature information. The technique will be illustrated on the example of the topical AlGaN/GaN HFETs to learn more about how these devices operate in detail and what limiting factors for current devices are. For example, we will obtain information about carrier trapping related to AlGaN/GaN HFET current collapse, but experience shows that other interesting and potentially important discoveries are likely to result as well.50CC55CC-BE0D-4167-BD99-285D6BCC369BMaterials processing201908FDF5-1C61-4F33-B47F-3E91675C88AAInfo. & commun. Technol.55945E0A55-10CB-4E91-BCCB-7CB22CFE2232Tools, technologies & methods254D4F63B1-6DA2-42B3-AAF1-0FC07D91E3D3Instrumentation Eng. & Dev.258EC6A705-6D4A-44E8-95FF-27E262DA290CRF & Microwave Technology40811766AE-F6E0-4356-AEBF-17A4DA456AD4VLSI Design1550CC55CC-BE0D-4167-BD99-285D6BCC369BMaterials processing20EP/Y530037/1Open Access Block Award 2023 - Armagh Observatory and PlanetariumClosedResearch GrantOpen Access Block GrantFinanceAbstracts 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-C47AE53E333EUnclassifiedNE/P000061/1Characterising hydrothermal alteration across the Atlantis Massif: IODP Expedition 357ClosedResearch GrantNERCSch of Geog Earth & 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-D4707F62253BGeosciences100A646062E-6497-4533-8274-47644A7B369CEarth Resources207F1C4565-EFD3-4BE7-8A4A-B5F39FFD36F3Volcanic Processes302334C846-D357-4EF1-B929-0EC4EC1854CBHydrogeology40F52704F6-1035-4307-9FA9-45BC878F1F1ATectonic Processes10EP/H023666/1Ferroelectrics for Nanoelectronics (FERN)ClosedResearch GrantEPSRCElectrical, Electronic & 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.177C04BB-BFD4-4D65-BA9D-15A50728B8CAMaterials sciences2550CC55CC-BE0D-4167-BD99-285D6BCC369BMaterials processing251908FDF5-1C61-4F33-B47F-3E91675C88AAInfo. & commun. Technol.50BEA752D6-11B4-4E5F-937C-2DD41104E229Materials Characterisation2550CC55CC-BE0D-4167-BD99-285D6BCC369BMaterials processing252B23EFD7-00EA-4FCA-8685-A8B4B94BF976Electronic Devices & Subsys.50AH/I02352X/1Literary Mapping: Dickens and the Dynamics of PlaceClosedTraining GrantAHRCEnglish Language and LiteratureAlong with a large collection of nineteenth-century maps of London and topographical materials, The Museum of London (MoL) holds a series of 41 watercolours painted 1860-1870 by J.L. Stewart of 'real places' in Dickens's novels. The Bishopsgate Institute holds a further 60 Victorian watercolours of Dickensian places. Other holdings at MoL include paintings, panoramas, and stereographic images; the covers and illustrations of the serial parts of Dickens's novels; later book-edition illustrations; the archives of Dickensian tourism at MoL (and at the Dickens House Museum), including plans of 'Dickens Walks' and Victorian 'Dickens' souvenirs. MoL also holds significant theatrical collections and large collections of photographs of London. To mark the bicentenary of Dickens's birth in 2012, a major exhibition will run at MoL from December 2011-June 2012, with an international tour to follow. The student would use the exhibition as a significant research resource for thinking about the continuing fascination with the geography of Dickens's London. S/he would be involved in creating a 'Dickens Walk' for the exhibition, also delivered through an phone app, and in running and presenting at events connected to it, as well as in detailed evaluation of its visitor response. \nApplications will be invited which address some or all of the following research questions:\nWas Dickens the only author whose work was mapped so closely to the 'real' during -and after - his lifetime? (comparators could be Scott, Hardy, Wordsworth) \nHow does the map of Dickens's places change over the nineteenth century?\nHow does an ever more pervasive print culture generate new ideas of 'place' and create specific 'places'?\nHow does the representation of place in 'fact-based' articles in Household Words and All the Year Round compare to Dickens's versions in the novels? (Significant places might include: Newgate, bridges, coaching inns, law courts, London churchyards, the City, and what Dickens called 'fairy land': the places of entertainment and theatre). \nHow did Dickens's own travels affect his construction of the provincial and the global? (Locations which might be considered include: the cities of Boston in the US; Paris; Rome and its ruins, Rochester, Preston, Broadstairs). \nHow did Dickens's texts themselves travel? How did his American and/or colonial readers in his lifetime interpret his sense of place? \nWhat was the impact of photography, and -later- film, on the poetics of place and particularly of London? Conversely, what was Dickens's influence on filmic 'placing' - in the early films of Griffith and Eisenstein, for example?\nWhat happens to place when it becomes distanced in time? How do we reconstruct Dickens's places today? \nWhat have been the effects of the heritage industry and mass culture on Dickens's work?\nThere has been much debate about 'place' as historically contingent process in recent years. The thesis will engage with work generated by scholars of geography, history, literature and art, such as David Harvey; Nigel Thrift, Derek Gregory; Henri Lefebvre; Raymond Williams, Lynda Nead and Franco Moretti.\nThe student would have a hot desk space at MoL and access to all the graduate-student facilities at KCL. S/he would spend at least one day every week at MoL, and often more, particularly during the first year, in the run-up to and during the 2012 Dickens exhibition which will stimulate and feedback into the initial research. In years two and three the student will add value to the documentation around MoL's Dickens-related collections, in the light of his/her doctoral research, and will choose and curate a group of objects for an on-line exhibition in year 3 in line with the MoL's ongoing research strategy. Academic supervisions would be supplemented by meetings at least every two months between Werner, Pettitt and the stuDickens is exceptional as a literary figure who continues to excite immense international interest and his bicentenary in 2012 will generate considerable media attention. Both Werner and Pettitt are experienced in giving media interviews and dealing with the press (Pettitt was interviewed on Radio 4's Today Programme, among others, about her last book; and Werner regularly speaks to the press) and are well-placed to capitalise on these opportunities, and maximise the media exposure of both the exhibition and the connected research at MoL.\n\nPettitt is planning a new undergraduate course on 'Dickens and London' inspired by this project. The beneficiaries of the collaboration will include but will also extend well beyond students (UG/PG) and academic staff at KCL and Museum staff at MoL. They will include a wide variety of museum/exhibition visitors, both 'real' and on-line, such as school children, adult learners, academics and journalists, and we expect international impact, both through tourists attending the exhibition and its supporting events, and, in the longer term, through hits on the legacy 'Dickens exhibit' website. \n\nThe student will also be involved in organising and presenting at a series of exhibition-related events, some at the MoL and some at KCL which will be free and open to the public. KCL has a new partnership with Cheltenham Literary Festival so a Dickens event could appear on the 2012 Festival programme too.\n \n'Literary Mapping: Dickens and the Dynamics of Place' will provide new insights into London's past, helping to inform the public histories presented by the Museum in its displays, online and through other outputs. The Museum recently created one of the most successful phone apps interpreting London's historic topography (Streetmuseum), and the student will be well placed to build on this and help the Museum deliver another innovative resource that will reveal the London of Charles Dickens to the general public. Considering the worldwide interest in the works of Dickens, such a resource is likely to have a broad appeal both to national and international visitors as well as those who live and work in the capital, and the intention is to deliver it in a range of languages. It will impact on the Museum's marketing campaign in drawing people to the exhibition (the target has been set at 100,000 visitors between December 2011 and June 2012). It will have a financial impact by increasing revenue for the Museum and other related attractions and sites across London.\n\nThe student's work will demonstrate the potential of the Museum's collections as a research resource and add value to the Museum's existing body of knowledge about its collections. The delivery of an online exhibition around the Museum's Dickens-related collections will create a further publicly accessible output and contribute to the Museum's reputation as a national and international resource on London and, in this case, specifically about literary London in the nineteenth century. It will also form part of the MoL's ongoing commitment to defining itself as a rich research resource both for scholars and for the public.\n\nCrucially, though, the impact of this project will not be only 'one way' - pushing outwards from the MoL towards the public. It will also close the loop and feed back the responses and ideas of the public into MoL's on-line displays. The student will have the opportunity to do this both through devising creative ways of eliciting reactions and responses at the exhibition from different constituencies of visitors, and through the detailed evaluation of this visitor response, and its use in considering the meanings of 'Dickens' to different interest-groups.\n\nThis innovative collaboration between curatorial and academic specialists has the potential to deliver both a highly stimulating doctoral apprenticeship, and6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedBB/F014279/2Regulation of protein synthesis as a mechanism of nutritional programming and developmental origins of optimal healthClosedResearch GrantBBSRCMRC Toxicology UnitThe diet of an individual can have important health consequences at any stage of life. However there is evidence to suggest that the diet of women during pregnancy and while breastfeeding is particularly important as it has major long-term implications for the health of her baby. It has been shown that individuals with a low birth weight are not only less likely to survive delivery but are also at substantially increased risk of developing type 2 diabetes, high blood pressure and heart disease in adulthood and are more likely to die at a younger age. The underlying causes of the relationship between early growth and adult disease are not known, but it is thought that the quality of the diet of women during pregnancy and breastfeeding is critically important. Studies in animal models can be very useful in helping to decipher mechanisms of human diseases. We have shown that if pregnant and lactating rats have too little protein in their diet their offspring are small at birth and later develop diabetes. We have studied fat tissue and have identified key proteins that are much less abundant both in young men who had a low birth weight and in offspring of protein restricted rat mothers. The central dogma of biology is that the genetic material DNA is copied to an intermediary molecule RNA that is then translated into proteins. Our recent results suggest that the second step of this process is permanently altered (or 'programmed') in the offspring of animals or humans that had a sub-optimal diet. In our project we will study RNA from rat and human fat cells to identify new genes that are programmed to be expressed at different levels as a result of poor early life nutrition. We will also determine why it is that their RNA is not translated properly to make the corresponding proteins. Understanding these processes will enable us to identify individuals at risk and to develop intervention strategies to improve the health of pregnant and breast-feeding women and their offspring.Fetal and early life nutrition has long-term (ie programmed) consequences for health. This has been termed the Developmental Origins of Health and Disease. Despite numerous studies confirming the concept of nutritional programming and its associations with long term health, the molecular mechanisms by which a phenomenon that occurs in utero or during very early life has phenotypic consequences many years later are poorly understood. This proposal addresses the fundamental underlying molecular mechanisms of nutritional programming. We hypothesise that programmed responses to sub-optimal nutrition in early life are significantly mediated by regulation of gene expression at a post-transcriptional level. We further hypothesise that diet-induced changes in regulatory factors such as miRNAs alter cellular memory and consequently impact on long term health of the organism. We will adopt an integrated approach to test these hypotheses, combining whole body nutritional programming, functional genomics and transcriptomics using both the well established maternal low protein rat model and human biopsy material. This will include both genome-wide and gene-specific analysis of adipose tissue. Understanding the mechanisms involved in nutritional programming could ultimately lead to diagnosis, prevention and treatment of the long term effects of diet on health.88E467D8-9675-4A34-981C-F517896062B4Genetics & development2529F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies12999F0B31-F127-410A-A520-963B336BECE7Cell biology121D119F53-9239-4168-85B9-6DE4EE0B48D0Food science & nutrition512A0F6391-E88A-4396-9D63-25A68EEDA635Communication & signalling12937A9F23-021A-4604-8979-A28E0E04F825Transcriptomics1223DCA711-FFA6-4DCF-A65B-9A8B653571ECGene action & regulation253ADE3DAF-6018-4A3F-98C6-BDBB393095F4Diet & health51ST/M00161X/1ISOL-SRS: ISOL Beam Storage Ring SpectrometerClosedResearch GrantSTFCPhysicsAbstracts 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.Knowledge transfer: We foresee a number of areas where knowledge transfer could occur. All detectors used with the external solenoid must operate successfully in high magnetic field. In particular, we have highly pixellated silicon detectors. The challenges making these highly-integrated detectors function in this environment are extremely close to the demands of combined PET/MRI or SPECT/MRI, seen as a high priority for medical imaging in the future. Highly integrated electronics and ASICs may also be transferred over to the medical or other relevant sectors. The detectors to be used inside the storage ring must survive baking out to high temperatures and be compatible with very high vacuum. This may have applications to other areas of science. In the exploitation phase, the ISOL-SRS system could be used to gather nuclear data relevant to fission reactors, decommissioning or future fusion reactors. A specific example is the ability to measure beta-delayed neutron branches of ions stored in the ring. All the groups have a strong background in knowledge transfer. The Liverpool and Daresbury groups have experience in transferring nuclear physics detector technology towards the medical sector in areas such as SPECT imaging. York established an industry-facing detector development laboratory working on coupling scintillators to novel photosensors. Manchester has the Dalton Institute in-house who provide a natural linkage to the nuclear energy sector, while Surrey have a diverse group working in applications. Manchester, York and Surrey working on nuclear data relevant to present and future fission reactors, supported by an EPSRC grant. Knowledge transfer may be facilitated between groups and companies concerned with applications in nuclear measurement techniques and instrumentation, including GE Healthcare, BAE Systems, AWE, Canberra, Centronic, Kromek, Canberra Harwell UK, Ametek (Ortec), John Caunt Scientific, National Nuclear Laboratory (NNL) and Rapiscan. Liverpool has a 4 year STFC IPS Fellowship to maximize the impact of the STFC science portfolio. The Fellow will work closely with Liverpool, STFC Daresbury Laboratory and the Cockcroft Institute for Accelerator Science. The role will deliver increased numbers of industrial studentships, enable "pump priming" of collaborative ideas through appropriate routes such as mini-IPS or mini-KTP projects and will facilitate potential staff exchanges with industrial collaborators. The Edinburgh Nuclear Physics Group has been at the forefront of nuclear physics applications of silicon strip detectors since this technology became commercially available. They have a long-standing relationship with the UK company Micron Semiconductor Ltd (MSL). With MSL, they have developed silicon strip detector designs with very thin (~20 micron) and thick wafers (~mm) for our research applications. MSL now has a range and depth of technical capability unmatched by any commercial company worldwide and this technology is now applied to X-ray and space-based applications. Public engagement: There is considerable scope to engage with a variety of general audiences from schoolchildren to the wider public. Big science like nuclear/particle physics and astronomy is acknowledged as one of the key motivators for young people to decide to study Physics at university level and for a career. This project has an inspirational story attached relating to our fundamental understanding of nuclear structure and our understanding of the origin of the chemical elements. We are developing new instrumentation for the world's most famous scientific laboratory. The test bed solenoid magnet has featured in an article in New Scientist. Ongoing educational initiatives include Nuclear Physics Masterclasses for schoolchildren held at Surrey, Liverpool and York, supported by outreach officers co-funded by the Ogden Institute. Public engagement work will be facilitated by the STFC outreach officer, Elizabeth Cunningham.8C77C51A-5639-42DA-B4F4-4A184CA2EA00Nuclear physics100A4CEBAA4-8692-41A1-89CB-E92E7854929ENuclear Structure505333CE47-4782-4D31-A764-62C2F6914101Nuclear Astrophysics50BB/K002341/1Exploiting natural product assembly line genomics and synthetic biology for discovery and optimisation of novel agrochemicalsClosedResearch GrantBBSRCChemistryMicroorganisms including bacteria and fungi are everywhere in the environment. Although a few microorganisms have roles in causing disease, most microorganisms are harmless, and many of them actually produce medicines and chemicals useful to man. A good example is penicillin which is produced by a fungus and used as an effective antibiotic in human and animal medicine. Other compounds include anticancer drugs, drugs which allow organ transplants by suppressing the immune system and anticholesterol drugs. Many microbes also produce compounds of huge importance in agriculture which can be used as insecticides, herbicides and fungicides. It is estimated that around 40% of current world food productivity would be lost without these. As the world population grows and as climate change takes hold efficient food production and food security will become more important and the roles of these naturally occurring compounds will increase yet further. Penicillins came into use during the 1940s, and for around half a century research provided a steady stream of newly discovered natural products. However, traditional approaches began to fail as more and more compounds were discovered because the available methods kept finding the same known compounds. This led companies to try other avenues to provide new compounds for use as medicines and agrochemicals - however fully synthetic compounds have not proven as successful as natural products. Over the past decade academic research, much funded in the UK by BBSRC, but also an international effort, has led to the understanding that most microbes have the capacity to produce very many more compounds than observed - perhaps only 10% of a given organism's potential has been collected to-date. Genome sequencing has revealed that the biosynthetic potential of known organisms is huge - and new organisms are continually being found. If the 90% of unused genes in just the known organisms could be activated there could be a strong flow of new compounds for testing as medicines and agrochemicals - this flow could be increased to a flood if a generic technology could exploit all the as-yet undiscovered microbes. In parallel with the genome sequencing efforts huge progress has also been made in understanding the genes, enzymes and chemistry involved in the microbial synthesis of secondary metabolites. This now allows the pathways responsible for the synthesis of secondary metabolites in microbes to be engineered to produce yet more compounds. The confluence of cheap whole genome sequencing and the ability to engineer microbial pathways underpins this research proposal. The project will be a collaboration between 6 partners: the Challis group at Warwick, expert in microbial genome analysis; the Leadlay group at Cambridge, expert in bacterial polyketide biosynthesis; the Micklefield group in Manchester, expert in bacterial peptide production; the Cox group in Bristol expert in fungal biosynthesis; and Syngenta and Biotica, UK companies with major interest in secondary metabolites. We will obtain the genome sequences of bacteria and fungi known to produce agrochemically useful compounds. We will find the genes responsible for their production and recombine and engineer them to make higher amounts of these compounds, and then libraries of related compounds for testing. We will work with partners in the international agrochemical company Syngenta to develop these as new herbicides, insecticides and fungicides, while partners at the Biotechnology company Biotica will focus on compounds with use in human medicine. Overall we aim to develop a platform technology which can exploit the potential of microbes for the production of useful compounds for use in agriculture and medicine. We will also disseminate our results widely and undertake outreach activities to increase public awareness of industrial biotechnology and the role of genetic engineering and microbiology in ensuring future food security.This project will exploit a major opportunity which has arisen due to three factors: the dramatic lowering in cost of microbial full genome sequencing; the recent advances in rational engineering of microbial metabolic pathways; and the re-emergence of interest in natural products as new agrochemicals and drugs by international companies. The project will bring together 6 partners: the Challis group at Warwick, expert in genomics-based natural product discovery; the Leadlay group at Cambridge, expert in bacterial polyketide biosynthesis; the Micklefield group in Manchester, expert in bacterial nonribosomal peptide bioengineering; the Cox group in Bristol expert in fungal biosynthesis; and Syngenta and Biotica, UK companies with major interest in secondary metabolites. The collaboration will allow the 6 partners to embark on an ambitious programme to rapidly sequence the genomes of 40 microorganisms with the known ability to produce compounds with potential in the agrochemical arena. New bioinformatic methods will be used to rapidly identify biosynthetic gene clusters and link them to the synthesis of particular compounds. Engineering will then be employed to increase titres and activate 'silent' gene clusters with potential to produce bioactive compounds. Focussed libraries of target compounds will be made by biosynthetic engineering and the libraries used for SAR by Syngenta. Compound activity will then be maximised by a combination of biosynthetic engineering and synthetic chemistry. The partners will also engage in dissemination, training and outreach activities designed to maximise the impact of the project in the academic, industrial and public communities.Short term: The project will have high impact with the directly involved partners. For the companies involved it will allow them to gain access to and exploit the significant pool of knowledge and experience within the UK academic community in the area of biosynthetic engineering and synthetic biology. In particular this will help give Syngenta a competitive advantage and maintain their significant research and employment base in the UK. It will have a significant impact for the 4 academic groups involved because it will allow them to collaborate and disseminate best practice in complementary areas of research - this is likely to lead to more publications and publications of higher impact and thus help maintain the UK's competitivity in this area. It will help the academic groups focus their efforts on the development of new products and bring knowledge and experience from commerce into the academic arena. This in turn will enable the academic groups to form new and effective collaborations. Medium term: The research has a good likelihood of leading to the development of new products with utility in the agrochemicals sphere which will underpin improvements in food security internationally. The project will train at least 8 PDRAs and up to 4 students in the area of synthetic biology as applied to industrial biotechnology. These people will form a core of expertise which will benefit both academia and industry. Long term: The development of a platform technology for the systematic exploitation of microbes for the development of new medicines and agrochemicals will form the basis for the development of new technologies using synthetic biology. For example it is likely that similar methodology will underpin the development of new materials, new fine chemicals and processes, new methods to access biofuels and new methods to access foodstuffs.2D9083F0-05FA-4726-9EB2-3FCC293CAAF9Biomolecules & biochemistry604CCA4C04-0C28-41BE-8869-FA6391A7F005Microbial sciences406D0F40FF-D03E-4429-A764-185BC521A840Catalysis & enzymology606997E843-AD07-4064-B67D-D4A928309DB4Biochemistry & physiology40AH/G015198/1EGOR: Environmental Guidelines: Opportunities and RisksClosedResearch GrantAHRCCollection CareThis research cluster will bring together a team of key professionals, academic researchers representing AHRC/EPSRC disciplines as well as heritage practitioners to appraise the costs and risks of current environmental guidelines for cultural heritage in response to a changing climate. This theme has a national and international dimension since climate change, energy consumption, visitation and pressures for greater access to collections will continue to make considerable demand on cultural heritage in the 21st century globally. The scale and pace of these changes are posing unique challenges to managing the long-term preservation of material culture and are the focus of discussion amongst professional communities both nationally and internationally.This research cluster will inform this debate.\n\nCurrent environmental parameters and tolerances set out in national and international guidelines and standards as well as Governmental Sustainable Development Targets play a critical role in shaping practices in the cultural heritage sector such as building construction, and environmental management. This includes the control of temperature, moisture, light and pollution - the main factors affecting the conservation of material culture. Environmental guidelines impact significantly on how collections are stored, accessed, loaned and displayed. \n\nEqually, the cultural heritage sector is not immune from the challenges posed by global responsibility: reducing reliance on fossil fuels, changing behaviours in favour of re-use and alternative energy sources, for example. It is within this context the appropriateness of current environmental guidelines designed to meet an agreed standard for managing material culture change, enable visitors to access and experience collections to a seasonal standard of comfort, and provide access to collections both locally and internationally is being questioned as the 'costs' of this are being realised. Unfortunately, there are no easy or headline-grabbing answers to this problem: the risks need to be identified, the costs understood, the options appraised. \n\nEGOR will provide the necessary framework to develop thinking in this area in order to realise an intellectual step change in understanding the risks and uncertainties of current environmental guidelines, standards and targets in a changing climate. Consideration will be largely focused on indoor environments, collections and the people who engage with and work in the cultural heritage arena, and will build on foundations established by other research projects e.g. Noah's Ark (EU), Engineering our Futures (EPSRC), Living with Environmental Change (NERC) largely focused on climate impacts outdoors. This will be achieved through 5 sequential activities: \n1. An inaugural meeting of the steering group which includes professional leaders, and named investigators to shape thinking and initiate cross fertilisation of ideas and perspectives;\n2. 3 working group meetings comprising specialists in art history, engineering, material science and conservation for coherent discussion, and lively debate to understand the implication for current environmental guidelines in a changing climate for people, their values and history, buildings housing collections (often historic structures themselves) and collections. The implications will be considered against a background of global responsibility.\n3. A two-day residential event will conclude this investigative process; the three working groups will present their findings, areas of convergence and divergence will be further debated to determine the risks and uncertainties surrounding environmental guidelines and standards in a changing climate, and the outstanding research needed to fully inform this debate.\n\nA summary of the challenges and user-led research emerging within this theme will be reached at the end of the meeting and presented at the Programme conference in July 2009.2693EEB1-BEF5-45C6-999E-D56488EFFAD7Cultural & museum studies10077E870DC-ED98-44DF-A0C8-06A874EB34A2Cultural Studies & Pop Culture10010057221A 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_PARTICIPANT1560910.01092637.0BB/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 biology2529F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies13945E0A55-10CB-4E91-BCCB-7CB22CFE2232Tools, technologies & methods12812BD191-6D4F-4F72-852D-0F63AD58ABD8Research approaches12EF22E4A7-F12A-4859-8A95-E0179E3570ECBiological membranes122A0F6391-E88A-4396-9D63-25A68EEDA635Communication & signalling136D0F40FF-D03E-4429-A764-185BC521A840Catalysis & enzymology13937A9F23-021A-4604-8979-A28E0E04F825Transcriptomics13CA10DA58-174F-4FE6-B61B-8EEBFB8192E2Receptors122928626Characterising 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-C47AE53E333EUnclassified10037439Eye 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 PLCPARTICIPANT0.00.0614B0FA0-9759-4C48-A17A-E167CDB4424BNATIONAL GRID ELECTRICITY TRANSMISSION (NGET)LEAD_PARTICIPANT0.00.0F1B6C800-F277-46F6-8183-9B07CBF77E6ESPOTTITT LTDPARTICIPANT0.00.0CD432890-34DA-454F-90BE-D3033081FEEADNV SERVICES UK LIMITEDPARTICIPANT0.00.0