EP/Y004663/2Quantum Algorithms for Nonlinear Differential Equations - QuANDiEClosedResearch GrantEPSRCSch of EngineeringAbstracts 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-C47AE53E333EUnclassified710397Wittos - 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_PARTICIPANT165589.090461.0BBS/E/I/00001302Role of avian dendritic cellsClosedInstitute ProjectBBSRCUNLISTEDAbstracts 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.The UK poultry industry faces many challenges to remain sustainable, including moves to more extensive rearing systems; withdrawal of antibiotics and other drugs such as anti-coccidials; resistance and residue problems with anti-helminthics. These will all impact on poultry health, but also the potential to impact on human health. Increased incidence of zoonotic pathogens in chickens, such as avian influenza, could lead to an increase in these diseases in man. One approach to these challenges is to develop novel and more effective vaccines. For this to be a realistic and sustainable approach, we need a better understanding of host-pathogen interactions in chickens. This proposal seeks to build on our unique capability to grow dendritic cells (DC) in a non-mammalian species. DC in mammals are professional antigen presenting cells, providing a link between innate and adaptive immune responses, driving the adaptive response to that necessary to clear infection with a particular pathogen. In mammals, antigen presentation takes place primarily in lymph nodes (LN). The chicken, like most non-mammalian vertebrates, lacks LN but antigen presentation still occurs. This proposal forms part of our efforts to understand antigen presentation in a species lacking LN. This proposal aims to understand DC biology in the chicken in more depth. Firstly, we wish to define the phenotype of DC, both immature DC and those matured in vitro under different conditions, in more depth. In mammals and presumably in the chicken, DC travel to the site of infection, and thence to the site of antigen presentation, under the influence of chemokines. We intend to determine which chemokines have functional effects on chicken DC. Preliminary data suggests that DC can be matured to either a Th1 or TH2 phenotype. We will determine if DC can bias T cells to a Th1 or Th2 phenotype in vitro. We then want to characterise ex vivo-isolated DC, and finally begin to analyse chicken DC migration in vivo.unavailable6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedBB/V002007/1Probing the structure and function of a super-rogue photosystem II complex involved in chlorophyll f synthesisClosedResearch GrantBBSRCLife SciencesThere is an urgent need to develop new strategies to improve crop yield to feed the ever-growing global population. Crop plants grow because they use the energy of sunlight to drive the conversion of atmospheric carbon dioxide into biomass. This process of photosynthesis is relatively inefficient with much less than 1% of the incident solar energy converted into stored chemical energy. One straightforward way to improve photosynthetic efficiency is to capture more of the sunlight in the first place. Plants rely on chlorophyll pigments (as well as some accessory pigments) to absorb light to drive photosynthesis. The chemical nature of the chlorophyll pigments found in plants necessarily means that photosynthesis is restricted to the visible region of the solar spectrum. In recent years, however, several strains of cyanobacteria, which perform plant-like photosynthesis, have been discovered that make modified forms of chlorophyll that absorb light in the far-red region of the spectrum. If these far-red chlorophylls could be made in plants and assembled correctly in the photosynthetic apparatus, the number of photons of light that could be used to drive photosynthesis could be increased by up to 19%, a considerable increase in efficiency. One of the far-red absorbing chlorophylls is chlorophyll f (Chl f). In order to make Chl f in plants, an important first step is to identify and characterise the cyanobacterial enzyme that synthesises Chl f. In a recent breakthrough, Don Bryant and colleagues in the USA showed that Chl f synthesis was dependent on the ChlF protein subunit which, somewhat surprisingly, was found to be related to one of the proteins present in the well-studied photosystem II complex which catalyses the light-driven oxidation of water to oxygen characteristic of plant photosynthesis. In follow-up work, we have discovered that ChlF does not act alone, as was originally thought, but is part of a new type of PSII complex, which we term the super-rogue PSII complex. The super-rogue PSII complex shows clear similarities to regular PSII but has evolved to make Chl f rather than split water into oxygen. Chl f is made from the Chl a pigment through an oxidation reaction involving molecular oxygen; but the chemistry involved in this process is currently unknown. In this application, we propose to study the structure and mechanism of the newly identified super-rogue PSII complex in unprecedented detail. We aim to investigate whether the super-rogue complex is photochemically active and will test the hypothesis that the super-rogue PSII complex activates molecular oxygen into a reactive form that oxidises a Chl a molecule bound to a specific site in the super-rogue PSII complex. The project involves a team of scientists with skills in microbiology, molecular biology, biochemistry and spectroscopy. Our experimental approaches are diverse and involve working on biochemically pure protein complexes as well studying cyanobacterial mutants expressing Chl f. Ultimately our studies will provide important new knowledge on a new type of photosystem II complex that will underpin future work producing Chl f in crop plants.Synthesis of chlorophyll f (Chl f) in cyanobacteria requires the expression of the ChlF subunit, a paralogue of the D1 subunit of oxygen-evolving photosystem II, but the mechanism remains unclear. In background work we have discovered that ChlF is able to substitute for D1 to form a modified PSII complex with a role in Chl f synthesis rather than water oxidation. We have named this complex the super-rogue PSII complex (or sr-PSII). We have also identified a QD sequence motif in ChlF that is important for Chl f synthesis and possibly the binding of Chl f. To clarify the role of sr-PSII in Chl f synthesis, we propose to: (1) determine the co-factor composition of the sr-PSII complex; (2) use time-resolved absorbance and fluorescence spectroscopies to characterize its photochemical activity; (3) probe the presence of the potential Chl f-binding site by monitoring changes in the optical properties of variant sr-PSII complexes in which the axial His ligand or the QD residues that are predicted to H-bond to the formyl group are mutated; (4) test the possible involvement of reactive oxygen species in Chl f synthesis (5) establish an in vitro system for Chl f synthesis using either the isolated sr-PSII complex or membranes containing sr-PSII to help assess catalytic parameters of the enzyme and (6) test whether heterologous production of Chl f is enhanced by expressing the native 'far-red' PSII subunits of Chroococcidiopsis thermalis which are known to bind Chl f. In parallel we will (7) isolate FLAG-tagged sr-PSII from C.thermalis to assess whether the native system contains additional protein components and then use mutagenesis to confirm the importance of the QD motif in the native system. Overall this work will provide new insights into the synthesis of Chl f which will be important for future work aiming to introduce Chl f into the photosynthetic apparatus of plants as a strategy to enhance photosynthetic efficiency.Understanding the details of Chl f synthesis might in the long-term lead to the development of microalgae and plants with more efficient photosynthesis, especially in far-red enriched environments, such as the lower regions of the canopy, or in dense cultures of algae. In the agricultural sector, beneficiaries could include: companies involved in modifying or selecting plants to maintain and or improve crop yields; farmers who wish to develop new practices for similar reasons; governments and policy-makers interested in developing novel strategies to achieve food security; and the public who will benefit from food security. In the biotechnology sector, beneficiaries include companies who wish to develop microalgae and other related photosynthetic organisms as solar biorefineries for the sustainable production of green chemicals and high-value products. In the bioenergy sector, beneficiaries include: companies wishing to develop alternatives to fossil fuels; governments and policy makers who are interested in new routes to energy security and for new energy sources for developing countries; the military who are looking for alternative fuels for specific and niche uses; environmentalists who need to focus on rational long-term alternatives to fossil fuels. In the environmental and ecological sector, beneficiaries include those wishing to understand more about the role of chl f-producing cyanobacteria in a changing environment. In the education sector, in museums and in the media, there will be benefits from publicising new advances in photosynthesis, one of the most fundamental biological processes and one that has been taught at secondary school and so readily familiar to the general public. Staff hired for the project will obtain training in cutting edge research in world-leading research centres. Peter Nixon and James Murray are members of the Photosynthesis Research Lab at Imperial College which includes world leading experts in Photosynthesis including Bill Rutherford FRS and Jasper van Thor, with expertise ranging from femtosecond spectroscopy to cyanobacterial physiology. The PDRA and technical staff will be in an excellent position to progress their careers. They will have the benefit of the excellent intellectual environment of a leading university with a tradition of close ties with engineers and industry.2D9083F0-05FA-4726-9EB2-3FCC293CAAF9Biomolecules & biochemistry484CCA4C04-0C28-41BE-8869-FA6391A7F005Microbial sciences2452C19A61-0A59-4643-A8D3-583E9A7F811APlant & crop science2419F550D7-1AE6-4B86-87B9-2C2934306C34Environmental Physiology246997E843-AD07-4064-B67D-D4A928309DB4Biochemistry & physiology483D51C146-5AFC-42C5-93BB-17CC751DE0DABioenergetics24MR/W000830/1A CELL ATLAS OF THE DEVELOPING HUMAN SENSORY NERVOUS SYSTEM: INVESTIGATING DEVELOPMENT TO UNDERSTAND DISEASEClosedFellowshipMRCCellular GeneticsContext of the research: Pain is the main reason that diseases of the muscles and joints lead to disability. In particular, for the tens of millions of individuals who suffer from Osteoarthritis (OA) , pain can be debilitating at end stages and be present even at rest, preventing the use of joints in the hand, hip and knees. Around the world, this tremendous societal and monetary burden is set to rise alongside an aging population. Currently, there is no cure for osteoarthritis and end stage disease is treated with joint replacement, a costly and major operation. Importantly, we lack effective pain-relief medications for OA. Until recently, it was thought that wear-and-tear of the protective lining of the joint, and increased bone-to-bone contact is what leads to pain in disease. Interestingly, recent studies from various research groups have shown that new nerves sprout into the joint surface as part of the disease process of OA. These nerves appear to be present in individuals with painful OA, but is absent in those with less painful OA. In adulthood, nerves normally have limited capacity to grow, so this leads us to think that disease nerves are driven by processes similar to those that are active when we our nervous system begins to develop while an embryo in the womb. The objective of this project is therefore to apply cutting edge technology to investigate the development of the human sensory nervous, comparing it to what happens in disease, with the aim of identifying novel ways of interfering with it, in order to treat pain. Aims and objectives: First, we aim to understand how the sensory nervous system forms in the developing human. To achieve this, we will use single-cell sequencing technologies. This will allow us to detect what drives different types of developing nerves, one by one. We aim to form a classification system for these nerves, sorting them by their function, for example, some nerves may sense touch and others may sense pain, and they might be driven by different signals to grow. Secondly, we will map the distribution of these developing nerves in space, using a type of technology known as spatial transcriptomics. This will form an atlas of the nerves throughout the body and allow us to understand how nerves are queued to grow towards their destination during development. Then, we will map nerves in the diseased human osteoarthritic knee joint in adulthood. We will apply innovative technologies to first identify areas where nerves are present, and then sequence the genes activated within these areas. This will allow us to understand whether nerves growing in disease are similar or different to nerves that grow during development.Lastly, we will use computational programs to compare developmental nerves to disease-nerves. This will allow us to decide how to target the disease-nerves. Potential applications and benefits: We will be the first group to perform single-cell sequencing on the developing nervous system in human. This will allow discovery of new cell-types, and create an atlas for them throughout the human body. These findings will further our understanding of all painful conditions. In the case of osteoarthritis, it may allow us to identify targets that can be exploited to allow depletion of the pain-associated nerves described above. We aim to disseminate our findings to allow public access by the research community. This will lead to improved understanding of other diseases, such as in cancer, where nerves can also sprout during the disease process. In the long term, our findings can also be applied to help improve models of nerves grown in the laboratory, and potentially also inform ways of promoting nerves to regenerate in the body.I aim to test the hypothesis that the process of neo-innervation of the adult osteoarthritic joint by pain-associated nerve afferents recapitulates transcriptional profiles that are active in the developing human fetal sensory nervous system, with a view to obtain mechanistic insight, and identify potential therapeutic targets for pain. First, I will create the first human cell atlas (HCA) of the developing sensory nervous system. Secondly, I will identify the transcriptional profiles of adult osteoarthritic joint cartilage that is innervated by pathogenic nociceptive afferents (absent in the osteochondral junction in health). Finally, I will compare the transcriptional profiles in these states to test our hypothesis, and additionally prioritise potential treatment targets. Single-cell RNA sequencing(scRNAseq) will be applied to human dorsal root ganglia samples between the fetal ages of 6 to 20 weeks, with 1-2 sample(s) each gestational week. To create a spatial atlas, single-nuclei RNAseq and Visium RNAseq (10X genomics) will be applied to sequential slices of the same tissue sample at ages of 6-7 weeks and 18 weeks. In adult osteoarthritis tissue, multiplex in situ hybridization will be used to identify regions of interest by neuronal markers followed by the use of Nanostring GeoMx for targeted sequencing. Finally, computational integration will be applied to reveal reciprocal matches in cell states between development and disease. Potential treatment targets will be tested in further projects through in vitro and in vivo experiments. The study will create the first HCA of the developing nervous system and transcriptional profiles of disease, the findings will provide new insights into normal human development as well as disease, with therapeutic implications. The developmental dataset can also be studied to understand nerve regeneration in adulthood, with implications in regenerative medicine, and in generating in vitro models of sensory nerves.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified2444772Post-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-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-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-C47AE53E333EUnclassifiedBB/N022041/1Cuba: Application of 'omics in the metabolic study of high cell density continuous cell cultures of recombinant NS0 myeloma cell linesClosedResearch GrantBBSRCChem Eng and Analytical ScienceAbstracts 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/D01087X/1The evolution of parasitic sex ratio distortionClosedResearch GrantNERCSch of Biological SciencesHost-parasite interactions are pervasive throughout the natural world, forming a critical component of plant and animal communities. Among them, parasites that distort host sex ratios are widespread in invertebrates. The effect of sex ratio distorters can have a powerful effect on biodiversity; they can cause populations to become extinct and change the composition of animals in the community. Additionally as they can affect harmful as well as beneficial hosts, there is currently a great deal of interest in the use of such parasites for biological control. Sex ratio distortion has evolved in diverse parasites (eukaryotes and bacteria) and affects diverse hosts. Why distort sex ratio? These parasites are passed from mother to offspring in the eggs and are only transmitted by females. These parasites have evolved a number of strategies to increase the relative frequency of female hosts (so increasing the spread of the parasite). Feminisation is induced by the bacterium Wolbachia and by microsporidia (eukaryotic parasites) in Crustacea. In contrast Wolbachia causes male killing in insects. Discovering the mechanisms of male killing and feminisation is key to understanding host-parasite coevolution. We propose that these intracellular parasites are most likely to act by secreting molecules into the host cell which will then influence host molecular pathways, they may modify the response to external hormonal signals or even induce programmed cell death (apoptosis). Such changes could disrupt patterns of sexual development or lead to sex-specific embryo mortality. AIMS: We will investigate the evolution of sex ratio distortion in distantly related parasites by testing the hypotheses that - Similar mechanisms lead to contrasting strategies of sexual manipulation by Wolbachia (male killing in insect hosts, feminisation in crustacean hosts) - Parallel mechanisms of feminisation have evolved in distantly related parasites (Wolbachia and microsporidia) OBJECTIVES I. WE WILL INVESTIGATE THE MOLECULAR BASIS OF WOLBACHIA INDUCED MALE KILLING AND FEMINISATION. We will use state of the art techniques (proteomics) to identify molecules secreted into the host cytoplasm that cause feminisation or male killing, and to follow the changes they induce in the host. We will study this initially in the Drosophila (fruit fly)/Wolbachia male killing system. The genome of both these organisms is known and will help us to identify proteins and their function. We will then go on to study feminising Wolbachia in the crustacean Armadillidium vulgare (woodlouse). II. WE WILL INVESTIGATE THE CELLULAR BASIS OF WOLBACHIA AND MICROSPORIDIA INDUCED FEMINISATION BY TESTING FOR MANIPULATION OF THE PATTERN OF CELL DEATH IN THE DEVELOPING HOST Parasites cause feminisation in Crustacea by inhibiting development of the androgenic gland (the gland that controls male sexual differentiation). To pinpoint the site of action, we will map the distribution of feminising microsporidia and Wolbachia during sexual differentiation of their crustacean hosts. We have recently observed an association between male killing in Drosophila bifasciata by Wolbachia and apoptosis (programmed cell death). We will test whether feminising parasites also induce apoptosis in the androgenic gland in order to feminise the host.88E467D8-9675-4A34-981C-F517896062B4Genetics & development5029F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies50145958A0-DF76-40F3-A919-A64B4E16E540Population Genetics/Evolution50C6A85141-ED79-4266-86E5-F6D25217C97FEnvironmental Genomics50BB/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 sciences406997E843-AD07-4064-B67D-D4A928309DB4Biochemistry & physiology406D0F40FF-D03E-4429-A764-185BC521A840Catalysis & enzymology60AH/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 Culture10010067645REPOXYBLE: 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-C47AE53E333EUnclassified2119089Microbial Interactions Within Denture BiofilmsClosedStudentshipBBSRCDentistryMost microorganisms naturally grow within biofilms in both environmental and industrial systems. Biofilms on denture surfaces are widely acknowledged and arise in cases of poor oral/denture hygiene and where dentures are not removed whilst sleeping. Key microorganisms in denture biofilms include fungi of the genus Candida as well as bacteria that can originate from other oral sites or from exogenous sources. The majority of denture biofilm studies have targeted Candida as these fungi are highly adept at adhering to denture acrylic and can induce the infection, denture associated stomatitis. Denture biofilms are, however, ideal for investigating microbial interactions since they are readily accessible, polymicrobial and variable in their microbial composition and can be modelled in vitro. Furthermore, difference in conditioning of the denture surface may also lead to differential species colonisation and biofilm behaviour. Preliminary studies in our School of Dentistry have highlighted the effect that bacterial species may have on denture biofilm composition and behaviour of Candida albicans. We have found that Candida growth can be inhibited in biofilms by Pseudomonas aeruginosa, whilst other bacteria, such as certain streptococcal species can influence the morphologyof C. albicans. The reasons for these effects remain unclear, but could be due to specific associations between species, or a feature of a wider community effect on the biofilm. Project aims The aims of this PhD are therefore to explore the types and mechanism(s) of microbial interactions that occur in biofilms, using denture biofilms as model systems.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified750553Safe and Sound - secure and sustainable Cloud3D servicesClosedVouchersInnovate UKSafe and Sound will enable Hao2.eu to research and develop good practise standards and approaches to deliver secure and sustainable Cloud3D services which proactively anticipate and support the needs of vulnerable groups such as people with autism and learning disabilities.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified288A0B86-D107-4599-8CC3-167C05AF1D49HADWEBUTKNOWN LIMITEDLEAD_PARTICIPANT5000.05000.0NE/H526886/1Doctoral Training Grant (DTG) to provide funding for 3 PhD studentships.ClosedTraining GrantNERCSchool of Life SciencesDoctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedNE/L011956/1Undestanding microbial communities through in situ environmental 'omic data synthesisClosedFellowshipNERCCollege of Science and EngineeringThe purpose of this research is to integrate different sources of 'omics data in environmental science for microbial community analysis. The computational based comparative analysis of DNA sequences may provide information about genome structure, gene function, metabolic and regulatory pathways and how microbial genomes evolve. However, to fully delineate microbial activity and its response to environmental factors, it is necessary to include all levels of gene products, mRNA, protein, metabolites, as well as their interactions. I propose to use large-scale whole genome metagenomic sequencing for assessment of taxonomic and functional diversity of microbial communities. The data generated by metagenomic experiments are both enormous and inherently noisy, containing fragmented DNA sequences representing as many as thousands of microbial species. After using pre-filtering steps, including removal of redundant, low quality sequences, the short DNA sequences are assembled together into longer contigs of overlapping reads, and these contigs may then be scaffolded into full genomes in a bottom-up approach. Having obtained the assembled contigs, the obvious next step is to use publically available databases to annotate the coding regions in these contigs. This will tell us WHAT functionality is available and provide information on WHO is there, the metagenomic sequences are binned, i.e., by associating a particular sequence with an organism. This can be done by either searching for phylogenetic markers or by looking for similar sequences in existing public databases. The end result is the community profile of different samples in terms of organismal abundances within each sample. Whilst metagenomic analysis gives a profile of the microbial community at a specific place or time, and their potential functional, it does not reveal which genes are actually being transcribed. I thus propose to integrate sequencing-based metatranscriptomics in which total RNA (a proxy for gene activity) is extracted from microbial community, converted to cDNA and sequenced without the need for cloning. This will provide information on the regulation and expression profiles of complex communities by enabling quantitative measurements of dynamic expression of RNA molecules and their variation between different states reflecting the genes that are being actively expressed at any given time. However, the story is still far from complete, as we do not have direct evidence of the metabolism within a cell. To give a more complete picture of living organisms, I will integrate metabolomics which will provide unique chemical fingerprints that are a function of specific cellular activity. In particular, the focus will be on identifying habitat-specific endogenous and exogenous metabolites along distinct geochemical conditions. These metabolites will be detected using two-dimensional gas chromatography coupled with mass spectrometry. They will be related to the expression levels from transcriptomes using information on metabolic pathways readily available from annotating metagenomic sequences. In this way we will integrate all three sources of information, mapping the metatranscriptome onto the assembled annotated metagenomes and reconciling the reconstructed metabolic pathways with observations on metabolite concentrations and fluxes. From this we will be able to predict the metabolic function of the entire community not simply who is there.The removal of complex organic contaminants from soils will be one of the major environmental challenges facing the United Kingdom over the coming decades and recommendations based on this proposal will be of use to stakeholders especially, the remediation consultants, industry regulators i.e. SEPA and local councils. Brownfield development is an important part of the societal shift towards sustainability. Many contaminated brownfield sites sit unused for decades because the cost of cleaning them is more than the land would be worth after redevelopment. This research will impact on our ability to achieve sustainable reclaim of environmental capital and will allow adaptive re-usability. The Earth Microbiome Project has generated an enormous collection of data with the intention of producing a global Gene Atlas describing protein space, environmental metabolic models, and characterizing a global environmental parameter space for microbial communities. This global environmental sample database is an ambitious initiative that is community-driven. The tools developed in this fellowship will exploit this vast amount of information to provide useful insights on the Earth's microbiome and to catalogue all the microbes that live on earth. This will be of great benefit to mankind as whole, these microbes are performing vital functions, and to environmental researchers. Methanogenesis is a key process in the carbon cycle, methane is a more potent greenhouse gas than carbon dioxide, therefore understanding its metabolism at a community level is of fundamental importance if we are to incorporate microbial processes into models of climate change. Methane is an important greenhouse gas yet its production could play a part in the transition to a low carbon economy. Water treatment is the fourth most energy intensive sector in the UK and consumes approximately 1% of the UK's electricity. Reducing the energy required to treat wastewater would therefore have major benefits both by reducing costs and carbon dioxide emissions. Anaerobic digestion (AD) reactors have the potential to provide these benefits. They do not require the same energetically costly aeration as aerobic methods and through the action of methanogens produce biogas. Better understanding of methanogenesis could lead to more efficient AD reactors.29F3DF16-3094-4F79-BC69-8D05FB551826Omic sciences & technologies704CCA4C04-0C28-41BE-8869-FA6391A7F005Microbial sciences20F673FD2B-013B-47E5-9E62-03BAB1E7348EEnvironmental engineering10C6A85141-ED79-4266-86E5-F6D25217C97FEnvironmental Genomics40513702B4-7C48-41F2-A1A0-8B4E8BEDCABCAssess/Remediate Contamination10AF3F5E7C-7FB6-4588-9174-6018BA2A231BEnvironmental Microbiology207E61B40B-93E5-4D69-8C89-426ED7E0D2B4Metabolomics / Metabonomics20937A9F23-021A-4604-8979-A28E0E04F825Transcriptomics102430216Real-time prediction of cellular states in 3D lattice light sheet microscopyClosedStudentshipMRCWarwick Medical SchoolProgramme overview: This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project overview: Lattice light sheet microscopy (LLSM) is a new technology to visualise fast cellular processes at the time scale of 1 second, in 3D. LLSM is very low through-put however, limiting its use for studying rare events, such as cell divisions. In close collaboration with industrial partner Intelligent Imaging Innovations Ltd. (3i), suppliers of LLSM, we will develop an integrated imaging pipeline to classify and anticipate physiologically meaningful events during the cell cycle using state of the art machine learning. The main goal is to 1) enable automated control of the image acquisition and increase its throughput, and 2) make it possible to analyse statistically significant numbers of well-defined cellular events and their progression from an early stage, which often go unnoticed by even the most expert human experimenter. Enabling detailed spatio-temporal analysis of the 3D imaging data will help to better understand the timing and control of different stages of cell division and recognise more subtle defects in cell division which can affect development or diseases such as cancer where divisions occur uncontrolled. This is an interdisciplinary project at the interface of cell biology, computer science and engineering, enabling fundamental science to improve human health through world-class biomedical research. Health focus is enabling biological research into genetic risk and disease mechanisms, aiming at new strategies for early diagnosis and treatment. The specific training the student will receive is geared towards quantitative and interdisciplinary skills and understanding of whole organism physiology in addition to that of single cells in the main project. The training in advanced machine learning and computing addresses the demand for team scientists and technology specialists and will help to build new software technologies and imaging instruments that will become available to the biomedical community in the future.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedEP/I016058/1MOLTEN: Mathematics Of Large Technological Evolving NetworksClosedResearch GrantEPSRCMathematics and StatisticsConnections are important. In studying nature, technology, commerce and the social sciences it often makes sense to focus on the pattern of interactions between individual components. Within the UK's Digital Economy activities, for example, large, complex networks arisein energy: connecting power suppliers and users,in telecommunications: connecting mobile phone users,in transport: connecting train stations, airports or ports,in the World Wide Web: connecting web pages,in one-line social networking connecting cyberfriends, in retail trade: connecting sales of different products to the same customer.Improvements in computing power have made it possible to gather, store and analyze large data sets, especially in the areas of fast moving consumer goods (who bought what), telecommunications (who phoned who), mobile devices (who travelled where) , on-line social networks (who Twittered to who) and energy (who switched on when). The interdisciplinary field of Network Science has emerged as a means to understand and quantify these large networks and to extract useful information. By focussing on the underlying connectivity, mathematical techniques can be used to address common questions:Can we discover clusters of strongly connected individuals? This would allow us to break the network down into meaningful subunits.Do the network properties change when links are added or removed? This determines robustness/efficiency to attack/disease/malfunction and stability under evolution.Are some individuals or links especially important? `Hubs' are individuals with high-quality connections (e.g. web pages highly ranked by Google), `short-cuts' are links that join distinct subnetworks and `bottlenecks' are specific links that may become overloaded.Can we develop mathematical models that reproduce the features of a complex network?Given observed output (such as queuing times in a dynamic communication network) can we discover underlying, hidden, connectivity in a complex system?This proposal aims to add value to this important area by addressing an important feature that has fo far received very little attention from the mathematical community. Technological networks vary over time, and this dynamic element has important consequences. For example, if A phones B today and B phones C tomorrow, then a message may pass from A to C, but not from C to A. So there is an immediate lack of symmetry that makes much of the existing theory obsolete. .Moreover, the patterns of connectivity that we see today may be different tomorrow. So there is built-in uncertainty about the future. In this proposal we will develop new mathematical techniques to study the type of dynamically evolving networks that are relevant in the Digital Economy, allowing researchers to discover the important players, quantify the efficiency of a network and predict future behaviour. These ideas offer immediate benefits outside academia, allowing us to tackle questions such as: who are the important broadcasters or receivers of information? who should we target our advertising campaign at? what will the network look like next week or next year? is there any suspicious activity today? which networks users appear to be underage? which customers are likely to change brand loyalty? how quickly will a rumour or virus spread? what would be the effect of changing the way that customers are charged for network usage? Our objectives are to develop to practical, quantitative solutions to these issues by developing a new, underpinning mathematical framework that leads directly to useful computer software. In order to make sure that the results will have immediate benefit, we have put together a team of non-academic experts who use large technological networks in their businesses. These people will provide realistic data sets, pose specific challenges and provide regular feedback and advice throughout the project.Because of its direct involvement with real data sets, and its built-in engagement with specific industrial partners, this project can provide immediate benefit for a number of contributors to and users of the digital economy. The concepts that drive the project revolve around the telecommunications and social networks paradigm: connectivity data produced by mobile device users, from the direct `who-called-who?' patterns to more indirect links, such as, `who-came-geographically-close-to-who?' and connections formed by on-line social interaction. However, the principles apply much more widely to a range of other scenarios where connections may be defined through correlated behaviour, including purchases, web searches and event attendance. In the dynamic network setting of this proposal, there is a clear and immediately implementable benefit for technology providers if we can produce computable measures that summarize the current state of the network. In the longer term, over two to three years, when suitably contextualized, the quantitative measures and inference techniques proposed here would be of interest to a range of e-businesses, health organisations and policy makers who have concerns such as: how quickly could a rumour or disease propagate around this dynamic network? what are the most vulnerable players/connections/times? can we identify players who are engaging in unusual or suspicious behaviour, e.g. in order to target `popular' or 'trendsetting' individuals or to investigate cybercrime? More generally, this type of quantifiable knowledge can improve the way that technological networks, such as `person-to-person' mobile phone, email, SMS or social network activity, `user-to-supplier' smart meter systems and `user-to-product' purchasing data are analysed, managed and expanded, and hence will positively The concrete, transferable skills developed by the Research Assistants on this project will provide them with an excellent grounding from which there are a range of employment opportunities. In particular, familiarity with both computational and statistical tools and an ability to work across disciplines are highly prized by employers, and these are the types of skilled personnel that are needed to boost the UK's high-tech digital service providing work force. At the end of the two year period we have specific plans to extend these methodologies to neruo-imaging (temporal brain activity networks) and smart metering (power usgae nehabior networks), where the proposers can exploit existing links. In addition to publications and conference presentations/posters, there are two formal dissemination routes built into the project. A workshop at the end of each of the two years will bring together academics and industrialists. All proposers have experience of interdisciplinary workshop and conference organisation. Also, a common project website will make computer codes and synthetic data sets available. The project has a Technology Strategy Advisor, Shail Patel, an independent consultant who was previously Director in Unilever R&D of an emerging Platform in Digital Consumers& Markets, which focused on understanding consumer complexity as well as building a new generation of personalised mass-scale consumer services. We also have commitments of time, know-how, software and data from industrial partners, who will (a) ensure that the project aligns with the challenges facing users of technolgoical network science, and (b) provide a fast route to exploitation and benefit for the new tools that are developed.F9D60B1C-1414-49E8-950E-AED6247790F7Mathematical sciences100AD27DF1E-CB87-47B2-892C-C6AA03D1FD47Numerical Analysis508CDDDC47-6DB8-492E-AC56-A075259E49CEStatistics & Appl. Probability50