Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet INTERGLU (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The metabotropic glutamate receptor 5 (mGlu5) is part of the large family of G protein-coupled receptors (GPCRs) that are the target of 30-40% of marketed drugs. mGlu5 is a key regulator of synaptic plasticity in the brain and a major drug target for a wide range of diseases, such as Fragile X syndrome. Agonist-induced internalization is a major regulatory mechanism for GPCR signalling. Interestingly, mGlu5 internalizes via a mechanism that is distinct from the canonical beta-arrestin mediated pathway. However, the details of this alternative mechanism are largely unknown for mGlu5 and poorly understood for GPCRs in general. The present project has the dual aim (1) to dissect the intracellular pathways leading to mGlu5 receptor internalization and its functional implications and (2) to develop a genetic and pharmacological toolbox to study beta-arrestin independent internalization. I will generate a series of HEK293 cells where key proteins involved in a range of GPCR internalization pathways have been systematically removed by CRISPR/Cas9 genome editing. These cell lines will complement the already existing G protein alpha subunit and beta-arrestin knockout HEK293 cell lines to generate a highly efficient toolbox to study pathways and mechanisms involved in GPCR signalling, internalization and regulation. In the present project, I will employ theses cell lines to dissect pathways leading to mGlu5 internalization. To enable future studies in cells with native mGlu5 receptor expression, pharmacological tool compounds/peptides targeting key proteins identified will be developed using the genome edited HEK293 cells. This will provide essential information about the regulation of this important drug target and beta-arrestin independent internalization. Importantly, we will make the cell lines and pharmacological tool compounds available to the scientific community enabling similar studies on a much wider range of GPCRs.

Mots clés : g protein coupled receptors  gpcrs, metabotropic glutamate receptor 5  mglu5, crispr, cas9 genome editing, endocytosis, internalization, trafficking

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €
Projet MArylAND (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The microbial community in the human intestine is crucial to the health and nutrition of the host. Loss of the fragile balance within this complex ecosystem is involved in numerous pathologies, including inflammatory bowel disease (IBD). The incidence of IBD is increasing and affects individuals in challenging years of their lives, with immunosuppressive treatments that are not always effective. IBD results from a combination of genetic predisposition, alteration of the gut microbiota, and environmental influences. Thus, deciphering the host-bacteria crosstalk will improve our understanding of IBD and enable new preventive and therapeutic strategies. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, codes for a protein involved in the response to fungi and bacteria. Sokol and colleagues showed that Card9-/- mice have an increased susceptibility to colitis, due to an altered gut microbiota that is not able to metabolise tryptophan into aryl hydrocarbon receptor (AhR) ligands. In humans, comparable mechanisms seem to be involved, as microbiota of IBD patients exhibit impaired production of AhR ligands, which mirrors the Card9-/- genotype. We aim to decipher the mechanisms involved in the modulation of the microbiota and its metabolic activity by Card9. For this purpose, we will take advantage of a strong collaborative environment and cutting-edge techniques, including gnotobiotic animals, cre-lox technology, transcriptomics, metabolomics and systems biology. Specifically, we plan to identify (i) new pathways and cell types involved in the modulation of the microbiota and its metabolic activity, and (ii) microorganisms and metabolites activating AhR receptors in the gut. This highly innovative and integrative project will allow me to expand my conceptual and technical knowledge of the gut-microbiota interface, acquire new key skills and strengthen my scientific network.

Mots clés : inflammatory bowel diseases, mucosal immunology, microbiota, commensal bacteria, dysbiosis, tryptophan metabolism, aryl hydrocarbon receptor  ahr  ligands, systems biology, innate immunity

Participants :
- Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet ONCOPHAGY (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The microenvironment of most solid tumors tends to be significantly more acidic than healthy tissue. Inadequate perfusion, oxygen limitation and cell metabolic changes, are key causative factors for this situation. The acidic pH induces a number of specific genetic, transcriptional and metabolic effects in tumor cells. These are required for survival under increased H+-stress. Evidence is now mounting that these effects also play a major role in tumor progression, invasiveness and the development of multi-resistance to therapy. Two pivotal adaptations related to maintaining intracellular pH homeostasis in an acidic environment, have recently received significant attention: (1) the presence of chronic autophagy in tumors and (2) the overexpression of carbonic anhydrases (CAs), mainly CA IX and CA XII. This project will biopharmaceutically optimize a novel class of specific autophagy inhibitors that target Atg4B. The specific goal of this part of the project is to obtain orally bioavailable and metabolically stable compounds that are fit for in vivo applications. The relevance of these compounds is clear, given the unmet demand for reliable, specific inhibitors in the domain of autophagy. At the same time, the project will evaluate the potential for therapy development of the compounds in the framework of cancer. Finally, the proposal will explore whether a further increase of anti-tumor efficiency can be obtained by combining Atg4B- and CA-inhibitor pharmacophores in a single compound.

Mots clés : autophagy, atg4b inhibitors, dual  atg4b carbonic anhydrase  inhibitors, oncology

Participants :
- University of Antwerp (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160800.0 €
Projet MIRCOMB (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

The mid-infrared (MIR) spectral window is a gold mine for molecular spectroscopy and chemical/biological sensing, where the absorption strengths of molecular transitions are 10 to 1000 times greater than those in the visible or near-infrared (NIR), offering the potential to identify the presence of substances with extremely high sensitivity and selectivity, and is thus a powerful tool for scientific, commercial, industrial, and military applications. Future developments of MIR spectroscopy require the creation of robust, coherent sources that can operate with high precision, over a broad bandwidth, and over a wide range of environmental conditions. Quantum cascaded laser (QCL) is one of the most successful realization of MIR laser sources. While QCLs offer excellent spectral coverage in MIR, their use in spectroscopy is primarily restricted to continuous-wave (CW) techniques, since they are difficult to mode-locking. In this proposal, we provide a technology to transfer such powerful CW MIR laser light into coherent and broadband optical frequency combs with high precision, which is an ideal MIR source to spectroscopy. The technology is based on chip-scaled silicon-based micro-resonators which has shown successful frequency comb generations in near-infrared with mode spacing in micro-wave range, octave-spanning bandwidth and compact form. The formation of temporal dissipative solitons in such resonators further leads to a fully coherent frequency comb with access to ultrashort femtosecond pulses. In this two-year project, we aim to implement chip-based MIR frequency combs, including finalizing a reliable MIR photonics platform that could provide high-quality and high-finesse micro-resonators, generating MIR soliton-based fully coherent frequency combs that have broad bandwidth under dispersion engineering on resonator waveguides, and accomplishing a dual-comb based MIR spectroscopy system that could provide high-speed, high-sensitive and broadband detections.

Mots clés : optical frequency combs, mid infrared laser physics, micro resonators

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175419.6 €
Projet RNAhello (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The mimicking of cellular communication pathways and genetic information transfer in synthetic systems is an important target for researchers. These artificial cell systems have the potential to increase understanding of biological and cellular processes, while also having potential applications in healthcare technologies. This project will involve the investigation of exciting new stimuli responsive and highly tuneable hierarchical polymer protocells, and their application in RNA-based communication. Previous generations of polymer protocells have been shown to allow diffusion based communication with small molecules and naked DNA strands – the project will expand upon this by investigating polymersomes as mRNA shuttles between distinct protocell populations. This exosome inspired system will allow the typically unstable mRNA molecules to be protected from degradation in the external medium, thus opening the door to much more lifelike systems, and possible therapeutic applications. The proposed research project is strongly multidisciplinary, and involves a combination of polymer chemistry, nanomaterials engineering, cell biology, and imaging techniques. RNAhello includes both the transfer of knowledge to the host institution and the training of the candidate in new advanced techniques. Results have the potential to increase understanding of biological mechanisms in relation to the complex hurdle of the nucleic acid based transfer, whilst also providing innovative platform material for treatment of disease. Additional project goals include: engaging with the non-scientific public through outreach methods; gaining of further commercial training for potential exploitation of research; presentation of research results at international conferences; and the preparation of additional funding proposals.

Mots clés : systems chemistry, artificial cells, coacervates, mrna

Participants :
- Eindhoven University of Technology (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175572.48 €
Projet IDEAA (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

The modern world witnesses an explosion of digital content; for example, the European Data Portal, managed by the Publications Office of the EU, provides more than 10.000 datasets produced by EU institutions and bodies and harvests more than 750.000 datasets of Public Sector Information. This leads to opportunities for EU citizens to witness, analyze and monitor the functioning of their representative institutions, and tremendous challenges in making sense of the data, in particular by interpreting them in the context of specific needs. A citizen interested in an issue such as “undergraduate education” has no means to easily follow EU institution activity on it and compare it with activity and regulations in one's country. A lot of public information is available, however, acquiring a comprehensive picture and understanding the consequences, implications and correlations of this issue with respect to a bigger (European) arena is very difficult. IDEAA (Issue-Driven European Arena Analytics) will allow citizens to easily explore the trove of publicly available data. Its features are: (i) supply users with succinct and meaningful knowledge with respect to their issue of interest; (ii) allow users to interact with the provided knowledge to refine their information need and advance understanding; (iii) suggest interesting or unexpected aspects in the data and (iv) support the comparison of knowledge discovered from different data sources. The research is to be focused on RDF data; the EU Data Portal alone exposes more than 20.000 RDF datasets. However, despite their abundance and continuous growth, consolidated approaches for RDF analytics are still lacking. The research will be concretized in a web-based prototype encompassing theoretical results and providing the four described features. To the best of our knowledge this will be a pioneering tool, dedicated to general public, for easily analyzing RDF data with the aim of building a viewpoint on a specific issue.

Mots clés : rdf analytics, insights extraction, succinct meaningful knowledge, data exploration

Participants :
- Institut national de recherche en sciences et technologies du numérique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet embryonic rosettes (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The mouse embryo is an excellent model for human development. Its preimplantation stages of development in vitro have been extensively studied. Now similar approaches can be applied to implantation stages, previously hidden from view in the uterus. It was recently revealed that formation of a rosette structure by pluripotent epiblast cells can be recapitulated by ES cells cultured in extracellular matrix proteins. I will determine the extent to which such rosettes can undertake autonomous development or if they require flanking extraembryonic tissues. I will characterise the patterns of the normal development of these tissues from the point of implantation to the time of gastrulation. I will determine the extent to which explants of extraembryonic tissues can influence the development of rosettes of epiblast cells. Altogether, these experiments will expand our knowledge of embryonic development and how to manipulate the developmental potential of pluripotent cells.

Mots clés : mouse embryo, development, implantation, embryonic stem cells

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet ClauSeInTEL (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

The nature of the relationship between a verb and its grammatical dependents is an ancient question in linguistics, tracing back to Aristotelian notions of the subject-predicate relation. A major debate in current theoretical linguistics is how to model this, and the standard view (that the relevant information is stored as part of the grammatical specification of the verb) has been challenged by the development of a new idea: that both the verb and its noun-dependents are embedded inside syntactic hierarchies of fundamentally grammatical elements (socalled “functional categories” encoding notions such as tense, aspect, definiteness and numerosity) and that it is the interaction between the functional category structures that embed the verb and the noun that is responsible for establishing the dependency. This viewpoint has allowed a new and empirically successful understanding of the relationship between a verb and its dependents, capturing how definiteness and grammatical number interact with aspectual categories across different languages. However, this new approach has never been applied to the other major grammatical dependency that verbs set up: clausal complementation. That is, the parallel relation between a verb and its clausal, as opposed to nominal, dependents. This project investigates, using interdisciplinary methods, whether these new theoretical ideas can be applied to this empirical domain, comparing two languages (Greek and English) whose clausal syntax is quite different. The objective is to both test the theoretical model in a new empirical area, leading to new findings about how clausal embedding works syntactically, and to determine how best to develop and extend the model to domains that it was not designed for. The action requires extended training in experimental methods and design (both behavioural and neurolinguistic), statistical analysis, development of systematic theoretical models, as well as interaction with a non-academic partner

Mots clés : syntactic theory, experimental linguistics, greek language, english language

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet SPOTplasma (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

The need and importance of newborn screening (NBS) is a reality in most of the western countries. NBS helps with the detection and prevention of important health issues during neonates first days of life, avoiding growth or mental retardation or even potential deaths. Even when each individual disorder has a low incidence into the population, their cumulative occurrence is relatively high, around 1 in 1,500 to 1 in 5,000. Most of the NBS programs in western countries are well established but there is a constant need for new methodologies that can tackle more efficient, cheaper, faster, and simpler ways to analyze different disorders. SPOTplasma will help to address innovative methodologies for NBS. Firstly, the project will tackle the idea of unaltered NBS sample analysis with no sample or minimal preparation steps considered as a kind of “Holy grail” for precious samples. And secondly, during SPOTplasma a platform based on ion mobility spectrometry (IMS) will be investigated as an alternative for newborn screening in developing countries, barely implemented due to the lack of well-equipped infrastructures in their public system along with the high costs associated with MS instrumentation. In conclusion, SPOTplasma will address dried blood spot (DBS) analysis by developing analytical tools that can speed up the screening process or cheapen the analysis. Novel methodologies based on a flexible Tube Micro Plasma (FμTP) coupled to mass spectrometry (MS) and stand-alone IMS are proposed for DBS analysis not only for NBS but also in the pharmacological industry.

Mots clés : newborn screening, dried blood spots

Participants :
- University of Jaén (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet HARM (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

The need to minimize the amount and foster the safe treatment of waste, and thereby reduce the risk of contamination; emphasises the importance of promoting technologies which are environmentally sound with products suitable for re-use/recycling. This project establishes a laboratory experimental study to determine the performance of clay mixed with construction and biomass plant waste (fine recycled aggregates, FRA, and/or biomass bottom ashes, BBA) as materials for the enhanced attenuation of contaminants in landfill leachate. The aim is to (1) evaluate the contaminant attenuation capacity of these mixtures for different conditions, (2) develop design guidelines to construct barriers for waste containment systems and similar applications, and (3) interpret their performance using numerical modelling tools. Column experiments where landfill leachate is passed through different waste:clay mixtures will be run in a state-of-the-art centrifuge facility which simulates realistic times, pressures and temperatures of landfill field conditions. The geochemistry of the column pore water and material residues after permeation with leachate will be examined to deduce the processes responsible for pollutant removal and retention. After permeation with landfill leachate, the effects of exposure of these barriers to an aggressive acid environment, rainfall infiltration and rising water table will be studied. The concept will be applicable for barrier design at other waste disposal facilities. The results will provide a novel and timely improvement which addresses the problem of managing the vast amounts of industrial residues such as FRA and BBA. Instead of disposal these will be re-used/recycled as an additive in host clay for building contaminant barriers, thus also conserving natural resources (clay and other man-made barrier materials). It will also provide an effective and more environmentally sustainable basis to control landfill pollution risks.

Mots clés : waste to resource, barriers, leachate, landfill, attenuation, long term attenuation performance, design, clay, aggregates, ashes, environmental management, reversibility, recycling

Participants :
- University of Sheffield (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet SpTheoryGraphLim (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : CLOSED

The need to understand the behavior of real-life networks made it necessary to work out non-standard graph theoretic tools capable of dealing with a large number of interacting nodes. New mathematical areas emerged, such as graph convergence or parallel algorithms. The proposal suggests the study of the spectral aspects of these areas. The proposed research is built around two core problems that grew out of and are natural continuations of Harangi's previous work in spectral graph theory at the University of Toronto. One is a spectral version of the so-called soficity problem, a major open question in the area of Benjamini-Schramm convergence. The other is an ambitious conjecture of Harangi and Virag concerning eigenvectors of random regular graphs, stating that these eigenvectors converge to Gaussian wave functions. In the past few years the Renyi Institute has become the European center for studying graph convergence with several experts of the field working there as well as many talented and motivated graduate students and postdoctoral fellows. Being a member of this research group will allow Harangi to collaborate with researchers from various different mathematical disciplines. The proposed research topic is at the meeting point of these areas. The host's expertise in groups and graph limits will complement Harangi's analytic skills. The proposed fellowship would give Harangi an excellent oppurtinity to work with some of the top researchers in his field, to acquire the necessary tools to crack the exciting research problems proposed and to make the optimal next step in his career.

Mots clés : large networks, graph theory, graph convergence, spectrum, spectral measure, local algorithms, factor of iid processes, random graphs, unimodular random networks, soficity

Participants :
- Hungarian Academy of Sciences (Hongrie) — Coordinator, beneficiary, Recherche, subvention : 134239.2 €