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

Globally, suicide is the second leading cause of death among young people aged 15-29. Many European countries have seen a sustained increase in youth suicide rates in recent years. Despite the deployment of comprehensive and multilevel suicide prevention strategies, we still do not know which suicide prevention interventions, for which groups of young people, for how long, and with what intensity could generate the most significant reductions in youth suicide rates. Therefore, we cannot efficiently and effectively inform decision-making in youth suicide prevention policy, planning and implementation. Current methodological approaches (meta-analyses, regression models) for synthesizing and operationalising research evidence used to inform suicide prevention strategies have limited adequacy and accuracy because they do not: respond to real-time suicide data; account for the interrelationship, interdependence and nonlinearity of suicide risk factors as they operate across multiple levels (e.g. individual, social); consider the influence of factors such as healthcare constraints (access, capacity). SEYMOUR offers a novel paradigm for guiding the efficient and effective deployment of national and global youth suicide prevention strategies through the use of system dynamics modelling (SDM). SEYMOUR will develop and evaluate a novel SDM that will demonstrate which suicide prevention interventions could generate the most significant reductions in suicide rates among young people aged 12-25. This will include an implementation blueprint to facilitate the transferability, internationalisation and adoption of the SDM as a decision-making tool in youth suicide prevention policy and practice in Europe and globally. The conceptualisation, formulation, testing of the SDM; and, development of an implementation blueprint will take place during Years 1 and 2 at UoM. The validation of SDM in the UK and adaptation of the implementation strategy (WP4) will take place during Year 3.

Mots clés : suicide prevention, system dynamics modelling, young people, implementation, social policy

Participants :
- University of Melbourne (Australie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 295940.16 €
Projet INTERGLP1 (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Glucagon-like peptide-1 is a key regulator of insulin and blood glucose release. The cognate receptor, the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR is a major drug target for type 2 diabetes. Agonist-induced internalization is a major regulatory mechanism for GPCR signalling. Interestingly, GLP-1R internalizes via a mechanism that is distinct from the canonical beta-arrestin mediated pathway. However, the details of the exact mechanism is largely conflicting and poorly understood for GPCRs in general. The present project aims to develop genetic and pharmacological tool box to dissecting the intracellular pathways leading to GLP-1R internalisation. To do this, 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 utilise theses cell lines to dissect pathways leading to GLP-1R internalization and endosomal signalling. To understand the role of bias in the complex signalling profile of GPCR, I will also develop conformationally selective nanobodies using the yeast surface display platform. 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 : gpcr, glp 1r, crispr, cas9 genome editing, internalization, endosomal signalling, nanobody

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet F4TGLUT (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Glutamate is the primary activating neurotransmitter in the brain. It modulates synaptic plasticity of neurons, which underlies memory formation. However, it also plays a fundamental role in pathological processes, such as those related to Alzheimer’s disease. This essential role and future development of therapeutic agents urge the development of a highly-sensitive analytical method for determining glutamate levels at a cellular level. In this project I will create a miniaturized, in vitro system that will allow this. To develop it, my expertise in microfluidics and pharmacy will be supplemented by the host’s extensive experience with cell analysis and nanoelectrodes. When glutamate-type neurons in the brain are innervated, glutamate release into the synapse between adjacent neurons occurs. This triggers chemical signal transmission. Nanoelectrodes are uniquely equipped to monitor this neurotransmitter release with unprecedented spatiotemporal resolution. The combination with microfluidics will allow control of fluids and experiments at the nanoliter scale. Furthermore, through precisely fabricated microstructures, guidance of cell growth and precise placement of the nanoelectrodes in the device will be achieved. Glutamate modulates synaptic plasticity, a phenomenon understood to underlie memory formation. Furthermore, dietary compounds and drugs can influence glutamate neurotransmission. The proposed system enables selective exposure of individual neurons cultured in the microfluidic device to such compounds. Using the integrated nanoelectrodes, direct monitoring of their effects on chemical signaling between cells will be possible. The results will significantly contribute to our understanding of glutamate neurotransmission, and how drugs and diet can influence it. Additionally, the system combines cell culture, selective exposure and analyses at the cellular level using sensors and imaging, making it an ideal platform for future drug development research.

Mots clés : glutamate, neurons, nanoelectrodes, microfluidics, zinc, lipids, memory

Participants :
- University of Gothenburg (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191852.16 €
Projet GLYCOMIMIC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Glycosciences study the structural and functional roles of carbohydrates in biology and have an increasing impact on many areas of our economy (health, food, natural resources). Carbohydrate Active enZymes (CAZymes), which catalyse the assembly (Glycosyl transferases, GTs) and breakdown (Glycosidases, GHs) of glycosidic linkage in carbohydrates, are essential to life, being involved in key cell functions. Their pharmacological modulation by means of selective CAZymes’ inhibitors can have multiple applications (e.g. antiviral TamifluTM, antidiabetic GlysetTM, molecular chaperone GalafoldTM). However, the design of inhibitors endowed of high selectivity is challenging, representing the major obstacle in discovering new potent and safe therapeutic agents targeting CAZymes. In this context, GLYCOMIMIC offers an innovative approach based on superacid chemistry to gain insights into CAZymes’ transition states (TS) and to help the design of specific inhibitors, paving the way for short-term impact on drug discovery! Superacid chemistry is only mastered by very few research groups in the world and is a European specificity of the Institute of Chemistry of Poitiers (IC2MP - UMR CNRS 7285 – France) and will be applied for the first time to glycosciences. With Univ. Barcelona (world leader in computer simulation of biological processes at atomic-electronic detail) acting as secondment, GLYCOMIMIC blends multidisciplinary states of the art research training in carbohydrate chemistry, superacids, low-temperature NMR analysis, DFT calculations, QM/MM dynamic simulation of enzymes and enzyme inhibition studies. It will provide a prolific fellow with an internationally competitive training, with the aim of advancing the career of an autonomous scientist in the EU and the next generation of multidisciplinary researchers in (bio)pharmaceutical sciences.

Mots clés : superacids

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 184707.84 €
Projet Au-MLC (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Gold catalysis has gathered increasing attention from the synthetic community during the last decades, due to the remarkable ability of Au centres to promote chemical transformations. Typically, gold catalysis is based on its peculiar properties as a Lewis acid, that make it very well suited for the activation of unsaturated bonds. On the other hand, the use of gold in more sophisticated processes, such as cooperative catalysis, is at its pioneering stage, and only few examples of these strategies are currently known. Metal-Ligand Cooperation strategies (MLC) are an emerging tool in homogeneous catalysis, based on the interplay between the metal centre and the non-innocent (bifunctional) ligand. This synergy vastly enhances the performances of known transformations, and even enables new sets of reactivities. MLC has been applied to many metal centres, often with spectacular results; Au-MLC strategies, however, are unknown to date. This project focuses on the development of a family of novel Au(III) complexes bearing Brønsted basic, non-innocent pincer ligands characteristics. Their fundamental study will be performed, assessing their Lewis acidity (especially in the Pearson HSAB scale), their Brønsted basicity, and their stoichiometric interaction with X–H bonds. Based on these results, their use as bifunctional Lewis-acid catalysts will be explored for the electrophilic activation of alkynes, carbonyl compounds, and alcohols. The design and development of sequential reactions involving the bifunctional gold catalysts obtained in the context of this project will be the ultimate, most ambitious goal of this action.

Mots clés : metal ligand cooperation, bifunctional catalysis, gold catalysis

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 184707.84 €
Projet CombLimit (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : CLOSED

Graph limit theory is a new and important field, motivated by large real-life networks such as the internet, the nervous system, traffic networks, social networks, interaction graphs of proteins, etc. Sparse graph limit theory is a direction partially inspired by these applications. This is a new and intensively studied field, and one of the two main topics of the research proposed. Local algorithms or constant-time distributed algorithms is an important tool for sparse graph limit theory, and this is in the focus of the proposed research. It is also useful to understand stochastic processes and phase transitions in large networks, and it is strongly related to ergodic theory. The applicant very recently demonstrated through some examples that the tools of limit theory can be very useful in solving combinatorial problems as well. This observation opened the door for plenty of new applications, which are also in the focus of the proposed research. With the proposed CombLimit initiative the applicant would complement the research agenda of the Rényi Institute, and he would also be an important link connecting pure mathematics with its applications in computer science, economics, physics and biology. Upon completion of the CombLimit MSCA program, the applicant will have a good basis for successfully applying a tenured/permanent position at Rényi Institute.

Mots clés : combinatorics, graph theory, stochastic methods, local algorithms, limit theory, game theory

Participants :
- Hungarian Academy of Sciences (Hongrie) — Coordinator, beneficiary, Recherche, subvention : 134239.2 €
Projet GreenAnt (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Greenbeard genes are selfish genetic elements (SGEs) that favor their own transmission by increasing the fitness of other carrying individuals. Such a phenotype, can only occur if a gene or a group of tightly linked genes produce (1) a conspicuous phenotype, (2) the ability to recognize this phenotype, allowing the bearer individual to discriminate carriers from non-carriers and (3) a nepotistic behavior in favor of carriers. These extraordinary SGEs can have profound evolutionary consequences on genomes and social behavior. The first identified Greenbeard haplotype was in the fire ant Solenopsis invicta. In this species, the Social b (Sb) supergene, an 11 Mb non-recombining region is associated with a Greenbeard effect. Discriminating on cuticular chemical profiles, carrier ant workers spread the Sb supergene by killing non-bearer queens. In this project I aim to identify the genetic basis of the queen-discrimination ability of Greenbeard-carrier ant workers. I will first compare the molecular evolution of the Sb supergene with the non-driving homologous haplotype over multiple bearer and outgroup species. Then I will compare patterns of expression of Sb supergene genes in antennae and brains between workers. Lastly, I will functionally validate candidate genes by genetically altering their sequence in workers. I will assay the impact of the knock out on the Greenbeard effect by testing the queen-discrimination ability of transformed workers. Using this combination of techniques and analyses, the GreenAnt project will tackle the molecular basis and evolution of Greenbeard genes in metazoan organisms.

Mots clés : social evolution in ants, selfish genetic elements, greenbeard genes

Participants :
- University of Lausanne (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €
Projet EDAPOL (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Group polarization is a collective phenomenon that typically occurs when an initial tendency of individual group members toward a given direction is enhanced following group discussion. For example, a group of members of the same party will get more convinced of their opinion after an internal debate. The most convincing explanation provided for polarization by social psychologists is based on Persuasive Arguments Theory. The explanation holds that individuals become more convinced of their view when they hear novel and persuasive arguments in favor of their position. Therefore group discussion causes an individual to shift in a given direction to the extent that the discussion exposes that individual to persuasive arguments favoring that direction. However, the exact mechanisms by which this process unfolds are still unclear. The main aim of the EDAPOL project is to unveil the deep structure of the process of information flow and opinion change that generates polarization in a group. To this end, two main tools are combined: argumentation frameworks (AF) – mostly used in artificial intelligence – and logics of information change (LIC) – developed by logicians. The combination of such analytical tools allows to model the knowledge base of an individual (AF), its modification by the successive steps of information exchange (LIC) and, subsequently, to analyze all critical points where polarization can arise in a debate. Understanding polarization on a rigorous basis meets an important societal challenge in the era of social media. Indeed, virtual online discussion witnesses a more pronounced tendency for groups to polarize towards opposite directions than face to face discussions, with a detrimental impact on the associated life of our society. The project will widen Dr. Proietti skillset and provide an important added value towards Dr. Proietti's professional aim of becoming a distinguished researcher in the area of logical research applied to social sciences.

Mots clés : epistemic actions, abstract argumentation, group polarization, dynamic epistemic logic, argumentation frameworks

Participants :
- University of Amsterdam (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165598.8 €
Projet eWAD (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Growing evidence suggests that unbalanced Wnt signalling contributes to early stages of Alzheimer´s Disease (AD). mRNA levels of the Wnt antagonist Dikkoff1 (Dkk1) are increased in AD brains and by Amyloid-ß (Aß) in vitro. Importantly, suppression of Dkk1 activity protects synapses from Aß. Genome-Wide Association Studies also provide evidence for deficient Wnt signalling in AD. The host laboratory has recently demonstrated that Dkk1 induced expression in the adult hippocampus leads to synapse loss and cognitive impairment; defects that can be restored by Wnt signalling reactivation. My preliminary results demonstrate that mRNA levels of several Wnt components (Wnts, their receptors and antagonists) are affected in a transgenic mouse model of familial AD, suggesting a general downregulation in Wnt signalling. These findings raise two main questions. Is aberrant expression of Wnt components an early event in AD? What mechanisms lead to aberrant Wnt component expression in AD? Given that Wnt signalling is crucial for synapse maintenance, and that my preliminary results suggest a coordinated downregulation of the Wnt pathway in AD, I will examine the role of DNA methylation at Wnt component genes in AD and how this affects synapse integrity. The potential role of DNA methylation is supported by: i) AD patients and mouse models exhibit global DNA hypomethylation and gene-specific DNA hypermethylation, ii) DNA methylation at promoters leads to gene repression, but intragenic methylation can enhance transcription, iii) Wnt components contain CpG islands at their promoters and/or intragenic regions, and iv) some Wnt components are regulated by DNA methylation in cancer. My work will define the role of epigenetic regulation of Wnt components under physiological conditions and determine the relevance of unbalanced Wnt signalling in AD. This research project could also identify new biomarkers and novel therapeutic targets for the treatment of early AD stages.

Mots clés : alzheimer s disease, amyloid, wnt signalling, wnt components  wnts, frizzled receptors and wnt antagonists, epigenetic regulation  dna methylation

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet Flat_Leaf (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Growing flat leaves is crucial for plant success, since it directly affects light interception and photosynthesis. This process is tightly regulated by endogenous signals revealing a strongly genetically defined developmental program, but is also modulated by the light environment. As shown using null mutants, both blue light receptors phototropins (phot) and red/far-red light receptor phytochromeB (phyB) affect leaf flattening, and it was recently found that plants lacking PKS3, a protein involved in phot signaling, suffer severe flattening defects. The main objective of this project is thus to determine how light signals interact with endogenous cues to control development of a flat leaf. First, I will perform an exhaustive temporal and spatial characterization of the phot and phyB-mediated light control of leaf development applying various light treatments and complementing phot1phot2, phyB and pks3 with tissue-specific promoters. Next, I will apply the latest microscopy techniques to determine the expression pattern of leaf development markers under various light conditions and in photoreceptor mutant backgrounds. Also, given the major role of auxin in leaf development, and the various ways in which phot and phyB control it, I will study auxin abundance, transport and sensitivity at the tissue and cellular level. Finally, I expect to identify new components of phot signaling evaluating the interactome of PKS3 through IP-MS. Thereby I expect to determine how a conserved developmental program and photosensory cues crosstalk to control leaf flattening.

Mots clés : leaf flattening  blue and red light  phototropins  phytochrome  dorsiventrality  adaxial, abaxial polarity

Participants :
- University of Lausanne (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175419.6 €
Projet WIDEA (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Guided waves are recognized as one of the most promising techniques for Structural Health Monitoring (SHM), as they provide reliable, long-range and highly sensitive damage inspection capabilities. Progress in this field would be impactful to EU transportation, aerospace and offshore industries, where safety is crucial given the potential human, economic or environmental consequences of failures. Despite some encouraging applications to lightweight components, the implementation of SHM strategies in advanced structures remains challenging. Indeed, in order to combine high stiffness-to-weight ratio with vibro-acoustic requirements these structures frequently involve composites, dissipative materials or periodic patterns to produce desirable response within targeted bandwidths. These new lightweight designs also produce more complex propagative behaviours, such as mode conversions or Bragg resonances, which result in highly scattering waves and increased noise-to-signal ratios. To overcome these limitations, new studies must exploit the remarkable scattering properties of these waves. In this research, a numerical framework will be developed to predict and explore the physics of guided waves’ interaction with commonly encountered structural damages. These interactions, described by frequency-dependent ‘diffusion properties’ will allow the creation of an innovative feature-based characterization technique exploiting the wave conversion phenomenon. The outcomes of this project will result in a new type of wave-based SHM system able to cover the upcoming generation of lightweight components. Undertaking this research with two high-ranking representatives of their fields, along with formal training and mentoring activities will enhance the researcher’s academic profile and scientific experience. It will also provide him with an outstanding content expertise in wave-based methods, structural health monitoring and modelling of lightweight composites.

Mots clés : lightweight structures, structural health monitoring, wave, finite element, composite, vibro acoustics, periodic structures

Participants :
- KU Leuven (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160800.0 €