Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet HepEDOT (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Cell therapy has emerged as a promising therapeutic strategy for cardiac repair, showing modest cardiomyocyte protection and infarct size reduction. It is under debate whether these outcomes are due to the implanted cells or their paracrine factors, as cells are scarce within a few weeks post-implantation. Regardless, this is still not sufficient to promote cardiac remuscularization and reverse medium to severe myocardium injury and fibrosis. Improved cell retention has been achieved with a substantial bulk of implanted cells, but highly associated to graft-induced arrhythmia, representing a significant challenge for clinical translation. The present study seeks to promote cardiac remuscularization after infarct, by improving the retention of cardiac cells and their paracrine factors without causing graft-induced arrhythmia. To do so, a conductive, self-doping and biodegradable oligoEDOT-heparin biomaterial will be synthesized and studied on in vitro and in vivo cardiac infarct models. The conductive EDOT oligomer moiety is envisaged to act as an electrical sink to shield the cardiac tissue from mismatched electromechanical impulses, while heparin will facilitate cardiac cell support and loading of regenerative factors, besides its recently documented doping capacity. The results of this fellowship are expected to overcome low cell retention and graft-induced arrhythmia, two of the biggest obstacles for translation in cardiac cell therapy, but also contribute with new insights regarding conductivity in materials and biological systems, to multiple fields of materials chemistry, medicine and bioelectronics. The world-class academic environment, collaborations and combined interdisciplinary expertise in biomaterials and cardiovascular sciences make the proposed fellowship activities ideally placed for enhancing my career prospects and consolidating my host and Europe in a leading position for translational research.

Mots clés : conductive biomaterial, cardiac cells, paracrine factors, cardiac infarct, immunomodulation, arrhythmia

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet ModEvoCell (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Cell types with distinct functions coexist and cooperate within a single animal, eventually contributing to the endless forms most beautiful that define the animal kingdom. These cell types are complex phenotypes defined by multiple traits—ontogeny, morphology, regulatory and transcriptional states, etc.—that are ultimately encoded by the same genome, and are thus subject to the evolutionary process. Therefore, to study the diversity of cell types from an evolutionary perspective we need to first understand the patterns of conservation and divergence in the various traits that determine cell phenotypes. Among these traits, gene regulation is uniquely amenable to be systematically catalogued and compared across species, and it is an ideal candidates to support a model of cell type evolution. Here I propose to investigate the evolution of animal cell types in a multi-species comparative framework. I hypothesise that, by characterising the cell type and transcriptomic programmes of various species along a spectrum of phylogenetic divergence times, I will be able to infer a data-driven model to quantify the influence of regulatory divergence on cell type evolution. To that end, I will build cell type diversity atlases of six placozoan species and resolve their transcriptomic states at single-cell resolution using scRNA-seq, genome-wide profiling of regulatory regions (ATAC-seq and regulatory motif discovery), and gene regulatory network modelling. Placozoans are a uniquely well-suited model for this research: they have a strongly conserved yet profoundly simple bauplan, composed of few cell types, that can be fully resolve at the whole-organism level using single-cell transcriptomics. This taxon-rich survey across multiple species and cell types will allow me to address the fundamental question of how cell types emerge and diversify, and it will provide a theoretical basis to understand how regulatory divergence ultimately results in phenotypic innovation.


Participants :
- Centre for Genomic Regulation (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet ECtomics (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cells with stem cell potential, this is with the ability to self-renew and generate specialised progeny, exist in the adult mammalian spinal cord. Previous studies localised this potential within the ependymal cell (EC) population. However, ECs are rather heterogeneous based on their morphological features and the expression of a handful of neural stem cell markers. In this interdisciplinary research proposal, I aim to uncover the cellular and molecular heterogeneity of ECs at the level of individual cells. I propose to take advantage of cutting-edge single-cell RNA-sequencing technology to obtain the transcriptomes of individual ECs from the spinal cord of adult mice. Using advanced computational methods, I will establish EC types and states and use pseudotemporal ordering to elucidate potential lineage relationships among ECs. I will then validate these findings in the tissue context, using high-resolution confocal microscopy. This first comprehensive characterisation of spinal cord ECs will provide novel and fundamental insights into how ECs possess and maintain their unique self-renewing properties. In the future, this will facilitate realisation of the potential of spinal cord stem cells for therapeutic purposes.

Mots clés : neural stem cells, spinal cord, single cell rna sequencing, quiescence

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

Cellular diversity in the nervous system determines the variety of circuits that set the framework for brain function. These different types of neurons emerge during pre- and post-natal development through the regulation of gene networks by two archetypical processes: cell-intrinsic processes, which are independent of environmental conditions, and cell-extrinsic processes, which are triggered by environmental signals. A continuum of interactions between intrinsic and extrinsic processes underlie cellular states. However, their respective contribution to neuronal identity has been difficult to untangle because neurons are highly interconnected and heterogeneous cell-types with distinct and dynamic sensitivities to environmental signals. Here, using the mouse neocortex as a model system, I will investigate how cell-intrinsic and cell-extrinsic processes interact to define neuronal identities using Patch-seq assessment of neuronal molecular identity following transplantation across cortical areas. Neuronal “plasticity” will be assessed by transplantation, which corresponds to the artificial altering of the environmental factors. Data comparison between transplanted neurons and controls will identify the candidate of “core genes” which regulate the environment-dependent plasticity of neuronal differentiation. Finally, I will manipulate these candidate genes and analyze their effect on final neuronal identity to validate their causal relationship. Altogether, this study will contribute to revealing the plasticity of neuronal identity across cortical areas and to addressing environment-dependent molecular mechanisms controlling the plasticity. In the long term, this may contribute to a better understanding of neurodevelopmental and psychiatric disorders, in which cell-intrinsic and extrinsic factors interact to produce the disease.

Mots clés : self organization, neural differentiation

Participants :
- University of Geneva (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €
Projet SingleCellAI (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cellular identity is controlled by cell type specific expression of transcription factors (TFs), and it is reflected in the cell’s epigenetic landscape maintained by epigenetic regulator proteins (ERs). Functional dissection of cellular identity has focused mainly on a small number of lineage-defining master regulators, yet there is increasing evidence that multiple TFs and ERs work together to establish and retain the vast number of different cell types and cell states in the human body. For a more quantitative understanding of cellular identity, and of the complexities of its regulation, I propose to develop a machine-learning approach for in silico prediction of TF/ER cocktails that can transdifferentiate any human cell type into any other cell type, thus defining an operational rulebook of cellular transdifferentiation. To this end, I will train a machine-learning model called generative adversarial networks (GANs) on large-scale CRISPR single-cell sequencing (CROP-seq) datasets generated in the host lab. Exploiting unique features of the deep-learning generative approach, the resulting model will be able to generalize the learned genetic perturbations across cell types in silico. I will experimentally validate several of these predicted TF/ER transdifferentiation cocktails in the context of the human hematopoietic system. Importantly, the proposed approach is hypothesis-free and data-driven, exploiting recent advances in machine learning to infer fundamental aspects of the regulation of cellular identity from high-throughput functional CRISPR single-cell sequencing data.


Participants :
- Austrian Academy of Sciences (Autriche) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 186167.04 €
Projet MicroMAM (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cellular protein homeostasis (proteostasis) is central to health and disease status. It depends on complex regulatory networks of two major interconnected proteolytic degradation pathways: the ubiquitin-proteasome (UPS) and autophagy systems. Here we will investigate whether a novel proteostasis pathway, called the Intracellular Pathogen Response (IPR), recently identified in the model system Caenorhabditis elegans, is also active in mammalian cells. In C. elegans the IPR is upregulated during infection by Microsporidia, a highly successful group of obligate intracellular parasites that infect a broad range of invertebrates and mammals, including humans. Very little is currently known about mammalian intracellular responses to Microsporidia infections. The objective of the project is to dissect the mammalian proteostasis response to Microsporidia infections and compare it to the IPR from C. elegans. To accomplish this a multidisciplinary approach combining genetics, cell biology and proteomics will be applied to Microsporidia-mammalian models developed in the host lab. The proposal involves a promising French researcher with a background in invertebrate parasitology and host responses to infection, moving to a host laboratory in Newcastle, UK, noted for excellent training of young researchers, and for its research on Microsporidia molecular cell biology. Training in analysing Microsporidia infection dynamics in mammalian cells will be supported by host training in dissecting cellular proteostasis pathways to synergistically complement the skills of the researcher in invertebrate parasitology. The project will equip the researcher with strong expertise in molecular cell biology from a comparative perspective. It will also deliver the first detailed insights into the mammalian UPS/autophagy response to Microsporidia infection, with general implications for understanding mammalian proteostasis in health and disease.

Mots clés : autophagy, ubiquitylation, cell biology, virus, proteomics

Participants :
- Newcastle University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet RespViRALI (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cellular respiratory complexes play a central role in the production of ATP, the universal energy source of life. Defects in their activity are linked to neurodegenerative diseases in humans and antibiotics resistance in bacteria. Despite their capital importance, the assembly mechanisms of respiratory complexes remain highly unexplored. This research project aims to investigate how the assembly of the major bacterial respiratory Complex I is assisted by a multi protein system involved in enterobacterial stress response. The host team recently solved the structures of two components of this system with cryo-electron microscopy (cryoEM) and X-ray crystallography, and showed that they form a huge cage-like assembly reminiscent of the GroEL-ES chaperone. Importantly, the latest scientific literature reported physical interactions between this macromolecular assembly and specific subunits of E. coli respiratory complexes. To elucidate the functional role of this enigmatic machine in the assembly of Complex I, I will employ a highly integrated approach situated at the front line of molecular structural biology. A wide range of biophysical methods will be used to dissect the affinity and kinetics of individual interactions between components of this multi protein system and subunits of Complex I. I will examine the overall architecture of the formed complexes with negative stain electron microscopy and small-angle X-Ray/Neutron scattering, while atomic resolution insights of the complexes will be provided by high resolution single particle cryoEM and X-ray crystallography. The structures and functional insights obtained in the proposed project will improve our general understanding of coordination between protein folding and assembly of respiratory complexes, and bring novel insights into their implication in antibiotics resistance and pathways of bacterial stress responses, which are crucial to developing strategies for controlling infection.

Mots clés : respiratory complexes, chaperone, macromolecular machine, protein assembly, x ray crystallography, electron microscopy, bacteria, antibiotics resistance

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet WoodTiMe (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

Centuries-long societal relations uniting Euro-African territories have modulated the forest history. Grazing and use of wood as an essential material have led to overexploitation of woodlands with lagged environmental problems like deforestation, severe flooding, encroaching deserts and declining ecosystems productivity. These human-environment interactions are well presented in the centre of these linkages, the Strait of Gibraltar, where the legacy of such history has survived in millennial forests and timber in archaeological sites or historical buildings. The project's objectives are: 1) to characterize historical exploitation of forests and its relation with the past forest dynamics using dendrochronology in ancient Andalusian and Moroccan forests 2) to explore the potential of deriving post-medieval ecological and societal changes from archaeological and historical timber 3) to apply emerging proxies (wood traits, DNA, chemical composition) to develop novel tools for identification of timber origin that may explain past human-environment interactions. To achieve these objectives, the project will be implemented in three stages: 1) Collection of ancient trees samples in Baetic mountains and Moroccan Rif and Atlas to analyse the forest history and unlock the wooden archive containing the key for understanding the historical exploitation of resources. Tree-growth chronologies and wood traits will be estimated by wood scanning and measurement of tree-ring widths. 2) The legacy of forest history and wood trade between trans-Mediterranean continents will be analysed through multi-century ring series preserved in archaeological and post-medieval historical wood material. Old buildings will be explored to analyse wood origin in relation to the magnitude of historical use of forests. 3) Application of a battery of novel techniques (blue intensity, wood anatomy, elemental composition and stable isotopes) for developing a new timber provenancing tool – dendroscapes.

Mots clés : human environment interactions, dendrochronology, wood sciences, timber, dendroarchaeology, past climate, forest disturbances, relict forest, mediterranean forest, timber dna, dendroprovenancing

Participants :
- Universidad Pablo de Olavide (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet ChaConGen (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Chagas disease (CD) is a parasitic, systemic and chronic disease caused by the protozoan Trypanosoma cruzi. Approximately 30% of chronically infected people develop cardiac, digestive, neurological or mixed alterations. CD affects 7 million people worldwide, mainly in endemic areas of 21 continental Latin American countries, where T. cruzi is mainly a vector-borne disease. In non-endemic regions, a major role is played by congenital (mother-to-fetus) transmission, leading CD to become an emerging disease in Europe and other non-endemic regions. It is increasingly clear that more efforts are needed at the basic research level to improve our understanding of the molecular and clinical aspects of this route of transmission. Understanding the genetic bases of the interaction between the host and the parasite could shed light into the molecular mechanisms behind congenital transmission. In this project, we aim to use state-of-the-art genomic techniques to understand the relationship between T. cruzi genotype and the host genotype in congenital transmission of CD. Identifying the factors governing this matter will not only help to better understand the mechanisms behind the diseases, but it could also help to target the group of infected pregnant women at higher risk of transmission. We will examine the parasite and the host genotypes in blood samples from infected pregnant women transmitting and not transmitting the infection. We will assess parasite diversity by developing a new strategy for T. cruzi genetic typing based on the MinION, a portable long-read DNA sequencer. For the genotyping of the host, we will use genome-wide SNP arrays. We will use multivariate analysis for determining putative relationships between host and parasite genotypes and congenital transmission of CD. This project will provide the first attempt at determining genetic causes of congenital CD considering both, host and parasite genotypes by applying the state-of-the-art genomic techniques.

Mots clés : chagas disease, congenital transmission, pregnancy, newborn, t  cruzi, host parasite genotype, typification, snp array, nanopore sequencing

Participants :
- CERCA Institution (Espagne) — Coordinator, beneficiary, Recherche, subvention : 224496.96 €
- Consejo Nacional de Investigaciones Científicas y Técnicas (Argentine) — Partner, organization partner, Recherche, subvention : 0.0 €
Projet Phil-Threats (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Challenging the traditional understanding of colonial rule in the early modern period, this project proposes a new perspective on how colonial systems of dominance operated, offering an innovative view on mechanisms of governance. Applying interdisciplinary methods, it emphasizes political communication as key element in the creation and consolidation of a system of power. Focussing on the colonial Philippines as a transcontinental cultural contact zone, this project investigates the concept of external threats as a fundamental element of political communication. Thereby, it advances simultaneously along two analytic lines, investigating (1) forms of threat representation, and (2) their effects. Based on the sociological theory that external threats can foster the cohesion of a group, the hypothesis of this project is that specific representations of “enemies” contributed to the success of the Spanish colonial system for a long period (1565-1898), by strengthening the unity within the Spanish system and helping to overcome internal problems. To prove this effect, the project combines aspects of (1) system theory (N. Luhmann) and (2) the method of dispositif analysis (M. Foucault), which until now have only been applied separately. Based on system theory models, a concept of threat-communication is defined as a first analytic step for the investigation. It is completed with the concept of a dispositif of threat, which includes not only discourses in texts, but also visual forms of representation, objects, and performative acts – giving the project a pronounced interdisciplinary feature. Overall, the project will contribute to a better understanding of the power structures of the Spanish colonial systems in particular and mechanisms of political communication in general. In addition, it will enhance the skills of the Experienced Researcher (ER), enabling him to become a leading expert in his field and to find an independent position in research.

Mots clés : philippines, early modern history, spanish empire, political communication, global history

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 170121.6 €