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

Cell therapy based on regulatory T cells (Treg) transfer has acquired great interest for the treatment of autoimmune diseases, graft rejection or graft versus host disease (GVHD). Until now, this therapy has not rendered definitive clinical results in humans mainly due to the low number and limited quality of differentiated Treg purified from adult peripheral blood. To overcome these limitations, the host group has developed a new technology to produce massive amounts of GMP Treg derived from the thymic tissue (thyTreg), which are being employed in a clinical trial as an autologous cell therapy in transplanted children. However, the massive amount of thyTreg obtained from each thymus make possible to produce hundreds of doses that could be also employed allogenically to treat a range of immune diseases and patients. My experience and acquired skills in immunology will provide the host with the adequate knowledge to develop the allogenic use of thyTreg. The goal of my research will be to investigate the immunogenicity of thyTreg and confirm that its immature phenotype makes possible its “off-the-self” use, and secondly to initiate a clinical trial to evaluate the safety/feasibility of a therapy with allogenic thyTreg in patients with GVHD. The project will establish the basis for the development of allogenic thyTreg cell therapies to suppress the harmful immune response underlying autoimmune diseases, transplant rejection, GvHD, and cytokine release syndrome associated with CAR-T therapy or clinical progress in COVID-19 patients. This innovative project will reinforce my expertise in immune disorders, gaining experience in translational research from the pre-clinical stages to the development of clinical trials and transfer of technology. Being part of this host institution participating in leading projects and international partnerships provides the ideal environment to complete my training and to develop my leadership abilities to become an independent researcher.

Mots clés : treg cells, clinical trials, tolerance induction, cell therapy, graft rejection, autoimmune diseases, covid 19

Participants :
- Fundacion para la investigacion biomedica del hospital gregorio maranon (Espagne) — Coordinator, beneficiary, Autres, subvention : 172932.48 €
Projet MYCO TRAPS (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cell-autonomous immunity is the ability of a host cell to eliminate an invasive infectious agent. Recent work has shown that components of the cytoskeleton have a major role in cell-autonomous immunity and control of bacterial infection. The Mostowy group has shown that some intracellular bacteria, including Shigella flexneri and Mycobacterium marinum, can escape from phagosomes and invade the host cell cytosol where they interact with cytoskeleton components to form actin tails or be entrapped in septin cage-like structures. However, our knowledge of these interactions derives from a limited number of in vitro studies, and has not been fully characterized in vivo during a disease-causing infection. M. marinum, a species closely related to the human pathogen M. tuberculosis, can be applied as a paradigm to understand the cell biology of mycobacterial infection. Zebrafish is naturally susceptible to M. marinum and, as I have shown during my PhD, can be used as an important animal model to gain in-depth information about the innate immune response to bacterial infection. Using state-of-the-art genome editing tools and high resolution microscopy techniques, I will study M. marinum interactions with the cytoskeleton, and investigate the role of these interactions in cell-autonomous immunity. Using M. marinum, my specific objectives are: 1) to identify and characterize host and pathogen determinants affecting autophagy-cytoskeleton interactions, and 2) to investigate the discovered molecules and mechanisms in vivo using the zebrafish model. A more comprehensive understanding of M. marinum-cytoskeleton interactions will have important consequences for enhancing host defense and fighting antimicrobial resistance. This should provide vital clues towards new strategies aimed at combating infectious diseases, and possibly other human diseases that arise from a dysfunctional host response.

Mots clés : autophagy, cell autonomous immunity, cytoskeleton, mycobacterium marinum, septin, zebrafish

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet ISPADMEC (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Cells have the extraordinary ability to regulate their morphology, functions and fate to minimal changes in the extracelullar microenvironment. Through multi-protein, cell-matrix adhesions they are able to recognize and respond not only to the chemical diversity of the extracellular matrix (ECM), but also to its physical and topographical features. Mechanical and structural cues encoded in the ECM have an essential role in healthy tissue function where contractility, spreading and proliferation are intricately regulated by cell-cell and cell-matrix adhesion and tension. Unsurprisingly, abnormal ECM mechanics are directly associated with disease and tissue malformation (atherosclerosis, wound healing and tumor formation). Understanding the mechanisms cells use to sense and transduce mechanical signals, as well as the contribution of key players in the process is a pressing, unmet challenge. To achieve this goal, I here propose the development of an in vitro strategy that allows precise regulation of both biochemical and mechanical parameters in order to isolate their contribution on fundamental endothelial cell (EC) functions. The proposed work will exploit advances in materials science and nanotechnology to modulate with high precision the presentation of highly selective integrin ligands at the nanometer and micrometer length scales, on substrates with tunable viscoelasticity and mechanics. The anticipated effects of integrin engagement and substrate mechanics on ECs will shed light on how the microenvironment affects their proliferation, activation and directional migration, and help correlate these finding with pathological scenarios where blood vessel mechanics and EC integrin expression are deregulated. In summary, the proposed interdisciplinary approach will contribute both advanced tools to study cells in vitro and crucial answers for specific questions relating to EC biology.

Mots clés : mecanotransduction, extracellular matrix, integrins, hydrogels, micro, nanopatterning

Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 171460.8 €
Projet TuRCreg (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Cells regulate the nucleation of microtubule polymerization locally and temporally, which is translated into accurate organization of the microtubule cytoskeleton, crucial for proper cell function. It is well established that the major microtubule nucleator in animal cells, the γ-tubulin ring complex (γTuRC), is central for such regulation and its implication in disease is clear. However, for more than 20 years, nobody was able to dissect the molecular mechanism of microtubule nucleation by γTuRC, a current big question in the microtubule area of research. Now, this project will make this challenge achievable by taking advantage of very recent technological advancements in the microtubule field. Aiming to dissect the molecular mechanism of γTuRC-mediated nucleation, the work here proposed will pioneer the reconstitution of physiological microtubule nucleation by γTuRC, using an original combination of biochemistry, single molecule microscopy and structural biology approaches. This will contribute to the progress in understanding microtubule organization and dynamics in cells, and will open new perspectives to explore further the molecular mechanisms behind the diseases associated to γTuRC and γTuRC-associated proteins (e.g. neurological conditions and cancer). This proposal will not just accomplish the current challenges in the cytoskeletal field as will serve as the basis to understand and possibly treat such diseases, which are included on the European Union research priorities regarding the Horizon 2020 program. The creative and innovative nature of this project will also place myself, the host lab and the Institute where the project will be developed, and the EU in the forefront of research in the microtubule cytoskeletal field, contributing to my main goal in becoming a leader in molecular and cell biology of the cytoskeleton, in Europe.

Mots clés : cytoskeleton, single molecule microscopy, in vitro reconstitution, turc mediated microtubule nucleation, cell egg extracts

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

Cells sense extracellular signals via their surface localized transmembrane receptor kinases. Although long regarded as a conduit for cell surface receptor degradation or recycling, the endosomal system is also an essential site for signal transduction. Say endosomes are the logistics platforms for receptors, activated receptors accumulate in endosomes, and certain signaling components are exclusively localized to endosomes. Receptors can continue to transmit signals from endosomes that are different from those that arise from the plasma membrane, resulting in distinct physiological responses. In mammals, endosomal signaling was demonstrated for many receptor families including receptor tyrosine kinases, G‐protein‐coupled receptors and toll‐like receptors. Unlike mammals, the mechanisms of endosomal signaling in plants are unknown. Recent study of the immune receptor PEPR1 that perceives the endogenous peptide Pep1, showed that endocytosis is required for mitogen-activated protein kinase (MAPK) activation after elicitation with Pep1. However, because MAPK activation occurs faster than the endocytosis of the main receptor it raised the question if endocytosis of so far unknown signaling components is required for Pep1-elicited immune responses. In ENDOLOGISTIC, I aim to identify those components. To reach this goal, I will perform proteomics and phosphoproteomics analyses on isolated endosomes after elicitation with Pep1. This will enabled me to map and to correlate endosomal-specific phosphorylation with changes in subcellular protein distribution. Furthermore, I will employ the proximity labelling method to identify components of both the PEPR1 signaling complex and endosomal or autophagy machinery. In ENDOLOGISTIC I will combine my expertise in immunity with state -of- the -art proteomics, live cell imaging and genome-editing techniques available at the host institute to further advance our understanding of how endocytosis controls immunity in plants.

Mots clés : arabidopsis, clathrin coated vesicles, endosomal signaling, phosphoproteomics, pepr1 receptor

Participants :
- Vlaams Instituut voor Biotechnologie (Belgique) — Coordinator, beneficiary, Recherche, subvention : 178320.0 €
Projet MicroProtLip (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Cellular function and malfunction depends crucially on the interactions of proteins and other cellular components, specifically with lipid membranes. Such interactions are a key to the compartmentalization of a wide range of cellular mechanisms into discrete organelles, allowing to maintain homeostasis. In spite of implications to life sciences and drug discovery our current understanding of protein–lipid interactions is limited. This is primarily due to the challenges imposed by existing methods for determining the fundamental interactions of a wide range of proteins and lipid bilayers due to the high level of heterogeneity of the formed complexes. Recent advances in the development of microfluidic techniques for characterisation of biomolecular complexes together with sensitive optical detection methods open new possibilities for fundamental studies of protein–lipid interactions. The main objective of the proposed project is the development of a transformative microfluidic platforms dedicated for the study of interactions of lipid membranes with protein molecules. Experienced Researcher aims at the implementation of microfluidic technologies: micro free flow electrophoresis and nano deterministic lateral displacement, for the parallel development of two types of platforms. The development of the platform will be highlighted by addressing exemplary fundamental questions in molecular biology of interest that concern a wide range of aspects of mechanism of protein–lipid interaction. The realization of the objectives will be based on close collaboration between academic and non-academic sectors, in pursue to bridge the gap between fundamental and applied research. This action will set up a tight collaboration between the University of Cambridge (UCAM) and Fluidic Analytics Limited (FAL) who have pioneered the use of commercial microfluidic platforms for efficient characterization of biomolecular interactions.

Mots clés : microfluidics, microfluidic diffusional sizing, micro free flow electrophoresis, microfabrication, protein lipid interactions, lipid vesicles, neurodegenerative diseases

Participants :
- Fluidic analytics limited (Royaume-Uni) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 212933.76 €
Projet PRO-CLEAR (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Cellular homeostasis and survival critically depend on the ability to remove misfolded and damaged proteins. In cells, proteins are continuously exposed to reactive metabolites which introduce modifications such as oxidation, carbonylation, glycation or carbamylation. Such non-enzymatic post-translational modifications (nePTM) can irreversibly block critical interaction surfaces or reactive sites and thus pose a constant threat to proteome integrity. In line with this view, levels of nePTM are increased in diseased and aged tissues. In contrast, nePTM-bearing proteins are selectively degraded in healthy cells, suggesting the existence of a so far unknown pathway that recognizes and eliminates nePTM-bearing proteins. In this project, I will study the impact of nePTMs on protein turnover and explore the underlying molecular mechanisms. More specifically, I plan to (I) establish a reporter assay to monitor the degradation of proteins displaying individual amino acid modifications in human cells. This will allow to test effects of common nePTMs and to identify the precise chemical adducts that induce protein clearance. Aim (II) is to uncover the cellular machinery that mediates nePTM-triggered protein degradation. To this end, I will perform a genome-wide CRISPR screen for genes required to eliminate a fluorescent model substrate. Aim (III) of the project is to understand the mechanisms underlying the recognition and clearance of nePTMs. I will therefore characterize one newly identified mediator of nePTM-clearance in detail and test its ability to bind, degrade or modify nePTM-bearing proteins and will study the impact of its knockout on the turnover of endogenous proteins. Together these experiments promise to uncover a novel pathway for the quality control of chemically damaged proteins which will form the basis for understanding its role in physiology and human disease.

Mots clés : cellular homeostasis, protein quality control, carbamylation, carbonylation, glycation, oxidation, crispr screening, non enzymatic post translational modifications

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191149.44 €
Projet Lipid and Polarity (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cellular polarity is a universal feature of eukaryotic biology. Failure to control cell orientation has dramatic consequences on embryogenesis and diseases including cancer. The establishment of cellular polarity often entails the asymmetric distribution of plasma membrane (PM) lipids signaling proteins and vesicle trafficking. The function of Rho proteins in cell polarity has been demonstrated from mammalian cells to yeast. The small GTPase Cdc42 is a pivotal regulator of polarity establishment and maintenance. A central feature of Cdc42 function is its ability to interact with membrane. In budding yeast, Cdc42 localizes asymmetrically at the PM, at the pole of the cell, along with the scaffold protein Bem1 and the Cdc42 activating GEF Cdc24. The asymmetric distribution of lipids in the internal leaflet of the membrane play a crucial role in the regulation of Cdc42 activity and localization, though the mechanisms are not completely understood. The organization of lipids in the PM influences the spatial distribution and activity of key signaling proteins as Ras family proteins. Ras forms nanoclusters in cell membranes that are essential for signaling and Phosphatidylserine lipids have been shown to play a role in the assembly of K-Ras nanoclusters in mammalian cells. In this work, we will study Cdc42, Cdc24 and Bem1 dynamics in the membrane and particularly at the polar cap. To address these challenging questions, we will be using lipid mutants (cho1∆, psd1∆ psd2∆…) in Saccharomyces cerevisiae. We are tracking Cdc42 polarity module components in these mutants at the single molecule level by super-resolution imaging in live cells. This system enables the quantification of the diffusion and clustering of individual molecules at the PM, and the contribution that the lipid environment imparts in vivo. In addition, using this powerful system, we will analyze the nano-organization of different phospholipids involved in signaling (PS, PE, P(I4,5)P2, PI4P).

Mots clés : lipids, polarity, single molecule tracking, super reolution, palm, saccharomyces cerevisiae

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet NanoHeal (Horizon 2020, appel à projets 2014)
Action : Doctoral Networks
Panel : Physics
Statut du projet : CLOSED

Cement production for the construction industry contributes up to 5% of anthropogenic CO2 emissions. Developing more environmentally friendly concrete requires the assessment of strength for a diverse range of new cement materials. Similar issues arise during the development of biocompatible cements for medical applications. Properties of naturally cemented materials of organic origin are of key importance in the oil industry, with carbonate reservoirs prone to creep, particularly during the injection of CO2 for enhanced oil recovery or permanent storage. However, despite the importance of cement materials to our infrastructure, health and environment, we still lack the fundamental basis for understanding the strength of cemented aggregates. Granular pastes and sediments transform to strong solids through reactions at nano-confined mineral interfaces, where nucleation and growth at the adjacent solid surfaces are affected in a manner not yet understood. There is a need for improved concepts, theories and models. NanoHeal targets this issue by bringing six industrial and six academic groups together in a European Training Network (ETN), in an emerging interdisciplinary field spanning from basic sciences to the corresponding engineering disciplines. NanoHeal will deliver an outstanding environment for training and career development of young researchers. The aims of NanoHeal are to: • develop innovative probes and models for nanoscale processes that open novel perspectives in design and control of organo-mineral materials. • measure and improve the strength and durability of 1) new man-made cemented materials like “green concrete”, speciality cements in construction and oil and gas recovery, and biocompatible implants and 2) natural sedimentary rocks inside reservoirs and as construction materials • educate young interdisciplinary researchers at the interface between fundamental science and European industry.

Mots clés : cement, carbonate rock, deformation, strength, organic, mineral composite

Participants :
- Technion – Israel Institute of Technology (Israël) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 520601.04 €
- University of Erlangen-Nuremberg (Allemagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 249216.48 €
- University of Oslo (Norvège) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 858825.72 €
- NORCE Norwegian Research Centre (Norvège) — Partner, beneficiary, Recherche, subvention : 0.0 €
- Université Claude Bernard - Lyon 1 (France) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 788626.8 €
- Imperial College London (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 819863.64 €
- University of Copenhagen (Danemark) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 580163.76 €
Projet CENTROMD (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Centrosomes are organelles composed of a pair of centrioles surrounded by a pericentriolar matrix (PCM) that perform a variety of key functions in the animal cell. Centrosomes duplicate precisely once during S-phase of the cell cycle; in G2-phase the two centrosomes move to opposite locations around the nucleus and expand their PCM to nucleate vast quantities of microtubules for mitotic spindle formation. Dysfunctions in the centrosome cycle have been associated with a wide range of pathologies and, in particular, centrosome amplification, an aberrant increase in centrosome numbers, is a hallmark of most human cancers. Centrosomes are complex machines composed of hundreds of proteins, however significant efforts over the past decades have identified the key elements which are essential for centriole and centrosome biogenesis. We can now address the molecular mechanisms that mediate interactions between key players and how these contribute to regulate the number and size of these organelles during the cell cycle. Elucidating these mechanisms is of great interest to cell biology and cancer research. This research proposal aims to investigate aspects of centriole and centrosome biogenesis using Drosophila melanogaster as an animal model. The main objectives are: 1), to reconstitute initial steps of centriole assembly using a hybrid in vivo/in vitro approach, where I will study the molecular dynamics of the interaction between key centriolar proteins Asl and Plk4, using functionalised microspheres as a scaffold and 2), to analyse the dynamic behaviour of single molecules of key centrosomal proteins Cnn and Spd-2 as they move throughout the PCM during expansion, using super-resolution microscopy techniques. We are confident that these studies will provide novel insights into the design principles and inner workings of these important organelles.

Mots clés : centriole and centrosome biology, single molecule localization microscopy, super resolution microscopy, in vitro reconstitution of biological systems

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €