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

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bi-directional mechanical exchange is crucial for many cell functions, is remains poorly understood, mostly since the majority of ECMs, both natural and synthetic, are difficult to control or lack biological relevance. A new synthetic polyisocyanide (PIC) gel is the first material that is an excellent mimic of the ECM (porous network architecture and nonlinear mechanics, including stiffening) and can independently tailor mechanical and biological properties. The gel is developed at Radboud University Nijmegen, where I finished my PhD. In this action, I want to study how forces from the cell or the ECM change the mechanical properties of the matrix and, more importantly, how this change affects biological functions. To this end, I will combine the unique, highly tunable PIC gels as synthetic ECM and study the matrix and cell behavior using advanced microscopic imaging techniques and spatial proteomics. Through PIC functionalization, I can tailor the size and number of focal adhesions (FAs), i.e. the protein complexes that link cells to the ECM. The forces generated by cells will be quantified both on cellular and single FA level by traction force microscope (TFM) and molecular tension sensor-based FRET. In addition, proteomic analysis will be performed to evaluate the effect of gels with different mechanical properties in the proteome. These results will have a high impact for understanding how cells interact with matrix through forces. Beyond my knowledge in biomaterials, I will gain new expertise in super-resolution microscope and mechanobiology at KU Leuven. This project highly matches the mission of the Marie Skłodowska-Curie Individual Fellowships to achieve two-way knowledge transfer and to promote my future career prospects.

Mots clés : mechanobiology, cellular force, biomimetic hydrogels

Participants :
- KU Leuven (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178320.0 €
Projet SizerSingleCell (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cells have strict control over their size to ensure proper cell physiology. They also have ways to correct for deviations, referred to as cell-size homeostasis, leading to a very narrow distribution in cell size at division. Although some of the genes involved in this process have been identified, the underlying molecular mechanism has remained elusive. One possibility is that the cell can “sense” its size through a protein whose concentrations are related to cell-size ‒ known as the sizer model. However, this would not completely explain the fact that diploid cells are approximately twice the size of haploids, suggesting that ploidy also plays a role ‒ something that has not garnered a lot of attention in the field. Live-cell fluorescence microscopy is well-suited to address these issues because we can directly visualize the dynamics and localization patterns of sizers, along with cell-size, and quantify these characteristics. I propose to develop a live single-cell fluorescence microscopy approach using a microfluidics device that allows mother cell lineages to be tracked across multiple generations, for use with haploid and diploid strains of the unicellular eukaryotic organism, Schizosaccharomyces pombe. This will allow me to measure protein levels of sizer candidates and their localization, along with cell length, across single lineages. This information could reveal long-term dynamics and correlations between sizer candidates and cell-size, and provide insight into the molecular mechanisms governing cell-size homeostasis and the role that ploidy plays in governing cell-size control within eukaryotes.

Mots clés : cell cycle, microfluidics, size sensing

Participants :
- The Francis Crick Institute (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 212933.76 €
Projet MechanoGenetic (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cells in our bodies constantly experience mechanical forces from their microenvironment. When cells sense a critical threshold of elevated tension, they hold tight together and allow tissues to function healthily as a group. In certain diseases, however, our cells lose their mechanosensing and adhesive properties and, as a result they get dissociated, as in the case of muscular dystrophies. Integrin-based adhesions to the extracellular matrix (ECM) are emerging as key networks of mechanotransmission. This proposal aims to discover how mechanical forces modulate cell-matrix adhesion at the myotendinous junctions in the developing Drosophila embryo, combining biophysical, molecular and genetic approaches. To achieve this goal, I propose to implement two complementary specific objectives: First, I will identify and quantify the relationship between forces and adhesion strength in mutants affecting either integrin-ECM binding or muscle contractility by utilizing in vivo laser ablation and magnetic tweezers. Second, I will examine whether and how IPP complex -a core module of the integrin adhesome- alters the molecular forces transmitted across Talin, which is a major mechanosensor at integrin junctions, utilizing suitable FRET-based biosensors. Collectively, this interdisciplinary research will provide a novel mechanical framework of how cells integrate forces and maintain tissue integrity in the living organism. Given the striking similarities in the molecular organisation of the myotendinous junctions between fly and human, the outcome of this work will provide a deeper understanding of how we can better combat dystrophic diseases.

Mots clés : mechanotransduction, integrins, cell adhesion, cytoskeleton, flim, fret, muscle, drosophila, myopathies, magnetic tweezers

Participants :
- Biomedical Research Foundation of the Academy of Athens (Grèce) — Coordinator, beneficiary, Recherche, subvention : 153085.44 €
Projet UNICAT (Horizon 2020, appel à projets 2014)
Action : Staff Exchanges
Panel : Information Science and Engineering
Statut du projet : CLOSED

Central venous catheters (CVCs) play a critical role in healthcare and few medical devices are more important and widespread in modern medicine. Catheter-related bloodstream infection (CRBSI) is the most common life-threatening complication of CVCs. Reducing the risk of CRBSI among patients would save costs, reduce length of stay and improve mortality and morbidity. The major challenge of UNICAT is thus to develop a new CVC solution to prevent infection and thrombosis. The project partners will introduce a whole new way of thinking by introducing a disruptive approach which is more than just a coating of devices. A new material will, for the first time, combine ultra-biocompatibility with chemical resistance and desired mechanical properties, to effectively prevent adverse host response, inflammation and infection. A major problem in biomaterials science is that bioresistant materials are inevitably also chemically inert and hence highly difficult to manipulate by traditional wet chemistry. If manipulation (e.g. coating) is achieved, the solution is often unstable and fragile. UNICAT will address this problem by combining two materials using a novel method based on super critical CO2-chemistry. It will result in a hybrid material which is stably formed and combines the best properties of two or more materials. The success criterion is to exceed performance of coatings by producing the first fully biocompatible material to be used as sole robust bulk material of vascular access lines. UNICAT is an international and inter-sector collaborative project comprising R&D activities and secondments between the SME BioModics (BM), the University of Minho (UMinho), the Bar-Ilan University (BIU) and the Simula Research Laboratory (Simula). The consortium has identified the RISE programme as a suitable vehicle for overcoming the identified major challenges and for bridging the knowledge gap, while helping to overcome the financial, technological and intersectoral barriers.

Mots clés : hybrid materials, nano particles, medical devices, antibiotics

Participants :
- Bar-Ilan University (Israël) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 18000.0 €
- University of Minho (Portugal) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 130500.0 €
- Biomodics aps (Danemark) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 49500.0 €
- Simula Research Laboratory (Norvège) — Partner, beneficiary, Recherche, subvention : 9000.0 €
Projet ANTIQUITATES (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Cesare Pastorino will carry out this two-year Marie Curie Global Fellowship at Princeton University (USA) and the University of Venice Ca’ Foscari (Italy), with the supervision of Anthony Grafton (Princeton) and Marco Sgarbi (Venice). The overarching aim of the ANTIQUITATES project is to investigate the quantitative empirical practices of the early modern historical disciplines. Pastorino will analyze the case of antiquarian architecture in the Republic of Venice during the sixteenth century. He will consider a group of groundbreaking architects from Veneto, including Andrea Palladio (1508-1580) and Vincenzo Scamozzi (1548-1616), and their patronage networks. The activities of these architects moved seamlessly from texts to objects and back, merging the study of classical authors with archeological reconstructions, surveying, and practical mathematics. In their antiquarian analyses, these figures blended historical and quantitative empirical knowledge. Historiography usually associates quantitative empirical methods with the early modern growth of the natural sciences. Analyzing the patronage networks of antiquarian architecture in the Republic of Venice during the sixteenth century, this project will open a very different and innovative perspective: it will show how the humanistic and antiquarian study of the past included established practices of measurement and quantification. In sum, Cesare Pastorino will lay the foundations for a new and cutting-edge area of historical research on the role of quantification, measurement, and testing in the historical studies of antiquity in early modern Europe. This new research and the skills acquired during the fellowship period will impact his career very significantly. They will expand his current area of expertise, create new academic collaborations and provide him with the training required to achieve a permanent academic position and establish a research group on this topic.

Mots clés : renaissance, antiquarianism, early modern science, empirical knowledge, classical tradition, antiquities, practical mathematics, material culture, measurement and quantification, patronage, venice

Participants :
- Ca' Foscari University of Venice (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 180369.6 €
- Princeton University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet Evo-Devo-Whales (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Cetaceans (baleen whales and toothed whales) are a distinctive group of mammals that has evolved unique adaptations to live in water. Their impressive fossil record traces their evolution from their terrestrial ancestors (Artiodactyla), to the present aquatic forms. All living cetaceans have flippers instead of limbs, possess a blowhole at the top of the head instead of an anteriorly-positioned nose. They have also developed a characteristic head shape connected to their feeding mode: while baleen whales have lost their teeth and feed using keratinous plates called baleen, toothed whales have evolved the ability to locate their prey using sound waves (echolocation). Changes in prenatal development (ontogeny) played a major role in allowing these animals to evolve the skull adaptions they currently display related to their peculiar traits. Though, little information is available on their development, limiting our understanding of the role of ontogeny in the evolution of modern cetaceans. This project aims to apply 3-dimensional (3D) imaging and cutting-edge geometric morphometric (GM) and phylogenetic methods to quantify the ontogeny of the skull in a diverse sample of cetaceans and terrestrial artiodactyls in order to reconstruct how development has shaped the evolution and diversification of this unique group of mammals. This project will produce high-quality 3D datasets that will be shared in on-line repositories, making rare fetal specimens of toothed and baleen whales accessible for further research and for outreach initiatives. The project will benefit from the expertise in GM methods of a world-renowned researcher and her team, and the vast collection of specimens available at the host institution. Through this fellowship, the researcher will be reintegrated in the European scientific community and master key skills to then start her independent career. She will learn new methodologies, while strengthening transferrable professional skills.

Mots clés : evo devo, evolution, development, cetacea, mammals, geometric morphometrics, phylogenetic methods, diversification, environment, ecology

Participants :
- Natural History Museum (Royaume-Uni) — Coordinator, beneficiary, Organismes publics (hors enseignement & recherche), subvention : 212933.76 €
Projet GABARPET (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Changes in GABA receptors are known hallmarks for numerous neurological diseases including schizophrenia which is a severe psychiatric disorder that has a profound effect on both the individuals affected and society. The diagnosis of schizophrenia is complex because of the loss of high specific biomarkers. Research papers have suggested that the differential expression of GABAA receptors in the brain is associated with this mental disease. The current evidence on GABAergic abnormalities in schizophrenia is mostly based on postmortem studies and, in this sense, in vivo measurements of GABAA receptor subunits can reveal additional insights. This project will develop Positron Emission Tomography (PET) probes which could unveil quantitative information about GABAA receptor expression in schizophrenia patients. However, the lack of imaging tracers with high affinity and specificity do not shed a clear light on the diagnosis in a traditional PET setting. In this sense, the immune-positron emission tomography (immunoPET) is a non-invasive technology based in antibody imaging which reveals a specific and sensitive molecular characterization of the cell surface phenotype in vivo. Nevertheless, its success in neuroimage is limited because of intact antibodies cannot penetrate the Brain Blood Barrier (BBB) in healthy conditions. However, GABARPET will tap into a small recombinant bispecific antibody construct targeting the GABAA receptors as well as the transferrin receptor because it is able to readily transmigrate across the BBB in vivo after peripheral injection. This project wants to develop di-single-chain variable fragment (di-scFv) directed to α1 and α2 subunits of GABAA receptors. Then, they will be labeled with conventional radionuclides produced by cyclotron as 18F and 89Zr. ImmunoPET probes will be used in wild-type mice, GABAA receptor knockout mice and different kind of rodent models of schizophrenia.

Mots clés : gabaa receptors, schizophrenia, immunopet, blood brain barrier, electrophysiology, pharmacology, antibody engineering, molecular biology, radiochemistry, single chain variable fragment

Participants :
- University of Turku (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 304021.44 €
Projet XYMOF (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Chemical separation technologies consume 15% of the global energy. Separation of xylene, a common chemical produced on an enormous scale, is one of the most difficult cases, due to very similar physical properties of xylene isomers. This project will address this challenge by identifying an adsorptive material with superior selectivity towards the desired isomer, compared to the current state-of-the-art adsorbents. A very selective material, used as a membrane or in the adsorption unit, would make a step-change in the xylene separation technologies and lead to significant energy savings. To achieve this overall objective, I put together a novel computational strategy by combining molecular simulations, data analysis and AI methods. Using this strategy, I will mine tens and hundreds of thousands of real and hypothetical materials that already exist within the Material Genome, a global space of possible materials and their features. The focus of the project will be on Metal-Organic frameworks (MOFs) since they already show a particular promise for difficult separations. Specific scientific objectives of the project aim to i) understand what MOFs are promising for xylene separations ii) what structural features of MOFs are responsible for their specific behaviour iii) and then, using the AI models, design MOFs with superior xylene separation performance. The progress will be enabled by i) an outstanding research environment of the host group, Prof. Sarkisov, and the infrastructure of the University of Manchester; ii) interdisciplinary and intersectoral collaborations with the leading academics and companies (Prof. Goodwin, University of Oxford, Dr. Pullumbi, Air Liquide); iii) excellent training and professional development opportunities. Together, the environment of the fellowship and the pioneering research idea in application to the societally relevant and challenging problem, will make this project a stepping stone for my independent academic career.

Mots clés : mofs, separation, xylene isomers, molecular dynamics, grand canonical monte, carlo, flexibility, density functional theory, adsorption, multivariate data analysis, artificial intelligence

Participants :
- University of Manchester (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet METENZ (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Chemical synthesis through the activation of inert C-H bonds allows scientist to efficiently assemble complex organic molecules which have specific function. We aim to develop a novel class of metalloenzymes, where a transition metal catalyst is embedded into a genetically engineered protein, for rhodium catalysed asymmetric C-H activation reactions. We believe that the approach of incorporating a transition metal into a protein will allow for precise control of the chemical environment around the transition metal, allowing us to control many key outcomes of the chemical reaction such as enantioselectivity, regioselectivity and reaction rates. This technology will allow for the development of C-H activation reactions that have previously been inaccessible to the synthetic chemistry community.

Mots clés : metalloenzyme  chemical biology  asymmetric synthesis  c h activation

Participants :
- Colorado State University System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Columbia University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 251857.8 €
Projet MEGAKINE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Chemokines are small, secreted cytokines that activate membrane receptors belonging to the G protein-coupled receptor (GPCR) superfamily. The chemokine-receptor interactions control crucial physiological processes, but are also implicated in many pathologies, including atherosclerosis, inflammatory diseases, HIV infection or cancer, and hold a great potential for therapeutic intervention. Yet, although GPCRs are the target of about one third of currently marketed drugs, only three of them act on chemokine receptors, essentially due to poor structural understanding of the intricate interactions with their ligands. Indeed, about 50 chemokines and 20 receptors have been identified in humans. Their interactions require precise orchestration, as a chemokine may bind to several receptors, while a single chemokine receptor has multiple ligands. However, the structural determinants dictating ligand specificity and receptor activation remain elusive. Lately, cryo-EM has emerged as a ground-breaking technique for elucidating molecular structures but despite recent advancements, analysis of small proteins like receptor:chemokine complexes (∼50 kDa) is still challenging. In this project, we propose an innovative approach to increase the chemokine size, without altering its functionality, through a rigid insertion into a bulky scaffold protein. Such enlarged chemokines, called Megakines, will facilitate structural analysis of chemokine receptors. To prove this concept, we will first reformat the well-characterized chemokine CCL5 and use it in structural/functional studies with two clinically relevant receptors, CCR5 and ACKR2. The achievement of this project relies on the multidisciplinary combination of the excellent expertise in the chemokine field of the host laboratory and the protein engineering skills of the applicant. The proposed Megakine technology has the potential to revolutionize cryo-EM studies of chemokine receptors and facilitate the therapeutic development.

Mots clés : chemokines, gpcrs, cryo em, pharmacology, next generation structural chaperones, structural biology

Participants :
- Luxembourg Institute of Health (Luxembourg) — Coordinator, beneficiary, Recherche, subvention : 178320.0 €