Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet EXOGENESIS (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cells communicate with their environment in various ways, including by secreting vesicles. Some of these extracellular vesicles originate from endosomes, are loaded with proteins, lipids and RNAs and are called exosomes. Exosomes emerge as important players in physiological cell-cell communication, but also in various systemic diseases. Understanding how cells control the selective incorporation of ‘messages’ in their exosomes is thus essential, and such fundamental new knowledge may allow us to better understand cancer spread for example. Recently syntenin, a small intracellular adaptor protein, was identified as essential for the biogenesis of presumably a distinct class of exosomes that might be important for cancer cell communication and systemic invasion. Based on preliminary work, this study aims to evaluate the role of the membrane lipid phosphatidic acid in the formation of syntenin exosomes, their loading with cargo and their function in intercellular communication. A structure-function based approach is used, allowing if successful to pave the way for rational and innovative drug intervention. The fellowship will offer the applicant the possibility to receive an intensive training in biochemistry, cellular, molecular biology and drug discovery as well as to acquire important secondary skills which will pave the way for his career as an independent researcher.

Mots clés : exosome biogenesis, lipid binding studies, cell cell communication

Participants :
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet VIAR (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cellular innate immunity employs multiple ways to fight against invading pathogens, among them autophagy. Autophagy is an evolutionarily conserved homeostatic process in which damaged or surplus proteins are engulfed by double-membranes and subsequently degraded by the lysosome. Although initially described as non-specific, it has become evident that autophagy can selectively recognize and degrade cargos. While many pro-autophagy and therefore anti-viral factors have been studied in detail, our knowledge about prevention of excessive and imbalanced autophagy is limited. Autophagy has been previously recognized as a viral restriction mechanism for e.g. HIV. Even though HIV infection triggers autophagy, the virus evolved strategies to diminish this response by exploiting cellular factors, although key players and mechanisms involved are currently not well characterized. Moreover, since inhibition of enzymes by drugs is easier than activation, pro-viral autophagy restriction factors are promising targets for therapeutic approaches aiming to boost the autophagy. This proposal aims to combine expertise of the host (HIV) and the researcher (autophagy) to identify novel cellular pro-viral proteins mediating the restriction of autophagy using HIV as a model system. Human cells containing an autophagic flux reporter construct will be sorted according to autophagic flux after CRISPR/Cas9 mediated knockout of single proteins and gRNAs enriched in cells with high autophagic flux determined and HIV infection. Proteins identified in the innovative screen will be characterized in detail determining molecular mechanisms and viral interaction partners. Thereby, we gain fundamental insight into the balanced regulation of cellular autophagy upon viral challenges as well as viral evasion strategies. Furthermore, identified factors and molecular mechanisms will be relevant to unravel underlying mechanisms of diseases with imbalanced autophagy such as cancer and inflammatory diseases.

Mots clés : autophagy, anti viral strategies

Participants :
- University of Ulm (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €
Projet ENBIOMECH (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Cellulose and lignin constitute an unlimited natural resource for materials production, with the potential to substitute most of the currently used petroleum-based products. However, processing biomass into value-added products, such as cellulose nanocrystals (CNCs) and lignin nanoparticles (LNPs) is strongly limited by the insolubility these biopolymers, and thus generally requires large volumes of caustic or toxic chemicals and clean water, while generating hazardous waste. The ENBIOMECH project will first develop sustainable, environmentally friendly and efficient methods to produce CNCs and LNPs from biomass by employing enzymes in mechanochemical approaches, through which chemical transformations can be achieved in the solid state without solubilization of the biopolymers. Mechanochemistry will thereafter be used to convert the CNCs into a set of self-sorting nanoscale building blocks, by developing new facile methods for covalent surface modification of CNCs. Finally, various solid-state techniques will be investigated to reach new chiral nanoarchitectures from the obtained CNC building blocks, by gaining control over their supramolecular assembly. Switching to mechanochemical methods provides a fast and simple route to materials discovery, thus the ambitious ENBIOMECH project seeks to deliver a strong impact to the field of renewable bio-based materials by offering resource-conserving technologies to researchers and industry, aligned with the EU goals for the development of a green and sustainable economy. This project will bring together the researcher skilled in mechanochemical methods with the leading experts in cellulose chemistry and nanostructured biohybrid materials (supervisors), within a host institution strongly focussed on the development of bio-based materials and dedicated infrastructure ideally suited for supporting the proposed research.

Mots clés : mechanochemistry, cellulose nanocrystals

Participants :
- Aalto University (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 202680.96 €
Projet CENTEL (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Centrioles are evolutionary conserved organelles that template the formation of cilia, flagella and centrosomes. Centriole number dictates how many such structures form in a cell, so that controlling this number is essential for proper development and health. During sexual reproduction of animals, only the sperm contributes centrioles to the zygote, whereas centrioles are eliminated from the oocyte. The signals initiating and the processes executing centriole elimination remain largely elusive, both during oogenesis and in other developmental contexts where this can occur. Here, I propose to conduct state-of-the art live imaging and use novel quantitative super-resolution approaches in C. elegans to uncover the timing and molecular changes during oogenesis centriole elimination. Moreover, I will decipher the role of the RNA-binding protein CGH-1 in the timing of centriole elimination through a sequencing-based approach. Furthermore, I will conduct a proteomic screen to identify and characterize novel components required for oogenesis centriole elimination in worms. In a complementary approach, I will address the potential evolutionary conservation of centriole elimination mechanisms using the protist N. gruberi, which diverged from C. elegans over a billion years ago. I propose to also analyze in detail the dynamics of the elimination process in this system using deployed molecular markers. Moreover, I will conduct a proteomic screen to identify candidate centriolar proteins directing centriole elimination in N. gruberi. Furthermore, I will develop RNAi-mediated and CRISPR/Cas9 inactivation methods to test the function of candidate proteins in centriole elimination, thus also adding an important item to the toolbox at the disposal of scientists using N. gruberi. Overall, my work is expected to reveal whether centriole elimination is an ancestral mechanisms that has been conserved across eukaryotes and uncover the underlying molecular tenets of this process.

Mots clés : centrioles, elimination, organelle turn over, c  elegans, oogenesis, reproduction, gamete formation, naegleria gruberi, cellular differentiation

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

Cetaceans are apex predators with significant top-down roles in the marine ecosystem. The impact of these roles must be quantified by measuring energetics in the wild, which has proven difficult in cryptic, highly mobile animals. Current techniques to estimate energy use in free-swimming dolphins overestimate measured values by >200% or integrate energy expenditure over time scales too long to detect responses to specific events or conditions. Through RATE, I will make the first reliable estimates of energy expenditure in managed and free-swimming cetaceans by applying novel techniques from human medicine to extract information from respiratory sounds. RATE will (I) calibrate respiratory flow rates from breath sounds recorded in bottlenose dolphins, (II) apply this calibration to tag deployments on free-swimming, wild dolphins to derive reliable estimates of airflow and energy use, and (III) assess changes in respiratory condition in response to specific events or behaviours. RATE’s objectives require simultaneous respiratory measurements and acoustic recordings of each breath: a custom-built pneumotach placed over the blowhole of bottlenose dolphins will record respiratory flow rates and gases, while state-of-the-art acoustic tags (DTAGs) placed near the animal’s blowhole with suction cups concurrently record the sound of exhalation and inhalation. In accomplishing RATE’s Objectives, I will provide a quantitative and mechanistic framework to define the cost of existence of cetaceans in their natural habitats – a major breakthrough in marine mammal physiology that is directly relevant to the European Commission (EC)’s Marine Strategy Framework Directive. The novel methods I will develop for RATE will overcome existing limitations of measuring field metabolic rates in free-swimming animals, and will increase the resolution of field metabolic rate from days to seconds to revolutionize how we measure energy turnover of marine mammals in the wild.

Mots clés : bioacoustics, acoustics, marine mammals

Participants :
- Aarhus University (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet UNRAVELS (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Charge reorganization at the interface between oxides is the key feature of the emerging field of oxide-based electronics ("oxitronics"). Oxides like perovskites, ferrites, manganites (as SrTiO3, BaTiO3, Fe3O4, BiFeO3, CaMnO3) have become the building blocks for complex heterostructures coupling together at nanoscale different electronic and magnetic properties. Heterostructures can be used to create new outstanding electronic devices to go beyond the traditional silicon-based architectures. To control oxides electro-magnetic properties it's mandatory to completely understand the phenomena taking place at the nanoscale, like charge fluctuation and disproportionation, spin symmetry breaking or local chemical coordination experimentally measured with atomic-resolution and directly connected with the changes in the electronic and optical excitations spectra. This project wants to integrate sophisticated ab initio parameter-free simulations, based on Density Functional Theory and including many body effects, through Many Body Perturbation Theory and Time Dependent Density Functional Theory, with measurements in order to understand and to predict the mechanisms in oxides at nanoscale. These transferable and predictive parameter-free approaches will complement and guide the experiment. The direct comparison of calculated spectra with the experiment will permit to identify the electronic origin of the different excitations, their mutual interactions and their coupling driven by other degrees of freedom. The electronic structure of oxides (charge occupation, bandstructure, bandoffsets) across the metal-insulator transition will be calculated through the correct estimation of dielectric screening function; effect of dopants and strain on oxides and interfaces will be analyzed by calculating electronic and optical spectra. Moreover the side-by-side direct comparison between the calculated spectra and measured observables will permit to refine the theory and its ingredients.

Mots clés : oxides heterostructures, oxytronics, phase transitions, many body, ab initio paramter free calculations, tddft

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet ChildGesture (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Children typically learn their language in a multimodal environment as their caregivers interact with them with a variety of modalities. Especially, hand gestures are often used by caregivers to convey semantic information with speech. Thus, gestures are an important medium for children to understand speakers’ messages (McNeill, 1992). By using behavioural measures, previous studies have revealed that children and adults can comprehend and integrate information from iconic gestures and speech. For example, the Researcher found that it is hard for 3-year-olds to integrate information from speech and co-speech gestures, but 5-year-olds could perform with similar results to adults. However, behavioural measures do not provide access to the underlying neurocognitive processing of speech and iconic gestures, whereas neuroimaging techniques can provide more direct measures of the online cognitive process underlying the comprehension of co-occurring multimodal semantic information. Thus, this project examines neurocognitive processing of semantic information from gesture and speech in children and adults by using neuroimaging techniques such as EEG and fMRI. Study 1 investigates whether iconic gesture and speech are independently or bidirectionally processed in 3- and 5-year-olds and adults. Study 2 examines which brain areas are used to speech and gesture in children and adults. Two contributions are expected from this project. A practical contribution will be providing information to caregivers and teachers about how they should use their gestures to foster childrens’ language acquisition. A theoretical contribution will be providing neurobiological data on how gesture and speech are processed in children and adults. Through this project, the Researcher will obtain knowledge about neuroimaging research and his expertise will contribute to the Host institution by providing knowledge about childrens’ communication research.

Mots clés : gesture, multimodal integration, neurolinguistics, children, fmri, language acquisition

Participants :
- Radboud University Nijmegen (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 177598.8 €
Projet EpiLIVER (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cholangiocarcinoma (CCA) is a devastating type of liver cancer that presents late, is difficult to diagnose and associated with a high mortality. Although worldwide the epidemiological trend is mixed, in the EU it has been steadily increasing for the last decade. Treatment is limited to tumor resection, which is not applicable in the vast majority of cases. The lack of any approved chemotherapy-based treatment is partially due to the poor understanding of the molecular mechanisms involved in the response to these drugs. Taking advantage of the comprehensive panel of established and primary CCA cell lines in the host PI’s lab and my expertise on the DNA damage response (DDR) and repair field, my proposal offers a new approach in this scenario by characterizing the DDR of CCA cells. This study will be focused on the DDR-related chromatin remodeling SWI/SNF complex. In recent works, mutations in this family of proteins were identified in 47% of all CCA cases analyzed through whole exome sequencing, hence providing a relevant rationale in studying this complex. First, I will identify candidate markers of all known components of the SWI/SNF complex, based on RNAi high-throughput analysis. I will then perform direct and quantitative measurements of the DNA repair activity in CCA cells, specifically related to homologous recombination repair (HR) by rapid and sensitive reporter assays. And lastly, I will determine the proteome dynamics in the CCA context. There are two exclusive novelties on this approach: (1) the described novel methods will be employed in the Hepatology field for the first time; and (2) the use of primary CCA cells will enable me to directly compare observations in culture with clinical outcome. This proposal will not only contribute to the understanding of a limited understood area in liver cancer, but also holds great promises for future clinical use, where DDR-based drugs are the clinical mainstay

Mots clés : cholangiocarcinoma  cca, rnai screening, dna damage response  ddr, homologous recombination  hr, snf complex, drug treatment

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet MiRCHOL (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cholangiocarcinoma (CCA) is a dismal type of liver cancer which incidence has more than doubled the last 20 years and mortality rate in Europe alone increased 37%, reflecting the limited treatment options. In >70% of patients CCA is unresectable due to advanced stage of disease at diagnosis, resulting in a 5% 5-year survival rate. CCA is characterized by molecular and clinical heterogeneity, complicating therapy and assessment of drug efficacy. Tumor heterogeneity is emphasized in limited response of therapy (drug resistance) and besides genomic instability a likely consequence of deregulated pathways under control of microRNAs (miRs). Each miR can regulate multiple genes/pathways, directly linking them to tumor heterogeneity. Deregulation of miRs can cause/control chemoresistance in other cancers, but in CCA their role is yet unclear. Thus, detailed characterization of miRs in CCA, focusing on their impact in drug resistance is urgently needed. Hence, I have 3 specific aims of this proposal: to 1) characterize the deregulated expression pattern of miRs involved in CCA pathogenesis and integrate this data with transcriptomes obtained from matched patients; 2) determine the role of deregulated miRs in control of chemoresistance, and 3) modulate by genome-editing key deregulated miR(s) targeting chemoresistant genes using the novel `CRISPR-Mir’ method. Achievement of these aims will yield key new insights into the role of miRs in orchestrating CCA progression and metastasis, as well as their involvement in drug resistance. My findings will have an impact on the society and in particular in patient outcome. Dr. Andersen, a world-wide expert in the molecular pathogenesis of CCA with a vast experience in genome medicine, will supervise the project. Successful completion of this proposal will enable me to expand my scientific expertise (plus technical and transferable skills) and to establish myself as an independent researcher in hepatobiliary and translational research.

Mots clés : bile duct cancer, tumor heterogeneity, drug resistance, micrornas  mirs, crispr mir genome editing

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet SILIA (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cilia and flagella are evolutionary conserved organelles indispensable for vital processes in eukaryotic organisms, such as environment sensing, cell motility, signaling and development. Broad spectrum of ciliary functions, together with omnipresence of the cilium throughout human body, explains the range of symptoms associated with congenital ciliary disorders called ciliopathies. On the other hand, cilia are essential for survival of parasites, such as trypanosomatids, in the host. Therefore, cilia are of great interest as a potential therapeutic target. The ciliary tip is an essential ciliary domain; it provides capping and mechanical stabilization of the ciliary cytoskeleton, it is a turning point of the intraflagellar transport trains, a sole place of cilium growth and a place of budding of signaling vesicles. Yet the tip is the most enigmatic of all ciliary domains, with structures constituting the ciliary tip largely unknown. This hampers our understanding of how are the tip-related processes brought about and orchestrated. To gain insight into the dynamic ultrastructure od the ciliary tip, I will develop a novel technique for cryogenic correlative light and electron microscopy based on solid immersion lens (SIL) optics. I will integrate the resulting imaging data with the tip proteome project project carried out by the host lab and provide mechanistic understanding of the resulting tip model by employing top-down synthetic biology and in vitro reconstitution approaches. Key achievements of this project will include: (i) development of the cryo-SIL technique and (ii) unraveling the functions of the the ciliary tip domain, which will broaden our knowledge of the principles of self-organization of biological systems.

Mots clés : cilia, flagella, axoneme, microscopy

Participants :
- Czech Academy of Sciences (Rép. Tchèque) — Coordinator, beneficiary, Recherche, subvention : 156980.64 €