Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet PainDynamics (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Chronic pain is a major health care problem in Europe which results in huge economic costs. Available cognitive-affective accounts of pain, distress and disability suggest that attention plays a pivotal role in the development and maintenance of pain problems. In particular the presence of an attentional bias towards pain-related information (AB) is thought to initiate or exacerbate pain problems in chronic pain patients. Despite the intuitive appeal of this idea, findings are inconsistent. In the current project I argue that inconsistent findings in AB research are due to both conceptual and methodological limitations of previous research. From a conceptual standpoint, I argue that the presence of inconsistent findings is owe to the conceptualization of AB as a stable trait-like or habit-like process. Instead, I propose to conceptualize AB as a temporally dynamic, fluctuating and enfolding phenomenon that varies over time and across contexts. From a methodological standpoint, I furthermore argue that varying empirical support may also be due to limited ecological validity in AB research. I propose that the ecological validity could be increased by using somatosensory stimuli instead of linguistic stimuli and by investigating AB for pain-related information and key variables in everyday situations instead of in a single laboratory session. In the current proposal, I will address these conceptual and methodological challenges via (1) the development and validation of a novel ecologically valid paradigm to assess AB, and (2) an investigation of key hypotheses concerning the role of AB in chronic pain using a novel ecologically valid approach. Increased understanding of the occurrence, dynamics and implications of AB in varying daily life contexts represents an important step in advancing theoretical models on chronic pain. Furthermore, current findings may also help to attune clinical interventions to the needs of each individual pain patient.

Mots clés : attention bias, chronic pain

Participants :
- University of Luxembourg (Luxembourg) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172800.0 €
Projet KiT-FIG (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Chronic renal failure affects ~10% of the world population and can gradually lead to end-stage renal disease (ESRD) requiring kidney transplantation. Despite the huge progress of immunosuppressive treatments, the host immune response against the graft still leads to rejection in many cases, with an average graft half-life of 10 years. Triggers leading to graft rejection are still largely unknown and need to be studied beyond the well-recognized impact of HLA mismatches. I propose here to explore the effect of functional immunogenomic parameters beyond HLA mismatches (HLA alleles, HLA gene expression regulation, KIR...) on kidney transplantation outcomes (cellular and humoral rejections, tolerance). To achieve this present-day clinical challenge, I will combine innovative bioinformatics tools and modern genomics to perform cutting edge association studies: the Kidney Transplantation - Functional ImmunoGenomics (KiT-FIG) project. KiT-FIG ultimate goal is to provide new evidence to improve graft allocation and transplanted patients’ management. Objective A is to develop innovative methods of HLA statistical inference to gain precision and generate additional functional immunogenomic parameters. Objective B is to apply these novel methods to investigate the impact of immunogenetics on immunological outcomes related to kidney transplantation. This objective will rely on genetic association studies to unlock the major scientific challenge of large and unexplained variability observed in renal graft survival. KiT-FIG ambitions to develop new innovative bioinformatic and biostatistics tools to capture the complexity of HLA-related immune responses. These tools will be freely accessible to the community to expand immunogenetic studies of other diseases. The implementation of these tools in the context of kidney transplantation outcomes will increase the understanding of underlying immunological mechanisms and will contribute to improve graft survival and patient management.

Mots clés : immunogenomics, bioinformatics, imputation, kidney transplantation

Participants :
- Nantes Université (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196707.84 €
Projet Dual-NanoMAE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Chronic ulcers are a major cause of morbidity and mortality with increasing prevalence. Ulcer healing is the ultimate therapeutic goal. Control of reactive oxygen species (ROS) and infection prevention are key factors to minimize inflammation and tissue damage in the healing process. The aim of this work is to take advantage of two remarkable properties of the green microalgae C. zofingiensis - the production of the highly antioxidative astaxanthin and a large amount of antibacterial fatty acids (FA) – and to combine them in a new therapeutic lipid nanoparticle for ulcer therapy (Figure 1). Thereby the project increases the pharmaceutical availability of the hydrophobic drug astaxanthin, circumvents its low bioavaliabality and chemical stability, all limiting its pharmaceutical significance until today. Nanoparticles will be characterized for their physical–chemical properties, cytotoxicity, in vitro proliferation enhancement, and wound healing properties toward normal human cells. Antioxidant activity of Dual-NanoMAE on 2D and 3D cell culture models will be monitored with FLIM-ROX, a sophisticated and sensitive technique developed by Prof. Dr. Ulrike Alexiev. Antimicrobial activity of nanoparticles will be evaluated against two reference biofilm forming bacterial strains, Staphylococcus aureus and Pseudomonas aeruginosa. Finally, the capability of Dual-NanoMAE to promote ulcer healing will be evaluated on a biofilm infected ulcer model based on human cells.

Mots clés : nanoparticles, chronic ulcers, oxidative stress, microalgae extract

Participants :
- Freie Universität Berlin (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 162806.4 €
Projet ResolvCiliaTip (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cilia are conserved microtubule-based organelles, which extend from the cell surface and have diverse motility and sensory functions, integrating developmentally important signalling pathways. As such, defects in ciliary assembly and/or function can lead to developmental disorders and multi-systemic genetic diseases, termed ciliopathies. The ciliary tip, a region between microtubule ends and the ciliary membrane, is implicated in cilium assembly, disassembly, signalling, and motility. Few ciliary tip proteins identified so far are mutated in ciliopathies. Yet the complete identity of microtubule associated proteins at the ciliary tip of both primary and motile cilia, and the mechanisms underlying their regulation of ciliary microtubule dynamics and geometry, remain unknown. The proposed research will resolve the link between the ciliary tip geometry and function both in primary and motile cilia, as well as molecular mechanisms controlling the microtubule end dynamics at the ciliary tip and identify the full repertoire of ciliary tip components. The research will focus on functional characterization and interactions of the CCDC66 protein, which mutations cause progressive retinal degeneration, the most frequently observed phenotype across different ciliopathies. The CCDC66 is a recently identified tip component of the primary cilia and preliminary experiments suggest the axonemal and ciliary tip localization of CCDC66 in motile cilia. Therefore, we will investigate both the localization and function of CCDC66 at the primary and motile cilia tip with the nanometre-scale precision. We will elucidate the effect of CCDC66 on microtubule end dynamics using the biochemical assays and resolve the molecular proximity map of the CCDC66 using BioID method and proteomics. The results of this project, predicted to better characterize the causative genes of ciliopathies, could make positive impact on clinical studies and enhance diagnostic approaches in future.

Mots clés : primary cilia, motile cilia, ciliopathy, ccdc66, axoneme, signaling, miniturboid proximity mapping

Participants :
- Koç University (Turquie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 145355.52 €
Projet INNERVATE (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Circa 30 million people in Europe suffer from life-threatening rare diseases, which are poorly understood. This major societal burden forces patients into endless paths for a diagnosis often without cure. EU cooperation efforts between countries contribute to improve research and visibility of these diseases with a primary role of the ‘Ospedale pediatrico Bambino Gesù’ (OPBG, Italy). Here, via next generation sequencing technology, Dr. Tartaglia recently described new genetic variants, including some in the tubulin cofactors TBCE and TBCD which alter microtubules (MTs) dynamics (crucial for brain development and maintenance) and cause previously undescribed early onset neurodegeneration. Yet the underlying pathogenic mechanisms and impact on the brain physiology remain elusive. Given the difficulty to reproduce brain physiology in vitro and its general inaccessibility, a vertebrate model amenable to genetic and whole-brain in vivo investigation is necessary. With its rapid and transparent development and genetic and imaging tools improving continuously, the small teleost fish zebrafish is ideal. I will monitor live MTs behaviour and cellular processes (e.g. cell division, axons formation and innervation) in the precursor and mature neurons of zebrafish TBCE and TBCD mutants, focusing on motoneurons. To this aim, I will combine my expertise in fish neurobiology with the host’skills in human genetics (Dr. Tartaglia) and fish gene editing (Dr. Del Bene, France). In line with the current EU efforts, this work will advance our understanding on rare genetic variants causing neurodegeneration. Deciphering the role of MTs dynamics on brain physiology will be relevant also for common brain disorders and exome sequencing of undiagnosed patients will further contribute to a genotype-phenotype catalog. Via an intensive transfer of knowledge, the project will increase EU multi-disciplinary competence on rare disorders in general, providing new models for therapy development.

Mots clés : rare brain diseases, neurodegeneration, microtubules, motoneurons, neuroimaging, zebrafish, in vivo

Participants :
- Istituti di Ricovero e Cura a Carattere Scientifico (Italie) — Coordinator, beneficiary, Recherche, subvention : 183473.28 €
Projet InterDemo (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : TERMINATED

Claims from hitherto excluded indigenous groups have led to the rewriting of constitutions in Bolivia and Ecuador to recognize intercultural democracy. At the same time, indigenous environmental justice movements have increased their contestation of hydrocarbon extraction – and recently mining – due to their socio-political and ecological impacts. Analysis of these movements to date has focused on the consequences of conflicts, but less so on their socio-political and ecological drivers. While evidence has demonstrated the role of an increasing social metabolism as a driver of extraction, less attention has been paid to power relations and competing socio-political forces. These deeply influence the possibilities for a democratic control of the extractive sector, a crucial factor for achieving environmental justice and sustainability. This research aims to unpack the power relations that lie beneath the biophysical flows of expanding resource extraction in the intercultural democracies of the Andes. Two mining-related conflicts in Cuenca Poopó (Bolivia) and Intag (Ecuador), where indigenous organizations claim greater environmental justice specifically through self-determination as part of intercultural democracy, will be analyzed applying mixed methodologies: quantitative analysis of biophysical flows and qualitative analysis of interviews and data. This research will potentially show how ecological and metabolic drivers limit indigenous groups’ democratic participation through multi-scale power relations around resource appropriation, thereby improving the understanding of the political dimensions of these conflicts and informing more sustainable policies for extractive sectors. Training at the host institution (ICTA) will facilitate this research by complementing the candidate’s knowledge of political theory with skills in metabolic analysis and the interdisciplinary approach to environmental justice that forms the basis of ICTA’s world-renowned research.

Mots clés : political ecology, environmental justice, intercultural democracy, plurinational state, power relations, indigenous peoples, socio ecological conflicts, mining, latin america, sustainable policy

Participants :
- Autonomous University of Barcelona (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 158121.6 €
Projet HodgkINsights (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Classical Hodgkin Lymphoma (cHL) is one of the most common cancers in young adults. While chemo-radiotherapy is effective, many patients continue to die of cHL or to suffer long-term treatment toxicities, such that more effective and less toxic drugs are needed. Studying the mechanisms underlying the puzzling biology of cHL (the only B cell-derived lymphoma loosing its B-cell identity) should illuminate its pathogenesis and possibly aid in developing better therapeutic strategies. In this project, I will study the function of mutations in the DNA binding domain of the STAT6 transcription factor, which the host laboratory identified as one of the most frequent genetic lesions in cHL. I will perform genome-wide ChIP- and RNA-seq studies to uncover aberrant gene expression regulation and occupancy by mutant versus wild-type STAT6 in cHL versus non-Hodgkin lymphoma (NHL) cell lines, and investigate their functional consequences at the cellular level. I will then express mutant STAT6 in germinal center (GC) B cells, the cHL cell of origin, to evaluate their role in early lymphomagenesis. Because genes mutated in cHL greatly overlap with those altered in NHLs, from which cHL is strikingly different, I will also explore whether unidentified mutations in non-coding regulatory regions may underlie the peculiar cHL pathogenesis. Recurrent somatic non-coding mutations will be identified through whole-genome sequencing of primary cases and will be annotated to the non-coding elements specifically active in cHL cell lines, which I will identify through RNA- and ChIP-seq for key histone marks. Finally, I will use appropriate techniques (e.g., genome topology and CRISPR editing) to assess how such mutations may alter regulatory networks important for cHL biology and identity. The project will also expand my expertise in genomic regulation in lymphomas, boost my research productivity after a career break, and support my transition to an independent investigator.

Mots clés : hodgkin lymphoma, stat6 mutations, non coding functional mutations

Participants :
- University of Perugia (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 275209.92 €
Projet UMOTA (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Classical computers quickly hit the brick wall when asked to model the behavior of interacting quantum systems. For example, calculating the time evolution of a quantum system consisting of only 40 interacting spin-½ particles is believed to be fundamentally impossible on a classical computer. Fortunately, the direct investigation of such systems is coming into the reach of today’s most powerful quantum simulators. In this approach, a controllable quantum system is used to model the behavior of other less accessible systems of interest. I plan to make a versatile, reconfigurable array of strongly-polar Calcium Monofluoride (CaF) molecules, and investigate its utility as a scalable quantum simulator. These ultracold molecules have long lifetimes and interact over large distances via their strong electric and magnetic dipole moments. They can thus be used to investigate a wide range of many-body quantum phenomena and are promising candidates for the simulation of lattice spin models, which are omnipresent in condensed matter physics. In the Center for Cold Matter at Imperial College London, CaF has recently been magneto-optically trapped and laser-cooled to a record-breaking temperature of 50µK. As an MSCA fellow I will build upon these results. I will develop techniques to confine a single CaF molecule in an optical tweezer trap, then assemble a controllable array of molecules using multiple tweezer traps, and finally investigate the entangling dipole-dipole interaction between two neighboring molecules by coherent microwave control. These experiments will take place in a complexity regime where results can still be numerically simulated and will thus serve as benchmark tests of a future scalable quantum simulator.

Mots clés : ultracold molecules, polar molecules, quantum simulation, optical tweezers, optical dipole traps

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet DUBs26S (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Clearing-up old or redundant proteins is essential for cells to live; this job is largely done by 26S Proteasome. The multisubunit complex – 26S Proteasome – is extraordinarily conserved throughout all eukaryotic phyla, in terms of subunit composition and overall structure. However, in preparation of this research proposal, the Researcher found a novel association of 26S proteasome with a clinically important deubiquitinating enzyme (DUB), USP9X. In a subset of proteasome purified from human tissue by the Researcher, USP9X was in fact the major DUB replacing commonly reported enzymes (USP14, UCH-L5). This finding shatters the notion of proteasome as a static, fixed, complex, and opens up the search for expanded spheres of interaction. The crux of this MSC-IF action is the reciprocal relationship between 26S proteasome and USP9X. Using myriad experimental tools at his disposal, the Researcher proposes to unravel how this novel association tweaks each of their respective enzymatic properties. Incorporation of USP9X may alter substrate specificity and processivity of proteasome, as well as its own enzymatic properties. Even in the immediate term, this proposal will realign research efforts – both basic and applicative – towards USP9X as the new drugable target in the ubiquitin-proteasome system. This new enzymatic active site on proteasome complexes will instigate investigation into the cause of USP9X in neurodegeneration and various cancers. This MSCA-IF fits current European challenges to increase healthy life span by proposing strategies for drug design against DUBs of clinical relevance. Two host labs are committed to provide the Researcher with the best training and support to bring his research to fruition and embark his independent career. Novel experimental findings embellished with new technical competencies and networking experience ensures the Researcher’s future career goals.

Mots clés : ubiquitin, 26s proteasome, deubiquitinase enzymes, dubs, protein protein interaction, cancer, neuronal differentiation, small molecule inhibitors

Participants :
- Technion – Israel Institute of Technology (Israël) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 182509.2 €
Projet CliMOC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

CliMOC is a proposal to fund a fellowship to be carried out by the Experienced Researcher (ER) Katinka Bellomo at host institution Polytechnic University of Turin, Italy (POLITO) in the department of Environment, Land and Infrastructure Engineering under the supervision of main host professor Jost von Hardenberg. The aim of the proposed work is to investigate the role of the Atlantic Meridional Overturning Circulation (AMOC) on climate impacts over Europe. Previous studies have shown an important role for the AMOC in modulating global climate change, in particular over the Northern Hemisphere and Europe. An AMOC collapse has been identified as a possible trigger of the initiation of Ice Ages. However, the influence of AMOC in future climate change is still unclear given the large inter-model uncertainty in the decline rate of AMOC, and the concurrent climate changes due to increasing concentrations of well-mixed greenhouse gases in the atmosphere. In this proposal, we advance some hypotheses for the role of AMOC in the current climate and future climate change, and we propose a hierarchy of climate model simulations to separate the role of AMOC from other processes. More specifically, we plan to implement a slab-ocean model component in the EC-Earth global climate model. Using the ocean heat fluxes from a fully-coupled EC-Earth simulation in which the AMOC is artificially weakened, we will be able to run a slab-ocean EC-Earth simulation with a high-resolution atmospheric component, which will let us investigate the role of AMOC in future climate change impacts over Europe. This work will help reduce the uncertainties in projections of future climate change by constraining the influence of AMOC.

Mots clés : atlantic ocean, climate models

Participants :
- Polytechnic University of Turin (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183473.28 €