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

Internet of Things (IoT) is a booming market that will impact our daily life with the deployment of billions of electronic devices. Digitalization is therefore a priority of the EU policy. Massive adoption of IoT requires energy autonomy and wireless devices. Powering such devices remains a challenge that WiPASS wants to tackle. WiPASS project is aimed at developing an innovative and disruptive Wireless Power Transfer (WPT) technology exploiting a low-frequency variable magnetic field to send electric power over the air between an emitter and receivers based on an electromechanical system. This power is then used to supply electronic functions such as sensors and actuators. Compared to other WPT technologies, the one proposed in WiPASS operates at lower frequencies enabling to reach higher transmission distances with better penetration in conductive media. Proofs of concept of this technology have been developed by The Researcher, Nicolas Garraud, during his PhD thesis in the University of Florida. The Researcher now wants to further develop and optimize this technology, to solve the limitations and to study its commercial relevance once integrated in an electronic system. The Researcher will carry out this research in CEA-LETI (France), renowned in Energy Harvesting and Wireless Power Transfer technologies, under the supervision of Sebastien Boisseau, Energy Harvesting Expert. WiPASS project will be a springboard toward a Research Team Leader position in 5 to 7 years in a European public or private actor for The Researcher. WiPASS will boost the career of The Researcher thanks to the new skills he will acquire, an improved visibility, a higher maturity in communication, project writing and management, and exchanges with academic and private partners of CEA-LETI. It will also boost IoT deployment in Europe by solving the issue of the energy autonomy of wireless devices, paving the way to new breakthrough in Health, Smart Cities, Transport and Industry.


Participants :
- Commissariat à l’énergie atomique et aux énergies alternatives (France) — Coordinator, beneficiary, Recherche, subvention : 196707.84 €
Projet TOPOGRAPHYSENSING (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Intestine epithelium consists of spatially segregated cells that organize into groups of various functions at different locations of the 3D curved epithelial monolayer. How geometric cues contribute to the maintenance of the sophisticated epithelial architecture and dynamics in 3D remains unknown until now. Recently, the Ladoux's laboratory has found that EpCAM-modulated cell contractility associated with the epithelial monolayer polarity, cytoskeletal arrangement, and cell-cell adhesion in 3D context. In contrast to 2D context, the EpCAM-defective tissue shows a loss of collective cellular spatial organization and forms a disordered multi-layered epithelium when exposed to substrates of 3D topographies. In addition, Ankyrin-G and α/β-spectrin network which participates in cortical tension modulation was identified as the main interacting partner with EpCAM in epithelial cells. These observations lead us to hypothesize that EpCAM allows the tissue to sense and conform to complex 3D topographies in an orderly manner. However, the molecular mechanisms and other related functions of EpCAM-mediated mechanotransduction remain unknown. As large scale mechanosensing has been shown to occur primarily through the actin cytoskeleton which permeates the tissue to form a network, we aim to understand the interactions between the EpCAM-mediated pathway and actin modulation and/or E-cadherin adhesion sites that may allow 3D topographical sensing. Our working hypothesis is that EpCAM forms an integral part of the cellular responses to topographic cues that has a more general role in controlling epithelial architecture and dynamics through the regulation of actomyosin networks, or vice versa. Here, we propose to scrutinize EpCAM-mediated mechanotransduction by generating a platform with precise control of geometric factors and microenvironmental cues using a range of multidisciplinary approaches including microfabrication, biophysics, and advanced molecular biology techniques.

Mots clés : 3d topographic cues, epcam, actin cytoskeleton, mechanotransduction, intestinal epithelium, adherens junctions

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 134600.08 €
Projet METCLL (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Intra-tumoral heterogeneity allows all form of cancers to undergo an evolutionary process in response to selective pressures, such as therapy, which results in a more aggressive disease. As chronic lymphocytic leukemia (CLL) are particularly amenable to evolutionary investigations, it has been shown that CLL’s capacity to escape therapy is linked in to genetic evolution, which is fueled by intra-tumoral heterogeneity. Aberrant DNA methylation can also dysregulates genes involved in CLL pathogenesis. Like genetic alterations, DNA methylation modifications are heritable and subject to natural selection. Landau et al have studied sub-population DNA methylation heterogeneity in CLL and uncovered a large amount of stochastic variation. The acquisition of stochastic DNA methylation alterations enhances epigenetic plasticity and creates a non–genetically encoded source of heterogeneity, fuelling tumour cells in their search for superior evolutionary trajectories. These new data modify the way we understand cancer epigenetics, and offer a new field of investigation: identify “epidrivers”, i.e. somatic epigenetic alterations leading to cancer-heterogeneity and which are positively selected through cancer evolution. Thus, I will pursue in this project four independent yet complementary aims. During my outgoing period I will robustly identify epidrivers from bulk next-generation sequencing (NGS) (Aim 1) and from single-cell NGS (Aim 2) of a large CLL cohort. Candidate epidrivers uncovered from the first two aims, will be further validated in a large-scale epigenome editing screen (Aim 3). Then building upon technological development from Aim 2 and 3, during my returning period at Curie Institute, I will extend this important paradigm to solid tumor by exploring breast cancer evolution (Aim 4). This integrative analysis of epigenetic heterogeneity will enable the reconstruction of tumor epigenetic population complexity and how it shapes disease relapse and evolution.

Mots clés : dna methylation, clonal evolution, breast cancer

Participants :
- Cornell University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Institut Curie (France) — Coordinator, beneficiary, Recherche, subvention : 264668.4 €
Projet PANDORA (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Intracranial aneurysms (IA) with and without subarachnoid haemorrhage (SAH) linger as a potentially devastating clinical problem. Current therapeutic options are limited to invasive therapies, namely microsurgical clipping and endovascular treatment, both of which carry a significant risk of procedural morbidity. Increasing evidence points to inflammation as one of the leading factors in the pathogenesis of IA. Intrasaccular thrombus formation is a common feature of intracranial aneurysm occurring in 25% of unruptured and 70% of ruptured IA. In addition to forming clots, activated platelets support leukocyte recruitment. This cross-talk is a common feature in thrombo-inflammatory vascular disease. Despite these deleterious aspects of platelets, they also prevent local hemorrhage in inflammatory situations independently of their ability to form a platelet plug. The pathophysiological evolution of IA events seems driven by complex cellular interactions between different cell types including platelets, leukocytes and vascular cells (endothelial cells, smooth muscle cells). We hypothesize that the role of platelet roles may evolve throughout the development of IA: initially playing a protective role of in the maintenance of the blood brain barrier in response to inflammation and contributing later to intrasaccular thrombus formation. Therefore, altered platelet function may result in a loss of protection against vascular inflammatory insults. The main objective of this proposal is to better understand and decipher platelet mechanisms during IA formation and rupture. In this current application, we will (i) define platelet activation mechanisms in the development of IA and the impact on the blood-brain barrier integrity, (ii) test efficient anti-platelet therapies in the development and rupture of IA, (iii) define an efficient therapeutic window to intervene on platelet activation (prevention or intervention).

Mots clés : platelets, leukocytes, vessels

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

Introductions of animal hybrids borne of exotic species and arboviruses represent costly anthropogenic environmental changes. These processes become intertwined if hybrids become arbovirus reservoirs. How does the admixed composition of hybrid immune genes, specifically Major Histocompatability (MHC) class I, affect the hybrid susceptibility to pathogenic disease? A human hybridization study suggests that genetic introgression gives hybrids an immunological selective advantage, but such studies are few. Europe and Brazil have been impacted by arboviruse outbreaks from dengue, chikungunya, and West Nile. Because human travel intimately links these two regions, this close relationship augments the chance of arbovirus transmission between them. Hybrids of the primate Callithrix genus occur in many highly urbanized Brazilian regions of arbovirus outbreaks, and the hybrid parental species are carriers or susceptible to arboviruses infections. Here we propose to adopt emerging, portable sequencing technology to test the hypothesis that hybrids have a selective advantage to infectious disease susceptibility using the classical Callithrix MHC class I Caja-G/F segment. Further we will investigate diversity, natural selection, and genetic introgression at the genomic level and Caja-G/F segment in wild hybrid and non-hybrid Callithrix. By using this entire segment, this study powerfully harnesses the potential of the MHC region as a pillar of evolution studies and invigorates a paradigm shift in how such an important genomic region is studied. Additionally, this project will be the first to apply cutting-edge portable sequencing technology to study mammalian biodiversity, evolution, and wildlife health- a notion that democratizes the generation of genomic data. Finally, the results of the project will stimulate innovation in European and Brazilian zoonotic disease monitoring through improvements to mathematical models of disease transmission and public health guidelines.

Mots clés : hybridization, arbovirus, major histocompatability class i, new world primate, callithrix, brazil, introgression, positive selection

Participants :
- Leibniz Association (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 171460.8 €
Projet MOLiNTEL (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Ionotropic Glutamate receptors (iGluRs) influence the timescales at which neurons communicate with each other. The dynamics and flexibility of the response of iGluRs to neurotransmitter binding give rise to the synaptic plasticity responsible for normal human intelligence. Dysfunction of the iGluRs is causally responsible for diseases such as Alzheimer's and Amyotrophic lateral sclerosis. It is therefore medically important to understand how the structure-function relationship in the iGluRs operates at the molecular level. Many drugs attempt to target iGluRs to treat neuropathologies. However, due to the inherent complexity of the dynamics of iGluRs it is difficult to accurately target the causative function of the iGluRs thus making it difficult to form a viable pharmaceutical strategy, without insight into the dynamics of iGluRs at the atomic level. Additionally, although the individual members of the iGluR family are structurally very similar, they display very different kinetic and allosteric behaviour. The proposed project aims to focus on the comprehensive picture of the comparative dynamics of the members of the iGluRs. In close collaborations with experimental and computational methods development groups, I plan to investigate how the relatively small differences in the structures of the iGluRs give rise to the complex behaviours of the iGluRs. This will be accomplished via state of the art Molecular Dynamics (MD) simulations and a large library of computational thermodynamics techniques. From this dataset, using Machine Learning (ML) techniques in combination with Markov State Models (MSMs) I will create robust and testable models that can determine the commonalities and variances between the dynamics of the members of the iGluRs while throwing light on their mechanisms of action.

Mots clés : biophysics, biological physics, scientific computing, computational science, biomolecular simulation, computational neuroscience

Participants :
- University of Helsinki (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 202680.96 €
Projet FourFeFourS (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Iron-sulfur [Fe-S] clusters play a vital role in numerous cellular functions. They are a sine qua non for cellular energy production and maintenance of genomic stability. Therefore, elucidation of the biogenesis of [2Fe-2S] and [4Fe-4S] proteins is of utmost importance for basic science in its broadest sense, as it is for ongoing efforts to establish their relevance to human disease and their utilization for biotechnological production of fine chemicals in microorganisms. The iron-sulfur cluster (ISC) assembly process is responsible for incorporating the inorganic cluster into [Fe-S]-associated proteins in the mitochondria. Cytosolic and nuclear [Fe-S] protein assembly that dictates cellular iron concentrations and DNA integrity outside of the mitochondria also depends on the function of the ISC machinery. The mitochondrial ISC biogenesis machinery entails at least 17 proteins, yet how the proteins for [4Fe-4S] maturation work in a unified manner to produce the active cluster and transfer it to target proteins remains poorly understood. FourFeFourS intends to discover the underlying mechanisms of [4Fe-4S] biogenesis in the mitochondria, which could shed new light into how dysfunction of the proteins involved may lead to fatal diseases. To this end, studies will combine a biochemical reconstitution assay of the biological process utilizing isolated ISC proteins in conjunction with spectroscopic and spectrometric experiments that elucidate detailed protein function and molecular structure. In carrying out this cutting-edge research under the tutelage of a world-leading expert on iron-sulfur protein biogenesis, I will expand my expertise within the multidisciplinary field of biochemistry – in particular my understanding of the roles of metal ions in biology. In the process, I will build a solid foundation for a future research career as a group leader within the European Union.

Mots clés : fe s  cluster biogenesis, fe s  cluster trafficking, iron homeostasis, mitochondria, disease, reconstitution assay, mechanism, nuclear magnetic resonance, x ray crystallography

Participants :
- Philipps University of Marburg (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 159460.8 €
Projet PhyCaR (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Ischemic heart disease is the main cause of death in Europe and the world, and its main manifestation is myocardial infarction (MI). The MI leads to loss of heart tissue, tissue scarring associated with fibrosis, dysfunction and heart failure. The pathophysiological basis of heart failure in humans lies in the heart's inability to regenerate. Adult cardiomyocytes (CMs) perform mitosis after MI, but their proliferation rate is extremely low for restoring normal cardiac function. During development, low levels of intrauterine oxygen promote the proliferation of CMs, which decreases postpartum due to the metabolic adaptation that implies exposure to atmospheric oxygen. Induced hypoxia in adult mammals promotes proliferation of CMs, and is required for cardiac regeneration (CR) of teleost such as zebrafish. However, the mechanisms that mediate these effects are unclear. Systemic exposure to hypoxia has been proposed as a strategy to promote CR; however, its adverse effects on other vital organs limit its clinical use. Here, we have proposed the generation of a temporary and localized hypoxia in the infarcted area of the heart. To achieve this, we will synthesize fibrin scaffolds bearing FG-4592 - an agent that mimics the effects of hypoxia (pseudohypoxia) - using bioprinting 3D. Besides, scaffolds will be loaded with CMs derived from Induced pluripotent stem cells (iPSCs-CMs), and will be implanted in MI models of pigs. Delivery of FG-4592 and iPSCs-CMs through scaffolds in the damaged myocardium would promote proliferation of resident CMs and cell turnover, respectively. Additionally, we will explore two mechanisms by which hypoxia could promote CR, remodeling of the extracellular matrix and angiogenesis mediated by angiopoietin-like 4 (Angptl-4). This project is a necessary effort to materialize the latest advances in hypoxia and CR by combining cell therapy with a cutting-edge technology in the tissue engineering field, 3D bioprinting.

Mots clés : cardiac regeneration, hypoxia, pseudohypoxia, hypoxia mimetic agents, scaffolds, bioprinting 3d, induced pluripotent stem cells, cardiomyocytes, angiopoietin like 4, ecm remodeling, angiogenesis

Participants :
- Institut d'Investigació Biomédica de Bellvitge (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet BIONICS (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Ischemic stroke occurs due to reduced perfusion to a brain region, because of the blockage of a blood vessel, resulting in death or permanent neurological deficits. It presents high percentages of mortality and morbidity worldwide and market analysis in five major EU countries showed that the total number of first-ever incidents of stroke cases will rise to 1.63 million (43.7% growth) by 2034. Although, many treatments that make use of therapeutic nanoparticles have been presented, unfortunately to date, no effective treatment has been found to prevent damage to the ischemic brain after stroke. Oxidative stress is related to the pathogenesis of stroke and overproduction of ROS and RNS are thought to be the main cause of this. In addition, the overproduction of MMP-9 has been related to many post-stroke side effects. Thus, I propose the development of a biomimetic and neuroprotective lipid nanocapsule (BIONICS) for the targeted treatment of post-stroke side effects. BIONICS will safely deliver anti-oxidant nanoparticles (CeO2) and iNOS inhibitors (L-NIL) across the BBB aiming at reducing the overproduced ROS, RNS and MMP-9, resulting in to the amelioration of the neurological deficits caused by oxidative stress. Through this project, the new skills in the synthesis of antioxidant nanocapsules, the use of molecular biology techniques, design and fabrication of microfluidic models, project management, grant writing, and other transferable skills that I will acquire in IIT, will help my future career plans providing knowledge and expertise in a field where my knowledge is limited. This action will also give me the opportunity to transfer my pre-gained knowledge through seminars/workshops to the institution where my research will be carried out. Overall, I believe that BIONICS will have a significant impact on my short and long-term career goals and will bring me one step closer to my impending goal of the independent researcher.

Mots clés : ischemic stroke, post stroke symptoms, neuroprotection, lipid nanocapsules, ceria nanoparticles, inos inhibitors, oxidative stress mmp9, in vitro, in vivo studies

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 168277.2 €
Projet MATHCOV (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

It has long been known that mother plants have a significant influence on progeny traits such as dormancy, seed size, and seedling growth vigour. Temperature is a highly influential environment factor on seeds, and can be sensed directly by either the mother plant or by developing seeds themselves, using an unknown mechanism to integrate temperature information over time. The endosperm plays an important role in the temperature regulation of dormancy, but and previously direct investigation of temperature-controlled events in the endosperm has been limited by the small seed size of the model species Arabidopsis. Here, I will investigate how temperature controls progeny dormancy and seedling growth vigour via endosperm in Brassica oleracea, a key vegetable species that contributes to human health and nutrition, using high resolution timeseries transcriptomics. Gene network and epigenetic profiles will be analysed dynamically and integrated for endosperm and embryo at different after temperature perturbations, to form a high resolution of early and late events that lead to temperature signals in seeds. This will enable the identification of key genes and stably-inherited epigenetic markers involved in temperature-induced differences in seed vigour difference. The resulting model will be tested in Arabidopsis and Brassica by knock-out mutant and transgenic experiments. This duel approach is an effective strategy to control risk. Avenues for the effective dissemination and exploitation of results will be developed by the fellow. Relevant training will be provided to during the fellowship. Ultimately, this project enable us to better understand seed vigour and could benefit seed companies, farmers and policy-makers by showing how to add resilience to environmental variation on seed performance.

Mots clés : seed vigour, temperature, network biology, epigenetic memory, brassica

Participants :
- UK Research and Innovation (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 195454.8 €