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

Carbon sink conservation is a priority under the current Global Change scenario. However, our understanding of the factors that threaten natural carbon-storage systems is limited by the paucity of long-term records capturing their responses to anthropogenic- and climate-driven perturbations. Much of this limitation arises from the short time span covered by ecological monitoring, usually going back just a few decades at best. To capture decadal-to-millennial scale dynamics, an alternative approach is to use the palaeoecological record. Here, I propose a multiproxy palaeoecological approach to study the long-term resilience of two paradigmatic terrestrial and marine carbon sinks: peatlands and seagrass meadows. I will monitor changes in biodiversity and carbon storage ability using a state-of-the-art, multidisciplinary combination of palynology and charcoal analysis, dating by lead and carbon isotopes, sedimentology, geochemistry and numerical methods. Integrating these complementary proxies, I will reconstruct millennial-long ecological dynamics (e.g. long-term trends and regime shifts) to evaluate the effect of human and climate impacts on carbon sinks’ ecosystem services. This knowledge will inform conservation priorities by identifying the most influential drivers of ecological change. Moreover, it will propose conservation targets by reconstructing pre-anthropogenic ecosystem states. To increase its translatable impact, PALAEOCON will focus on Iberian habitats that are protected under the Habitats Directive of the European Commission. Indeed, I am committed to engaging with environmental authorities to complement current conservation strategies. On a broader scale, PALAEOCON will produce high-resolution, multiproxy records on the Holocene palaeoenvironmental history of southwestern Europe. By offering valuable insight to both applied and basic science, PALAEOCON will help advance my career aspiration of establishing as a world-class leader in palaeoecology.

Mots clés : peatlands, seagrass meadows, multiproxy approach, palynology, charcoal analysis, geochemistry, sedimentology, anthropogenic impact, holocene

Participants :
- University of Santiago de Compostela (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 241398.72 €
Projet MetEpiC (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Carcinogenesis is a multi-factorial disease which combines genetic mutations, aberrant epigenetic landscape and altered cell metabolism. TP53 which is the most mutated gene in human cancers, is known to regulate cell metabolism. It has been recently established that the metabolic status of cells can modulate the epigenetic landscape. The goal of this proposal is to characterize metabolic-driven modulation of epigenetic landscape during carcinogenesis using TP53 mutated cancers as models. In this project, we plan to address how TP53 mutations alter cell metabolism and the epigenome, thus creating abnormal gene expression facilitating carcinogenesis. Thanks to our preliminary data we will focus our attention on Acetyl-CoA metabolism and histone acetylations. This project will take advantage of state-of-the art approaches such as metabolomics, epigenomics and transcriptomics. My expertise on epigenetics and metabolism, as well as the expertise of the supervisor in the field of TP53 and carcinogenesis, are major assets for this project. Altogether, we expect that unraveling novel mechanisms interconnecting TP53 mutations, cellular metabolism and epigenome will provide new insights for understanding cancer development. Moreover, we expect to propose innovative strategies to tackle cancers harboring mutated TP53 thanks to combination of drugs targeting metabolism and the epigenome. This fellowship will definitively help me to conduct a unique and promising research line in the European Community with the final goal to establish myself as an independent scientist.

Mots clés : epigenetics, histone acetylation, metabolism, acetyl coa, cancer, p53 mutations, transcription, oncogenesis, drug

Participants :
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 196707.84 €
Projet DTI4micro (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Cardiac Ventricular Remodelling (VR), i.e. the alteration of tissue microstructure that is a hallmark of several cardiac diseases, can have profound effects on cardiac function. A novel imaging technique, Diffusion Tensor Imaging (DTI) offers the potential to quantify VR in vivo and could thus have a significant impact on the assessment and treatment of cardiac disease. This project proposes the development of advanced analytical tools to evaluate its usability in the quantitative characterization of cardiac microstructure. The tools developed will aim at a) providing a mathematical description of normality in cardiac microstructure; and b) analysing local variation as an alternative descriptor for remodelling. A combination of preclinical and clinical validation will be performed, with histological slices used as ground truth for the identification of microstructural features. Emphasis will be placed on the development and application of a rigorous mathematical framework for the processing of tensor fields, including the quantification of local differences between tensors and the construction of statistical models for the quantification of pathology. The project joins an early researcher with extensive expertise in the statistical analysis of manifold-value data and its uses in medical imaging with an internationally recognized group in the analysis of cardiac microstructure and its links to electromechanical function. The host group has a network of collaborators including all relevant areas, from MRI physics to cardiac physiology. The program also includes the provision of further training opportunities for the applicant in different aspects from student supervision to preparation of research proposals, representing a unique opportunity for his development as an independent researcher.

Mots clés : diffusion tensor imaging, cardiac magnetic resonance imaging, cardiac microstructure, cardiac atlas

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet ROCKSOFT (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cardiac fibrosis is a major cause of diastolic heart failure, a condition affecting millions of people worldwide. Treatment is currently lacking, reflecting a lack of understanding of cardiac fibroblast physiology, the main cell type responsible for extracellular matrix (ECM) production and development of fibrosis. Mechanical stress activates cardiac fibroblasts causing differentiation into myofibroblasts with excessive production of ECM. I previously showed that syndecan-4 (SDC4) is essential for myofibroblast differentiation in response to mechanical stress, although the exact mechanism was not fully elucidated. SDC4 regulates Rho GTPases and Ca2+ influx through TRPC7 channels, previously suggested to be stretch-activated. Thus, we hypothesize that SDC4-dependent Ca2+ signalling and Rho GTPase activation are crucial for translating mechanical stress into pro-fibrotic fibroblast activity. Despite having Ca2+ binding properties on the extracellular part, no studies have examined the role of SDC4 in regulating extracellular Ca2+ distribution and dynamics. Based on preliminary data, we here introduce the novel concept of extracellular Ca2+ microdomains that are created and maintained by SDC4. These microdomains are conceivably affected by changes in cell contraction and actin cytoskeleton organisation, thus promoting fibrotic remodelling of the heart in response to aberrant Rho GTPase signalling in the fibroblasts. To investigate these hypotheses in cardiac fibroblasts, I have developed a novel in vitro model that combines stiffness and stretch to induce myofibroblast differentiation, and study the process using state-of-the art CRISPR gene editing. The expertise of Prof. Cord Brakebusch in Rho GTPase function and CRISPR combined with my expertise in SDC4 mechanotransduction in cardiac fibroblasts will substantiate the success of this project, potential discovery of novel therapeutic targets and the possibility for me to create an impactful research group profile.

Mots clés : mechanotransduction, cardiac fibroblasts, myofibroblasts, fibrosis, heart failure, syndecan 4, rho gtpases, mechanical stress, calcium

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212194.8 €
Projet STEMCELLTRACK (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Cardiosphere-derived stem cell (CDC) therapy for myocardial infarction (MI) has been shown to elicit moderate beneficial effects. Research currently focuses on improving CDC administration, retention and efficacy. This proposal aims to develop Magnetic Resonance Imaging (MRI) and engineering tools to facilitate this research. Specifically, microinjection of fluorine-19 labeled CDCs will allow for MRI tracking and quantification in vivo. Non-invasive global and regional cardiac function measurements will assess efficacy of stem cell (SC) therapy. Parallel to these studies will be an independent design, synthesis, use and evaluation of fiber-enriched scaffold. The anticipated impact will be multifaceted, including the study of cardiac function in disease, and the potential applicability of generated results with cutting edge SC regenerative technologies in heart failure and prominent cardiomyopathies. Research efforts will be stimulated in manufacturing processes for scaffolds, cardiac functional assessment post-injection of SCs, and validation of their homing, engraftment and viability using cellular tracking methods. Through a personalized career developments plan, the fellowship will allow training of the researcher in advanced cellular characterization, labeling, and bio-imaging techniques, synergistically with trans-European mobility, reinforcing his scientific, managerial and leadership qualities. Overall, the short-term objective is the advancement of the researcher’s career in science and the broadening of his scientific horizons. The long-term objective is to establish the researcher as an independent investigator, advancing the field as a chair of a Biomedical Engineering Department.

Mots clés : magnetic resonance imaging, stem cell biology, cellular tracking, biomedical imaging

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet SBCVD (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cardiovascular disease (CVD) is the leading cause of global morbidity and mortality. While psychological stress is a known cardiovascular risk factor, the mechanism by which the brain translates stress into CVD is poorly understood. The underlying cause of CVD is a chronic inflammatory disease called atherosclerosis, the progression and exacerbation of which have been strongly associated with the immune system, including B cells. B cells perform many functions including production of antibodies that provide immunity against disease and cytokines that modulate leukocyte function. However, it remains unknown whether B cells mediate the effects of stress on CVD. Recent studies from Prof. Filip Swirski’s lab show that stress profoundly affects the number and distribution of B cells in the body via a mechanism dependent on the activation of the hypothalamic-pituitary-adrenal axis. In this proposal, I will test the hypothesis that stress aggravates atherosclerosis by modulating B cell function. To recapitulate stress, I will employ a combination of optogenetic and chemogenetic approaches available in the Swirski lab to target specific regions in the brain and characterize the subsequent impact on the phenotype and functional diversity of B cells. I will then identify the B cell-specific mechanisms that mediate the effects of stress on the progression of CVD in Prof. Christoph Binder’s lab, thus facilitating the transfer of knowledge between USA and Europe. With the combined complementary expertise of the two labs, this project will be the first demonstration of the use of state-of-the-art neurological tools to address cardio-immunological questions with a systems biological approach. This approach will not only delineate potential therapeutic targets for immunomodulation of B cells in preventing and treating CVD, but will also provide a direct mechanistic link between stress and chronic inflammation, a general concept with implications beyond atherosclerosis.

Mots clés : psychological stress, atherosclerosis, b cell function, optogenetics, chemogenetics

Participants :
- Medical University of Vienna (Autriche) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 270349.44 €
- Mount Sinai Health System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet PolyBiota (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Cardiovascular disease (CVD) is the main cause of mortality in Europe with an annual estimated cost of €210 billion. Different European Public Health strategies have targeted diet to prevent/treat CVDs. This multidisciplinary and multi-institutional project aims to provide new insights into the role of the gut microbiota as a key player in the beneficial effects against CVDs associated with the consumption of Polyphenols (PPs)-rich foods. PolyBiota will be developed through innovative research at one of the epicenters of PPs research (CEBAS-CSIC) and secondment at FISABIO (Valencia, Spain). Epidemiological, clinical, and preclinical studies suggest that the consumption of PPs-containing food protects against CVDs (i.e, modulating angiogenesis in atherosclerotic plaques) . However, these benefits are not always observed due to the high inter-individual variability. The gut microbiota has emerged as an essential player that regulates the bioactivity of PPs. Recent clinical trials indicate that the gut microbiota composition play a critical role in the activity of PPs improving CV biomarkers. These studies open a new door to investigate how the interaction PPs-gut microbiota can modulate mechanisms associated with the improvement of CVDs. PolyBiota will investigate: i) role of the gut microbiota as mediator of the effects of the consumption of Ellagitannins (ETs)-/urolithin (Uro)-A- and Isoflavones (IsoFlv)-/equol-enriched diets on angiogenesis/mechanisms related in untreated and antibiotic-treated animals, ii) the “prebiotic-like effect” of the ETs, Uro-A, IsoFlv and equol consumption on the gut microbiota population, iii) the effects of the gut microbiota-biosynthesized messenguers or the ETs- and IsoFlv-derived metabolites on in vitro tubulogenesis. PolyBiota shows an innovative approach combining cutting-edge techniques, “big data” management, endothelial cells, and in vivo animal models providing a holistic scene of the Diet-Gut Microbiota-Host interaction.

Mots clés : diet, polyphenols, ellagitannins, urolithins, isoflavones, angiogenesis, cardiovascular diseases, microbiota

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet Upbiosens (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The Upbiosens project describes a novel method to produce water-dispersible and stable DNA-capped upconversion nanoparticles (UCNPs), keeping intact (or enhancing) the properties of both DNA and UCNPs. The UCNP@DNA nanohybrid will be able to detect the complementary target miRNA or DNA sequence. This detection will be based on the UCNP emission changes after NIR excitation in the presence of the fluorophore target RNA/DNA sequence. The hybridization will enable FRET from the UCNP to the fluorophore upon NIR irradiation, which will allow the quantitative measurement of nucleic acid. In addition, this new strategy for DNA functionalization of UCNPs will enable the control of the UCNP size during the functionalization step as well as the distance between UCNP and the energy acceptor. Both issues are critical for the design of novel, rapid, highly selective and sensitive FRET-based biosensors. This approach will be demonstrated for wo different compositions of UCNPs, NaYF4: Yb, Er (excitation at 980 nm) and NaYF4: Yb, Nd, Er (excitation at 800 nm) in order to enhance optical properties. The excitation at 800 nm reduces the overheating of biosamples due to the light absorption by water. Taking into account the exceptional UCNPs emissive properties, the capability for in vitro nucleic acid imaging of the nanobiosensor will also be evaluated. To our knowledge, the combination of a nucleic acid sensing and imaging using UCNP-based nanohybrids has not yet been attempted. This dual NIR NA biosensor/bioimaging nanohybrid can be promisingly bio-implemented, such as in prognosis, diagnostics and treatment of diseases, gene therapy, or forensic analysis.

Mots clés : upconverting nanoparticles, fret, surface chemistry, biosensors, bioimaging, mirna

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 185076.0 €
Projet PINK (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

The WHO defines Intimate Partner Violence (IPV) as any behavior within an intimate relationship that causes physical, psychological, or sexual harm to those in that relationship. IPV claims millions of victims worldwide, and women are by far most deeply affected. IPV poses unique challenges: it often goes undetected outside of the family unit and remains hard to treat due to its complex interpersonal nature. This evidence calls for better prevention, early screening, and interventions. Deepening our grasp of the deep wounds inflicted by IPV to the woman's heart and brain would help in achieving these unmet milestones. Multiple threads knit together estrogens and brain-derived neurotrophic factor (BDNF), a neurotrophin that, via the TrkB receptor, governs brain and heart well-being. Estrogen replacement increases BDNF expression in brain regions of ovariectomized mice, and the deletion of bdnf in the forebrain induces anxiety/depression in female mice. Here, I will test whether perpetuated IPV alters estrogen levels in premenopausal subjects, impairing BDNF/TrkB signaling, triggering cerebral/cardiac dysfunction, and interrupting the information flow between heart and brain. To test that, and the benefits eventually afforded by selective TrkB stimulation, or social enrichment (that boosts BDNF in the hippocampus), I built a mouse model of IPV morphed from the resident-intruder test: a highly aggressive male and a socially-defeated female. Strengthened by a cadre of collaborators expert in Neuroscience, Endocrinology, Cardiology, and Epidemiology, I seek to shed a mechanistic light on the brain/cardiac “wounds” inflicted by IPV on women, proposing some unprecedented remedies to prevent the transition from early alterations to overt heart, or brain disorders, or both. A better mechanistic understanding of the impact of IPV on women may help to maximize screening, intervention and prevention of IPV at the individual, interpersonal, and societal level.

Mots clés : intimate partner violence, stress, bdnf, estrogens, diastolic dysfunction, anxiety, brain heart axis

Participants :
- University of Padua (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171473.28 €
Projet ClusterDynamics (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

The ability of catalysts to facilitate chemical reactions and to make them selective is of immense importance for industrial production processes. A wide range of heterogeneous catalysts consists of supported active nanoparticles that are intrinsically metastable due to their high surface area. In order to fine-tune catalysts for maximum reactivity and selectivity, a key challenge is the fundamental understanding of particle mobility under reaction conditions. Despite decades of research, these cluster dynamics are still far from being well understood at the atomic scale. Project "ClusterDynamics" aims at investigating model catalysts with an unprecedented degree of definition, in particular size-selected metal clusters soft-landed on inert substrates by use of a laser evaportion cluster source. State-of-the art fast scanning tunnelling microscopy (FastSTM) will be used to monitor cluster diffusion and rearrangement on the atomic scale with a time resolution down to some ms. In particular, Pd clusters, which are a very versatile model system thanks to their rich redox chemistry, will be deposited on Moiré films, such as graphene grown on Ru(0001) or Rh(111) or boron nitride grown on Rh(111), and their dynamics monitored in real-time. Initially, thermally induced lateral diffusion as well as cluster-internal fluctuation will be studied in ultra-high vacuum conditions. Subsequently, it will be determined whether the cluster dynamics are influenced by the presence of adsorbate molecules and whether the adsorbate-cluster interaction is dependent on cluster size. Finally, the cluster dynamics will be studied under reaction conditions. In order to expose the clusters to a high pressure environment, a sniffer tube will be installed that can be brought into contact with the sample to introduce a gas environment. The influence of the ambient can thus be investigated by comparing the cluster dynamics before and after exposure to reactive gas atmospheres.


Participants :
- Technical University of Munich (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €