Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet Arterial Aging (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Cardiovascular disease (CVD) is the number one cause of death in Europe. Arterial dysfunction develops with aging making advancing age the primary risk factor for CVD. Advancing age can induce adverse changes in the gut microbiome, which in turn, can activate systemic pro-oxidant and pro-inflammatory signaling pathways with detrimental downstream consequences. One main objective of this project is to investigate the role of the gut microbiome in modulating arterial function with aging. To approach this objective, I will carry out two experimental studies: 1) mouse-to mouse transplant of gut microbiota to investigate if gut microbiota transfers vascular phenotypes. This experiment will show if gut microbiota modulates arterial function with aging, and will provide insight into the mechanisms involved. 2) Germ-free mice with microbiota samples from human subjects to determine the contribution of the human microbiome to a particular phenotype. Cetaceans are long-lived mammals and excellent divers. They undergo constant cycles of tissue hypoxia-reoxygenation and shear stress caused by vascular adjustments while diving. In humans, these adjustments produce an elevation of oxidative stress and inflammation markers and impairment of the endothelial function. Thus, another main objective of this proposal is to explore if cetaceans, i.e. whales and dolphins, have developed an endothelium-protective mechanism to prevent arterial dysfunction with age and diving. To approach this objective I will study vascular function, circulating oxidative stress and inflammation markers, and gut microbiome of cetaceans of different ages in captivity as well as stranded animals. The objectives to investigate the role of the gut microbiome in modulating arterial function with aging will be carried during the first two years in the outgoing phase. This knowledge will be transfer to the host institution for the study of vascular function and gut microbiome in cetaceans of different ages.

Mots clés : gut microbiota, arterial dysfunction, gut dysbiosis, arterial aging, germ free mice, cetaceans

Participants :
- University of Las Palmas de Gran Canaria (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 245732.16 €
- University of Colorado System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet PAELLA (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cardiovascular disease is the leading cause of death world-wide, affecting both men and women. Myocardial infarction and ischemic stroke are two severe consequences of cardiovascular disease caused by formation of an occlusive thrombus. Blood coagulation and thrombus formation is a complex interplay between clotting factors, platelets and endothelial cells lining the blood vessels that often involve interactions with leukocytes and other inflammatory cells. I propose to study a novel receptor on platelets, PEAR1, and its role in haemostasis, inflammation and thrombosis. I will use unique, synthetic poly-sulfated sugars that I have characterised as novel agents to activate PEAR1 and take advantage of the 30 years of experience of my host, Professor Watson, in studying platelet activation, and the recent identification (unpublished) of the natural ligand in the body which activates PEAR1. I will use state-of-the-art methodology available in Birmingham including flow chamber studies, CRISPR-CAS knock-down, phosphoproteomics, super-resolution and light sheet microscopy, intravital microscopy and a PEAR1 deficient mouse model to test my hypotheses that PEAR1 plays a critical role in thrombus stabilisation at sites of injury and drives thrombo-inflammatory disease in the vasculature. Uncovering the role of the novel receptor PEAR1 may lead to new treatment strategies to combat thrombosis.

Mots clés : pear1, platelet, endothelium, thrombosis, blood coagulation, inflammation, receptor signalling, glycopolymers, sulfated carbohydrates

Participants :
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet SODIUMMRI-4-EU (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Cardiovascular diseases (CVD) are the leading cause of death with 60% of CVDs associated with coronary artery diseases (CAD). CAD is the major cause of myocardial infarction (MI), commonly known as heart attack, which can be life threatening and places a huge socio-economic burden on the EU. The most widely used therapy for CAD is revascularization, and myocardial viability is a determining factor and predictor for patient outcomes. Magnetic resonance imaging (MRI) has become a mainstay of clinical diagnosis, but so far has seen limited use in the study of the heart. Here I aim to unlock the potential of myocardial viability imaging with physiometabolic MRI to provide a new instrument for the diagnosis and assessment of therapy success of CAD. Therefore I propose a quantitative approach based on MRI of sodium (23Na) that will allow me to observe new features of the working heart, at a level of resolution that will be highly valuable in understanding, finely diagnosing, and designing treatments for CVD. To meet this goal I pursue the development of cutting edge sodium MRI technology. Its capacity for quantitative assessment of sodium tissue content will be validated in model systems and in healthy subjects. The clinical applicability of 23Na MRI for viability imaging will be examined in revascularized MI patients. For this purpose I will leverage the sensitivity gain inherent to ultrahigh field MRI (B0≥7.0 T), capitalize on my outstanding expertise in the field of physiometabolic MRI and build on my interdisciplinary skills formed around MRI physics. In this project, this expertise will be taken to the next level to elucidate the progression of sodium concentration in ischemic myocardial tissue. This research will eliminate the main barriers to the study of tissue viability and will open entirely new possibilities for non-invasive, in vivo phenotyping as a tool for individualised medicine tailored to offset a major socio-economic burden on the EU induced by CVD.

Mots clés : tissue viability imaging, sodium magnetic resonance imaging, at ultra high field strength

Participants :
- Max Delbrück Center for Molecular Medicine (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 171460.8 €
Projet Magnetic HEART (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cardiovascular diseases are responsible for the greatest proportion of deaths in people under the age of 70 and cost the EU €110 billion each year. A major cause of heart dysfunction following myocardial infarction is the extensive remodeling of the extracellular matrix (ECM), which leads to the formation of fibrotic scar and death of cardiomyocytes - a collective process known as myocardial remodeling. Diagnosis and treatment of this progressive pathological remodeling process are a top priority in modern healthcare. The project aims to develop novel 3-dimensional (3D) human Magnetic HEART tissue based on unique magnetic nanoparticles (MNPs), and includes two world firsts: (1) a model for long-term live monitoring of ECM remodeling and (2) a new generation of scaffold-free myocardial regeneration techniques. Innovative MNPs will be designed and synthesized to target and specifically label human cardiomyocytes and human cardiac fibroblasts. By applying an external magnetic field, the magnetically labeled heart cells will be accumulated to produce 3D human cardiac tissue, comprising its own biologically-produced ECM, which will offer a practical alternative to native human heart tissue. For the first time, live biochemical changes in cardiac ECM during physiological and pathological remodeling will be monitored using state-of-the-art Raman spectroscopy, which can reveal fundamental insights and improve the basic understanding of this process. This platform, which has not previously been reported, can be translated to treat the remodeled area in the heart by restoring structure and function to the damaged heart tissue, and marks a major breakthrough in magnetic targeting therapy for lesions localized deeper in the body. The outcome of this research has the potential to impact health and society and become a vital component in therapeutic approaches to cardiovascular diseases.

Mots clés : myocardial remodeling, cardiac regenerative medicine, magnetite nanoparticles, extracellular matrix turnover, raman spectroscopy

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet MiNeMI (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cardiovascular diseases are the leading global cause of death, being ischemic heart disease one of the deadliest. To date, the conventional therapeutics only ameliorate the state of care of myocardial infarction (MI) patients, and no approved therapy has been developed for heart scars. Promising approaches might come based on the latest knowledge on new pathophysiological concepts, e.g. on the inflammation and immune responses upon MI. The inflammatory phase on MI presents itself as a therapeutic opportunity, with immunomodulation for heart regeneration showing great promise for MI treatment. Thereby, MiNeMI aims to answer the question if it is possible to modulate the immune system to regulate inflammation and promote heart regeneration through a non-invasive approach. To this end, MiNeMI will, for the first time, develop a novel and unique double-layer biodegradable non-invasive microneedle (MN)-assisted nanovector skin patch, loaded with both immunomodulatory and biologic (cytokines, proteins, and extracellular vesicles) cargos to be tested in a myocardial infarction (MI) disease model. The MN-patch approach proposed here will deliver the cargos into the dermal layer of the skin, a reservoir of immune cells, and will revolutionize the way to regulate the inflammatory systemic immune response upon cardiac ischemia. This MN-assisted nanovector skin patch will be fully characterized in vitro for immune and cardiac effects and also tested in animal MI disease models.

Mots clés : microneedles, immunotherapy, myocardial infarction, inflammation, nanoparticles, nanovectors, biomaterials

Participants :
- University of Helsinki (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 190680.96 €
Projet DANHIMC (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Catalytic hydrogenation reactions have many important applications in the synthesis of chemicals, pharmaceuticals, and fuels. However, currently most catalytic hydrogenation systems rely on catalysts that contain rare and precious late transition metals. [Fe]-hydrogenase is an enzyme considered as an efficient catalyst for hydrogenation reactions. Though various Fe-based synthetic mimics of the active site of [Fe]-hydrogenase have been synthesized, only one of them was reported to activate H2. Recent studies have revealed the great potential of Mn as hydrogenation catalysts. Here we propose to combine the active site of [Fe]-hydrogenase with Mn metal and develop a novel class of Mn complexes. Complex design and synthesis, structure-function study, hydrogenation methodology development and reconstitution of [Mn]-hydrogenase for biochemistry study are the main objectives of this proposal. This work will result in not only new fundamental understanding of base metal catalysis, but also industrially relevant catalysts.

Mots clés : biomimetic chemistry, fe hydrogenase, base metals, manganese, hydrogenation

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187419.6 €
Projet FCRE (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Causation is a basic feature of the structure of nature and thus in the centre of much research. Hitherto, however, the distinctive role and applicability of formal causation has been underappreciated. Formal causation is at play whenever a thing has a certain essential property because it is of a certain kind. E.g., that a particle has negative charge because it is an electron. Such kind-based explanations are ubiquitous across the sciences, and references to kinds are often indispensable. More controversially, such kind-based explanations point towards a specific variant of causation. During Formal Causation I (funded by DFG), I developed a mature theory of formal causation that would justify its applicability to contemporary metaphysics and philosophy of science. (1) I reconstructed Aristotle’s account, especially the non-hylomorphic variant with fewer ontological commitments found in his Posterior Analytics. (2) I applied the account of formal causation to topics of contemporary interest. Especially, (i) developed the non-modal account of essence such that it is able to deal with exceptions, (ii) discovered that in a case of formal causation the form is a full immediate ground, (iii) defended an account of laws of nature. Further work remains, both on the relation to possible rivals of formal causation, and on extensions. This project will investigate (1) Aristotle’s originally intended scope of the formal cause and his thoughts on the relations between the four causes distinguished by him; (2) the application of formal causation to occurrent entities like processes and events; (3) whether hylomorphic compounds can be thought of as mereological compounds of different parts, and if so what the relation to formal causation is; (4) whether formal causation should be thought of as a variety of downward causation and relate this to the debate about mechanistic explanations; and (5) formal causation as a type of metaphysical explanation.

Mots clés : aristotle, form, causation, essence, occurrants, processes, hylomorphism, downward causation, new mechanists, metaphysical explanation

Participants :
- University of Reading (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet MitoScaling (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cell division is a common process to all cell types in a multicellular organism. During mitosis, equal chromosome segregation in anaphase is regulated by an Aurora B phosphorylation gradient, centered at the midplane between the two chromosome sets. The gradient gives positional information that allows nuclear envelope reformation (NER) only when chromosomes are far enough from the kinase activity. Considering the 120μm human zygote and a 15μm fibroblast, how can the gradient scale with cell size over such wide range of sizes? To unravel the scaling mechanism, I will measure the biophysical parameters of this phosphorylation gradient using a FRET sensor and optogenetics to manipulate the gradient with fast spatiotemporal kinetics. I will address three key questions: i) Does the gradient sense cell size? ii) If so, how is size information used to scale the gradient? iii) How is gradient scaling translated into NER positioning? I will focus on three zebrafish cell systems with extreme sizes and dynamics: 1) embryonic cleavage divisions, where cell size halves with every cell division; 2) EVL cells, which are stretched quickly into flatter cell sizes, implying fast scaling dynamics; 3) asymmetric division in neuronal precursor cells, where the two sides of the spindle midzone must scale differently to generate daughters of different sizes. With this approach, I will generate unprecedented information on the regulation of anaphase chromosome separation in its natural context. This entry point in anaphase will provide a conceptual frame and a tool kit to address a more general problem: how do other mitotic machineries scale with cell size? A wider question for my long-term future research.

Mots clés : mitosis, gradient, scaling, cell size, vertebrate embryogenesis

Participants :
- University of Geneva (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187419.6 €
Projet Centromere Stability (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cell division relies on centromeres, which connect chromosomes to the spindle for separating sister chromatids in mitosis. Human centromeres are composed of large arrays of repetitive DNA, which are often sites of aberrant rearrangements in cancer. While centromere defects can cause chromosomal instability, the molecular mechanisms that maintain their repetitive DNA stable are poorly understood. During the fellowship, I aim to investigate how human centromere stability is maintained and the consequences of centromere dysfunction in driving cancer and aging. To circumvent impeding technical barriers due to incomplete centromere sequence annotation, I have ideated the use of Chromosome Orientation Fluorescence In Situ Hybridization at human centromeres (Cen-CO-FISH; Giunta, 2018). Using this innovative technique, I revealed that CENP-A and CCAN (constitutive centromere-associated network) proteins prevent centromere instability, and this functionality is compromised in cancer cell lines and in primary cells undergoing senescence (Giunta & Funabiki, 2017); my data show that CENP-A may play a new role during centromere replication, preventing DNA damage, repeats shortening, and subsequent aneuploidy. I will use the Auxin-Inducible Degron (AID) system and CRISPR-Cas genome editing with high-throughput imaging of Cen-CO-FISH to identify the human centromere maintenance network and investigate the mechanisms of repeats stability. I will also examine the consequences of centromeres dysfunction, including changes in the size of the array, cell ploidy and proliferation dynamics, using a variety of validated and novel methods, including Cen-qRT-PCR, qFISH and cytogenetic assays. Altogether, the proposed research will unveil a novel conceptual framework to explain the fragility of repetitive centromere DNA and its consequences on cell physiology and disease. This work will lay the foundation for my future independent research on centromere instability in age-associated cancers.

Mots clés : centromere, repetitive dna, genome stability, recombination, sister chromatid exchange, chromosome orientation fluorescence in situ hybridization  co fish, senescence, cancer, aging, aneuploidy

Participants :
- Sapienza University of Rome (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183473.28 €
Projet OPTIC BIOEM (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Cell membrane permeabilization, involving its reversible or irreversible restructuring, under extremely short electric (E) pulses exposure (from hundreds of us down to few ns) has a key role in a number of clinical, preclinical, and medical research applications. Hence, the knowledge of its bio-physical nature and dynamics (i.e. formation and resealing processes) is crucial for an aware control of delivered protocols, and for predicting treatments efficacy under established biological (e.g. buffer conductivity, cell dimensions) and electromagnetic (EM) conditions (e.g. pulse duration, amplitude, shape). To understand bio-physical mechanisms underlying such a pulse-exposure permeabilization, an innovative and advantageous approach is proposed based on real-time molecular vibrational modes imaging using fast Coherent anti-Stokes Raman Scattering (CARS) of in vitro samples under such a stimulation. Hence, in the present Marie Sklodowska Curie Action (MSCA), a fast CARS microscope will be integrated with a suitable wide band in vitro electromagnetic field (EMF) exposure setup to study the role of membrane lipid reactions and interfacial water in the electropermeabilization phenomenon. This innovative CARS analysis will be supported by mass spectroscopy measurements to verify the appearance of corresponding chemical species, and by simulated E field and pore density distributions on the bio-samples. This last step is an attempt to correlate sample areas presenting the highest CARS signal intensity with the correspondent E field and pore density distributions. The program that integrates engineering, physics, chemistry and biology will allow a substantial progression in my career and network ability through the work on a completely innovative, multidisciplinary and inter-disciplinary subject in one of the most reputed bioelectric laboratory, where the applications of electropermeabilization in biology and medicine where first developed in Europe and worldwide.

Mots clés : cars spectroscopy, extremely short pulsed electric field, broad band electromagnetic exposure device, cell membrane electropermeabilization, lipid peroxidation, microfluidics

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €