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

Heart disease is the most significant cause of morbidity and mortality in the industrialized world, and the cause of 4 million death each year within the European Union. The prevalence of the disease is a huge burden on society estimated to cost the EU economy 60 billion annually on drug therapy, patient care, and loss in productivity. Nonetheless, despite the latest advances in research much remains to be learn about pharmacological treatments in cardiovascular disease. Recently, the development of induced-pluripotent stem cells (iPSC) technology has led to the creation of ‘patient-in-a-dish” models through the utilization of iPSC-derived cardiomyocytes. In this setting, a high-throughput screening approach can applied to find novel therapeutic interventions and detect the cardiotoxicity of drugs. However, the limitation of the current format centers on the lack of phenotypic cardiomcyoytes maturity. Consequently, these in vitro models often fail to recapitulate relevant physiological traits. The aim of CAMEOS is to develop a cardiac microtissue with superior physiological relevance for in vitro high-throughput screening. I will employ state-of-the-art cardiac tissue engineering principles to improve the maturation of iPSC-cardiomyocyte. These will be scaled-down, by the development of microtissue, for utilization in high-throughput 96-well plate format, and will be validated by their pharmacological responses and iPS-disease modeling potential. I will apply the developed microtissue to model a complex disease mutation, phospholamban (PLN) R14del, for which the pathology is poorly understood and no cure is available. In the microtissue, I will be able to study the physiological implication of the mutation and perform a high-content screens in attempt to find novel therapeutic targets.

Mots clés : cardiac tissue engineering, high throughput screening, phospholamban, disease modeling, induced pluripotent stem cells, biomaterials

Participants :
- Stanford University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University Medical Center Utrecht (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 260929.8 €
- University of California System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet MACROVALVE (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Heart valve disease is predicted to be the next cardiac epidemic. Valve prostheses used to treat this disease are comprised of biological tissue. However, these bioprosthetic leaflets degrade, limiting their long-term efficacy. Macrophages have been found within explanted leaflets and are key determinants of biocompatible outcome. However, their role in bioprosthetic leaflet remodelling is poorly understood. Males and females for unknown reasons are also predisposed to calcific and fibrotic leaflet degeneration, respectively. MACROVALVE’s goal is to elucidate the contribution of macrophages to the fibro-calcific remodelling of bioprosthetic leaflets. First, the applicant will apply histological, multi-omics and network analyses to constitute an integrated multi-omics map of human bioprosthetic leaflet degeneration. The differential pathogenesis between male and female disease will be determined. The results will also be compared against data for native aortic valve disease at different stages: early-disease, fibrotic and calcified. Electron microscopy will be used to identify extracellular vesicles. Secondly, the discrete response of sex-separated macrophages in the presence of hormonal milieu and physiological stimulation will be investigated. Ultimately, the innovative application of these techniques to unravel the innate immune response to bioprosthetic replacements will pave the way for novel therapeutics to prolong leaflet lifespan. The project is in line with the Horizon 2020 focus area Health, Demographic Change and Wellbeing. The candidate will spend the first two years of this fellowship training in multi-omics and network analyses at Brigham and Women’s Hospital in the United States. She will transfer these skills to Ireland during the return phase and increase Europe’s reputation as a location of cutting-edge research. Through this fellowship, the applicant will reach a position of professional maturity required for success in her future career.

Mots clés : cardiovascular disease, medical device, bioprostheses

Participants :
- Mass General Brigham (Etats-Unis) — Partner, organization partner, Recherche, subvention : 0.0 €
- National University of Ireland (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 257561.28 €
Projet IMPROVING-GT (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) refers to the transfer of nucleic acids into HSPCs, to either add a new copy of a “healthy” gene or to correct a mutated gene. HSPC-GT is successfully used in clinic to treat patients with hematopoietic malignancies and several inherited diseases of the hematopoietic system. Yet, its current use is accompanied by acute conditioning-related toxicities, which impose a burden on patients and limit its application to the most severe conditions. HSPC-GT requires the following steps: HSPCs are mobilized and harvested from the patient, genetically corrected ex-vivo by gene transfer or gene editing and infused back to the patient, after administration of partial or fully myeloablative conditioning to make space in the bone marrow for the modified cells. Administered HSPCs home to the bone marrow, where they engraft and reconstitute a healthy immune system, theoretically throughout life. However, two major shortcomings undermine the full therapeutic potential of HSPC-GT: (i) a decrease in short- and/or long-term engraftment potential due to the ex vivo manipulation of HSPCs and (ii) a toxicity in the hematopoietic and non-hematopoietic organs related to the conditioning regimens, which are based on cytotoxic drugs. The project IMPROVING-GT proposes to develop innovative schemes to increase engraftment and dodge genotoxic conditioning, which are some of the most coveted but still unaccomplished goals of HSPC-GT. The candidate aims to (1) increase the fitness of genetically modified HSPCs by uncovering new players of engraftment and (2) bypass the toxic conditioning requirement by exploiting enhanced mobilization reagents. IMPROVING-GT will pave the way towards non or milder genotoxic regimens, which should greatly minimize undesirable toxicity of current treatments and ameliorate patients’ outcome. Moreover, it may help broadening applications of HSPC-GT to more diseases, including patients with lower disease burden.

Mots clés : gene therapy, hematopoietic stem cells, engraftment, transplantation, conditioning, gene editing, mobilization

Participants :
- Istituti di Ricovero e Cura a Carattere Scientifico (Italie) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 183473.28 €
Projet HIPShot (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Hepatitis B virus (HBV) is a major global health problem resulting in progressive liver disease, including cirrhosis and hepatocellular carcinoma – the second leading cause of cancer death worldwide. Although HBV structure and genome have been characterized, key aspects of the viral life cycle remain poorly understood because of the lack of a robust HBV infectious tissue culture system. Moreover, despite the development of a safe and efficient vaccine, over 240 million people are chronically infected with HBV. Thus, the development of efficient anti-viral strategies to cure HBV infection remains a critical unmet medical need. To date, there is an important gap of knowledge in basic HBV biology that results in the lack of identified drug targets to cure chronic HBV infection. These limitations can now be overcome using a state-of-the-art HBV tissue culture model combined with technological advances in genetics and proteomics. The aim of HIPShot (Hbv genetIc and Proteomic Screen) is to use cutting-edge screening techniques in human cells to identify host factors that are essential for HBV infection and at the same time targets for antiviral cure. With my expertise in using forward genetic screening and proteomic approaches, I decided to join one of the leading groups in HBV research, lead by Prof. Thomas Baumert (TB) and based at Inserm Unit U1110 of Université de Strasbourg (UdS), to exploit novel technologies in the investigation of host-virus interaction. The proposed project will provide unmatched insights into the basic biology of HBV infection by shedding new light on cellular host factors exploited by HBV to replicate and persist in human cells. These identified host factors will constitute direct drug targets with an important therapeutic potential.

Mots clés : drug target identification and validation

Participants :
- Université de Strasbourg (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 185076.0 €
Projet HEGEMONIC (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. Although several environmental factors have been identified, many affected individuals never develop HCC, suggesting a genetic susceptibility. Candidate genes and genome-wide association studies (GWAS) have only uncovered a few variants reproducibly linked to HCC. GWAS design typically allows the detection of common variants that usually have small effect sizes. Even taken together, they explain a very limited proportion of the heritability. This could reflect the presence of rare variants that may confer very large effect sizes. These may be captured by next-generation sequencing (NGS). Whole exome sequencing (WES) of thousands of tumors has defined the somatic genetic landscape of the most common cancers. Using WES, the host group has strongly contributed to the identification of the major pathways recurrently mutated in HCC. Nevertheless, despite the large amount of NGS data generated by cancer genome projects, the analysis of rare germline variants (i.e. variation pre-existing in normal cells) is currently a neglected field, particularly in liver carcinogenesis. The HEGEMONIC project hypothesizes that rare variants in coding regions of the genome (exome) impact the risk of HCC. This project proposes an integrative approach combining (epi)genomic information generated by the host group and from publicly available sources. First, the applicant will compare WES data from a series of 350 patients with HCC to nearly 70,000 controls compiled by the Exome Aggregation and UK10K consortia. Then, validation of the top signals will be performed by conventional sequencing in three replication cohorts. Finally, the applicant will analyze genotype-phenotype associations, taking advantage of the extensive clinical data available. Ultimately, the HEGEMONIC project may generate new biological hypotheses in liver carcinogenesis and identify new biomarkers and pharmaceutical targets.

Mots clés : liver cancer, exome sequencing

Participants :
- Université Paris Cité (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173076.0 €
Projet BRCAstem (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Heterozygous germ line mutations in the breast cancer susceptibility genes (BRCA) 1 or 2 predispose carriers to breast, ovarian, pancreatic and prostate cancers. Significant evidence has accumulated in recent years on vulnerabilities specific to BRCA1/2-deficient tumours, leading to the development of personalized therapies, such as poly-ADP ribose polymerase (PARP) inhibitors. However, tumours develop resistance to these therapies, with tumour heterogeneity and enrichment in cancer stem cell (CSC) sub-population as an underlying resistance mechanism. How the genomic instability intrinsic to BRCA1/2 inactivation impacts on CSC survival and propagation during tumorigenesis and their relevance to the response to therapy has not yet been established. Previous results obtained in the host laboratory show that BRCA2 loss is associated, in the long term (28 days after BRCA2 abrogation), with upregulation of genes involved in metastasis and CSC markers, suggesting BRCA2-deficient cells can acquire metastatic and tumour-initiating capacity. In the current project proposal, we intend to study at single-cell resolution the relationship between CSCs and the response to PARP inhibitors and ionizing radiation (IR) in cancer cell lines and patient-derived xenografts (PDXs) lacking BRCA2 . We will develop a combined single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) experimental approach to characterize BRCA2-deficient CSC subpopulations and to monitor the spatio-temporal dynamics of the CSC signature. This will enable us not only to understand the molecular mechanisms driving cell plasticity in models of BRCA2 inactivation, but also to evaluate the CSC impact on the response of BRCA-mutated tumours to current targeting therapies.

Mots clés : brca1 and brca2 genes, dna damage

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet REPROHEAT (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

High ambient temperatures represent an obstacle for reproductive development in plants. Our own preliminary data indicate that mutations affecting auxin methylation facilitate pollen tube growth and confer increased reproductive capacity under higher temperatures in the model plant Arabidopsis thaliana. We propose to explore the benefit of reducing auxin methylation in temperature-sensitive crops like tomato and rice to maintain higher fruit/grain yields under heat and drought stress conditions. The research program includes field testing of new tomato varieties generated in this project, in conjunction with a crop company. The combined approach using CRISPR/Cas9 genome editing technology and chemical genetics, together with the thorough training program that we have devised, is targeted at complementing Dr. Resentini’s strong experience in plant molecular and cellular biology. By the end of the term, she will have an advantageous professional position at the interphase between Academy and European Industry.

Mots clés : plant, temperature stress, plant hormone, tomato, reproductive development

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet ELISIR (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : SIGNED

High clouds play an important role in modulating Earth’s radiative balance by (i) reflecting shortwave radiation and (ii) preventing longwave radiation from escaping to space. These interactions with radiation also influence atmospheric circulation at all scales, from global to local. The temperature and height response of high clouds is well understood, but changes in their extent, optical depth and ice properties including ice water content, ice crystal number, and ice crystal size remain uncertain. Ice properties are important because they determine cloud radiative effects and lifetime. However, many climate models cannot interactively simulate ice crystal number and size because they use simple 1-moment microphysical schemes with ice crystal mass as the only prognostic cloud ice variable. The proposed project ELISIR will study the role of ice crystal size and number for high cloud feedbacks and dynamical responses and compare results from 1-moment with more advanced 2-moment cloud microphysical schemes, in which also ice crystal number is a prognostic variable. We hypothesize that a direct link exists between the upper tropospheric stability and the number of nucleated ice crystals, which may lead to changes in cloud optical properties and lifetime, with a significant impact on climate. The research aims will be achieved with the help of global climate model simulations and high resolution limited-domain simulations in a tropical domain, whereby each simulation will be performed once with a 1-moment and once with a 2-moment microphysical scheme. Furthermore, the CMIP6 archive will be analysed to test whether there are systematic differences in simulated cloud radiative effects between models using 1-moment and models using 2-moment microphysical schemes. This will help to better understand the drivers of high cloud feedbacks and therefore to narrow estimates of Earth’s climate sensitivity and uncertainties in the high cloud impact on the atmospheric circulation.

Mots clés : high clouds, cloud feedbacks, cloud microphysics, anvil clouds, climate dynamics, climate modelling

Participants :
- University of Vienna (Autriche) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 174167.04 €
Projet NP-SPAD (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

High efficiency detection of single photons at telecommunication wavelengths (notably at 1.55 µm) is critical for emerging technologies, such as free-space and on-fiber quantum information processing, eye-safe and long-distance light detection and ranging (LiDAR), and highly sensitive remote sensing. This research project aims to meet this critical need by developing III-V nanopillar-based uncooled single-photon avalanche diodes (NP-SPADs), which are composed of nanostructured InAsP-InP Geiger-mode avalanche photodiodes (GmAPDs) with self-assembled plasmonic gratings, operating at 1.55 µm. Compared with commercially available InGaAs(P)-InP GmAPDs, the proposed device scheme significantly suppresses thermally generated carriers and trap state population by a factor of 20 to 100 due to the extremely small fill factor of nanopillar arrays (less than 5%). All the while, sufficient optical absorption is maintained via surface plasmon resonance by the plasmonic gratings. The sum combination of these unique capabilities offers the promise of achieving NP-SPADs with free-running mode operation, high photon detection efficiency (PDE; probability of detecting a single photon) of 10 – 20%, low dark count rate (DCR; rate of false detection) of ~50 Hz, and high photon count rate ≥5 MHz. If successful, this approach can drastically stimulate the development and commercialization of high performance semiconductor-based NP-SPADs, putting European Union (EU) at the forefront of cutting-edge technology in single photon detection.

Mots clés : nanowires, inasp inp, single photon detection, avalanche photodiodes, near infrared, free running mode, plasmonic gratings

Participants :
- Cardiff University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet Exa-FireFlows (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

High performance computing (HPC) has transformed scientific research across numerous disciplines by supporting theory and experiments with numerical simulations. Exascale computing is the next milestone in HPC and is called to play an important role in economic competitiveness, societal challenges and science leadership. Combustion is one of the fields with high strategic importance and potential to fully exploit the future exascale systems. Nowadays, combustion of fossil fuels is the main power source, and some projections indicate that the combustion of liquid fuels will still dominate transportation and power generation industries for the next 50 years. Further understanding of the physics and chemistry of the combustion process is fundamental to achieve improvements in fuel efficiency, reducing greenhouse gas emissions and pollutants, while transitioning to alternative fuels and greener technologies. The use of advanced numerical simulations has enabled to make important contributions for increasing cycle efficiency, reduction of pollutant emissions, and use of alternative fuels in practical applications. The exascale computing will enable the development of high-fidelity turbulent combustion simulations that could not be analyzed before because it was too computationally expensive. However, the implementation of the new and future supercomputers require the evolution of multiple and different technologies in a coherent and complimentary way, including hardware, software, and application algorithms. Scientific codes and formulations need to be re-designed and adapted in order to exploit the different levels of parallelism and complex memory hierarchies of the new and future heterogeneous systems. The goal of the project is to explore and develop novel co-execution, memory awareness and communication avoidance strategies into a framework that allows the simulation of advance high-fidelity multiphase reacting flows in complex geometries using unstructured grids.

Mots clés : exascale computing, high fidelity simulations, heterogeneous computing

Participants :
- Barcelona Supercomputing Center (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €