Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet PCAPIP (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

As a result of it’s specialized secretory functions, the prostate has a unique biology that makes it prone to the development of cancer. Specifically, a strong dependence on hormonal stimulation through the androgen receptor (AR) pathway that is implicated in driving downstream changes to the central metabolism of the cell. To find answers to clinical questions, I am delving into the fundamental mechanisms of a previously overlooked family of lipid kinases. The type II phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks) are responsible for regulating a proportion of phospholipid species found embedded in the membranes of various cellular organelles. Intricate differences of the composition of these membranes can have a major effect on the regulation of cell cycle, metabolite trafficking, growth and survival. Herein, I outline a basic examination of the PI5P4Ks that will establish the first understanding of their phenotypic importance in prostate cells. There is reason to believe that these enzymes are critical regulators of the AR pathway that may be a trafficking conduit for changes to AR regulated metabolites. To test this, I am generating the first prostate-specific PI5P4K knock-out mouse model. A state-of-the-art metabolomic evaluation of both this animal model and a collection of human cell models will uncover the ultimate relevance of the PI5P4Ks in prostate biology. The proposed study will provide valuable insights into a non-canonical family of kinases that could lay the groundwork their development as novel drug targets.

Mots clés : prostate biology and cancer, mouse model, kinase, androgen signaling

Participants :
- University of Bern (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175419.6 €
Projet BioMedBC (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

BioMedBC Proposal is focused on improving the patient management of Bladder Cancer (BC). BC presents with the highest recurrence rate and the highest associated costs of all cancers. Due to the intrinsic heterogeneity, the investigated drugs in clinical trials, cannot be easily introduced in the clinical practice. Molecular profiles/ biomarkers (BM) with predictive potential are required to enable patient stratification. The BioMedBC proposal aims at the application of systems biology and cross-omics data integration methodologies to achieve: a) the molecular characterization of BC and b) develop signatures to predict the clinical outcome. To achieve these goals, integration of: i) high resolution proteomics datasets (planned to be acquired within BioMedBC), ii) existing datasets that were obtained in previous EU collaborative projects and iii) publicly available transcriptomics data, will be conducted, focusing on the molecular characterization of BC. Emphasis is given on the investigation of disease prognosis. For this purpose, clinical and follow-up data, available from ongoing prospective studies (n=1758), will be utilized for correlation analysis of the molecular profiles/ biomarkers with disease outcome (recurrence, progression and survival). The prognostic value will be confirmed in newly collected samples with emphasis placed on urinary protein/ peptide profiles, as non-invasive urinary markers is of significant added value. The innovation is held on the prognostic BM that can be further used to stratify patients to those that could be benefited by a potential intervention and guide personalized therapy to improve BC patient management. In parallel, BioMedBC aims at expanding upon the current training of the ER, Dr. Maria Frantzi, on transferability of the basic research results to clinically useful products and create strong career prospects for her desired development as an owner of a future SME.

Mots clés : omics, systems biology, proteomics, bladder cancer, prognosis

Participants :
- Mosaiques Diagnostics and Therapeutics (Germany) (Allemagne) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 159460.8 €
Projet PATCHES (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Biocompatibility of medical implants and devices is of paramount importance for their safety, effectiveness, and utility. The release of medical devices that are not biocompatible and biodurable is still an issue (for instance, more than 100.000 European patients are implanted with Metal-on-Metal hip joints which have been found toxic under specific circumstances), which has recently resulted in a proposal of the European Commission for the amendment of the Medical Device Directive. Biocompatible materials should be assessed based on their chemical, physical and toxicological properties as well as on their interaction with body fluids. A rapid adsorption of proteins on the foreign material will favour the anchorage of the cells, leading to safer and more durable medical implants/devices. Proteins adsorption is influenced by chemical and molecular structure characteristics and by the distribution of electric charges at the interface between surface and proteins. The distribution of surface charge has been so far attributed to the chemical reactions of the surfaces with body fluids. However, other aspects such as contact conditions and relative motions of surfaces have been recently appointed as crucial factors in the distribution of charge on the surface and thus on protein adsorptions. The proposed project will focus on the analysis of tribologically induced surface charge distribution on different biocompatible materials and on its impact on protein adsorption. This research will be conducted using Density Functional Theory (DFT) calculations and classical Molecular Dynamics (MD) simulation methods and the models will be validated by experimental tests. The project’s main goal is the design of a multi-scale hybrid computation/experimental methodology that will allow to assess biocompatibility and pave the way to the future creation of novel biocompatible materials for both implant and nanomedical devices.

Mots clés : tribocharging, biomaterials, molecular dynamics simulations, surface charge analysis

Participants :
- University of Modena and Reggio Emilia (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 168277.2 €
Projet Meta-Origami (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Biodiesel production is usually accompanied by the production of 10% (w/v) glycerol as main low-value by-product, making it not yet economically competitive to petroleum-based processes. Recently, Ustilaginaceae fungi have attracted more attention due to their abilities of using crude glycerol to produce chemicals of industrial interest. Unlike established filamentous fungi, many Ustilaginaceae strains can grow in haploid and unicellular form, which are remarkably advantageous for industrial applications. Of note, U. trichophora was reported to have the highest titre for microbial malate production, even if the yield is still low. If the carbon lost during cultivation is suppressed, U. trichophora will be a novel candidate for industrial malate production and contribute directly to crude glycerol valorisation. However, the metabolic network and its function are not described for any Ustilaginaceae species. Isotope-assisted metabolomics approaches are powerful in exploring the metabolic network operation. By capturing the snapshot or the kinetics of metabolite pools, these approaches can guide metabolic engineering strategies to alter metabolic flux distribution and maximize target compound production. Therefore, this study aims to decipher the structure and dynamics of the metabolic networks of U. trichophora by using isotope-assisted metabolomics approaches. Results obtained in this research will guide ongoing efforts in metabolic engineering to maximize malate production from crude glycerol of U. trichophora. Further contributions will be made beyond the envisaged industrial applications, as the Ustilaginaceae are also investigated in the context of host-pathogen interactions and fundamental cell biology.

Mots clés : metabolic engineering, isotope assisted metabolomics, ustilago trichophora, glycerol, malic acid

Participants :
- RWTH Aachen University (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 159460.8 €
Projet NoBios (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Biofilms consist of bacteria, proteins and cells which attached to a solid surface. Prevention of biofilms is of extreme relevance in industry and science as they are ubiquitous and able to provoke corrosion or failure in pipelines, heat exchangers, biomedical devices, artificial implants or food processing facilities. Biofilms are often battled with antibiotics, but bacterial resistance is a major problem. Therefore, novel approaches are required to avoid biofouling. We will explore the application of (1) superamphiphobic coatings, (2) slippery liquid infused porous surfaces and (3) functional pillar arrays surfaces to battle biofouling. These surfaces have in common that they strongly repel water, blood and organic liquids, and even soap-water mixtures due to a synergy between rough topography and a special chemistry. We will monitor and characterize the adhesion of bacteria, proteins and cells to these surfaces depended on shape, size and chemical of composition of the surface and the liquids. Several classical and highly advanced cutting edge methods will be used to investigate the wetting and fouling properties of these surfaces, especially laser scanning confocal microscopy. In the final steps of the research, we will evaluate the robustness of the surfaces and the biocompatibility in order to establish potential real applications in collaboration with industrial partners. We exert a high impact of this fellowship to the scientific community and the rest of society.

Mots clés : bacteria, proteins, adhesion, adsorption, superhydrophobicity, superamphiphobicity, slippery surfaces, pillar arrays, laser scanning confocal microscopy, wetting, colloids

Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €
Projet DisCharge (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Biological molecular recognition is centred around the structure-function paradigm, involving interfacial complementary shapes and non-covalent forces. Intrinsically disordered proteins (IDPs), constituting up to 40% of the proteome, evade the structure-function paradigm, owing to their lack of persistent structure. Despite some IDPs forming folded complexes, numerous IDPs form disordered complexes stabilized by multivalent interactions. An extreme example is the recently discovered disordered high-affinity complex formed by two highly charged IDPs, the nucleosome binding linker histone (H1) and its nuclear chaperone prothymosin-alpha (ProTa), both key regulators of chromatin-structure and -function. IDPs are also often implicated in liquid-liquid phase separation (LLPS) driven assemblies that facilitate numerous biochemical interactions. The specificity question in IDPs becomes particularly pertinent for such charge driven disordered interactions and associated LLPS processes considering the great abundance of such highly charged disordered stretches in our proteome. Specific physiological function of most IDP interactions and associated LLPS processes imply an important role of specificity, albeit encoded differently from folded proteins. Only a multidisciplinary study spanning several complexity regimes, which is currently lacking, can uncover such altered specificity. I hypothesize that physiologically, ProTa/H1 interaction plays out in LLPS-driven heterochromatin assemblies leading to transcriptional regulation. I will probe ProTa/H1 interactions and phase behaviour with a set of systematically designed variants in incrementally complex milieu, from the test-tube to the cell, to reveal how the sequence dictates interactions and phase behaviour in-vitro and attribute a given function in-cell. This will shed light on specificity determinants of interaction and function for such highly charged IDPs.

Mots clés : idp interaction specificity, phase separation, sequence dynamics function relationship, linker histone chaperoning, transcription regulation

Participants :
- University of Zurich (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191149.44 €
Projet USOME (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Biological vesicles hold great promise as nano compartments for various applications such as drug delivery systems, therapeutics, and diagnostic tools but fundamental relationships between material properties and activity are not sufficiently understood to create new products for the benefits of the European society. The overall aim of USOME is to develop characterization approaches for these novel materials enabling proper functionalisation. In particular, this proposal focuses on the development of an entirely novel analytical approach for the analysis of emerging biohybrid vesicles. As model systems we indicate polymersome-hybrids and exosome-hybrids, representing a variation in structure in terms of stability, origin (synthetic/natural) and their hybrid counterparts (proteins/synthetic polymers). Two processes will be studied in detail (i) the encapsulation of proteins in polymersomes; and (ii) the modification of exosomes with proteins and polymers. As a result, advanced analytical methods for characterization of polymersome and exosome hybrids for potential application in therapeutics and diagnostics will be established. The key to this envisaged breakthrough is based on field flow fractionation technique coupled to multiple detectors for elucidation of the structural and compositional distributions in the biohybid systems. This highly topical research will be performed within the individual fellowship of a young, very talented, and curiosity-driven African researcher in a leading European research institute. The combination of his expertise in analytical techniques, the biohybrids formation knowledge of IPF and specific knowledge of the associated partners will enable significant scientific progress in the field and unlocks value for patients. Excellent, customized training will open the ER the doors to a unique research profile, fully embedded in the international scientific community and with outstanding career chances at the fronteers of research.

Mots clés : biohybrids, polymersomes, exosomes

Participants :
- Leibniz Association (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 162806.4 €
Projet BAYESLAND (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Biologists have sought to understand geographic patterns of species distribution for centuries. The process of community assembly, which determines how species integrate and maintain in local assemblages, is key to understanding the factors underlying species distribution. However, the extreme complexity of ecosystems has prevented the development of a general theory of biogeography and community ecology. This is exemplified by the current schism between ecological and historical biogeography. Historically, short-time, ecological explanations such as species interactions with the environment, have dominated the field. Only recently has it been acknowledged that community composition must also be determined by historical factors, and as such the future of community ecology and biogeography must bridge ecological and historical paradigms. To this end, BAYESLAND will analyse biogeographical patterns in islands by combining ecological and historical approaches. This will be done by developing new biogeographic models using Bayesian inference for estimating historical processes of community assembly, while also accounting for (i) ecological differences among lineages, and (ii) the influence of ecological factors on historical processes. This project is expected to result in novel cutting-edge analytical techniques in biogeography. In addition, the application of these new tools to extensive molecular datasets from the Canary Islands is likely to offer new predictions on community assembly. BAYESLAND will transfer to the fellow the host's strong experience in analytical biogeography and macro-ecology, complementing his experience in eco-evolutionary studies of island communities. The fellow will develop skills in method development, NGS, theoretical knowledge and project management, which will be paramount to his career development.

Mots clés : biodiversity, community assembly, islands, phylogenetics, bayesian inference

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet PolyDrug Discovery (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Biopharmaceuticals such as monoclonal antibodies (mAbs) and interferons/cytokines have become mainstream since the approval of recombinant human insulin in 1982. However, many challenges such as production costs, output capacity and demanding storage conditions prevent them from realizing their full potential. Therefore, the objective of this action is to develop a polymeric drug (PolyDrug) that mimics the activity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) for the treatment of breast cancer. To do this, multivalent polymers that display peptides (binding epitopes) with high affinity for death receptor 5 (DR5) will be prepared in high-throughput using combinatorial polymer chemistry. Then, the modern drug discovery process will be applied to identify/develop PolyDrugs with the greatest anticancer potential. This includes library preparation in Work Package 1 (WP1), high-throughput screening and hit to lead in WP2, and lead optimization through cell studies and macromolecular modeling in WP 3. Beyond this scope of this action, these efforts will be followed by preclinical and clinical development within a start-up PolyDrug discovery company. With this innovative PolyDrug discovery process, I hypothesize that I will be able to develop polymeric replacements for current biopharmaceuticals including TRAIL.


Participants :
- Karolinska Institutet (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173857.2 €
Projet EMBRACE (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Bladder cancer is the ninth most afflicted cancer in the world which affects people in both developing and developed countries; and European nations have some of the highest incidences. Poor prognosis and mortality rate is very often linked to formation of secondary tumour sites in these patients. In advanced stages of this cancer, cells strive to invade nearby tissues in a process called metastasis. More often than not, patients suffer more due to metastasis of cancer than through the original tumour. In this project, I will investigate the mechanisms which lead to bladder cancer metastasis; identify key components in the pathways and also test out specific inhibitors to mitigate the growth and/or metastasis. Having an acute knowledge of ‘how and which’ pathway(s) promote metastasis in bladder cancer should provide us with information so that specific components can be targeted. Moreover, the proposed study also focuses on developing state-of-the-art biomarker strategies to identify patient populations which will best benefit from our inhibitor therapies. This project will enable the translation of experimental results obtained from lab bench to understanding how some patients will best benefit from certain inhibitor therapies.

Mots clés : ubiquitin, kinase, bladder cancer, transforming growth factor beta, hepatocyte growth factor

Participants :
- Leiden University Medical Center (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 177598.8 €
Projet DECRON (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Blast furnaces are widely used in the iron-making industry. The running of blast furnaces consumes 60% energy of whole steel industry and is primarily responsible for the CO2 blueprints in steel plants. As the steel industry is suffering much with the increase iron ore prices and global economy recession in recent years, it has now become a urgent need to adopt innovative approaches to reduce the production cost in iron-making. It is well recognized that the development of eco-friendly steel plants are urgently demanded. DECRON provides a unique and timely opportunity to bring together the fellow’s research experience in the high performance computing, GPU and discrete element modelling (DEM) with the supervisor’s extensive experience in coupled DEM with computational fluid dynamics (DEM-CFD), particle flow, packing and segregation. This will result in the development of novel charging methods for blast furnaces based upon a thorough micro-mechanistic understanding of the process using GPU-enhanced DEM-CFD, and lead to more precision and better controlled charging systems for blast furnaces. DECRON will for the first time devise an indisputable technological innovation and establish feasible strategies to achieve controlled burden distribution in blast furnaces, which will maximise energy efficiency and reduce CO2 emission in iron-making processes.

Mots clés : particle technology, ironmaking, blast furnace, dem cfd

Participants :
- University of Surrey (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €