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

Alphaviral Immunotherapy against Glioblastoma Glioblastomas (GBM) are the most frequent type of primary brain tumours with no treatment or cure available. Despite the current standard care, GBMs remain 100% fatal with median survival of patients for only 12 - 15 months. Thus, there is an urgent need for novel effective therapies. Among the emerging new therapeutic approaches is oncolytic virotherapy with replicative viruses that kill cancer cells. During his PhD studies, the applicant researcher, Miika Martikainen, has engineered novel tumour-targeted replicative alphavirus that shows promising therapeutic response in a syngeneic orthotropic mouse model for human GBM. As the next step, the applicant seeks to join Professor Magnus Essand’s group at the Uppsala University to conduct his postdoctoral research project that aims to development of clinically relevant oncolytic immunovirotherapy against GBM. To achieve this aim, previously unappreciated potency of Alphaviral oncolytic virotherapy is combined with synergistic immunotherapy with dendritic cell vaccination and/or adenoviruses. A detailed analysis of relevant immune responses associated with the therapy efficacy will be conducted to allow clinical translation of the results. The state-of-the-art methods available and the training received during the fellowship at host laboratory and secondments will arm the applicant with the skills and knowledge that allow him to establish a career as independent research scientist in a field that aims to develop novel ways to treat severe forms cancer.

Mots clés : oncolytic virotherapy, immunotherapy, alphavirus, adenovirus, malignant glioma, dendritic cell vaccination

Participants :
- Uppsala University (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 185857.2 €
Projet QuantMR7 (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Alterations in the intrinsic physical tissue parameters measured with magnetic resonance imaging (MRI), such as of longitudinal (T1) and transverse (T2) relaxation times, have been implicated in major neurological conditions. Although these differences have been noted as useful signs in image contrasts, parameter quantification has not been exploited as a marker for disease stage or for monitoring treatment efficacy. Previous attempts to perform quantitative MRI protocols have suffered from sensitivity to system imperfections as well as infeasible, long acquisition times. Recently, a new approach called MR fingerprinting (MRF) has been developed for the estimation of multiple parameters at once, featuring a new dedicated acquisition strategy. The method has shown great promise as data can be acquired in clinically acceptable time, is relatively insensitive to system imperfections and has high accuracy. To date, only two dimensional datasets using a single acquisition strategy (balanced steady state free precession bSSFP) have been explored. Further, this was using a rather slow reconstruction algorithm at 1.5T. In addition, the technique has not been yet applied outside healthy volunteer groups. In this project we aim to develop a 3D MRF acquisition for imaging the whole brain with optimized acquisition trajectories. We will compare different acquisition strategies, including strategies sensitive to magnetic susceptibility in the brain, previously unexplored. The sequence parameters will be optimized using a dedicated novel genetic algorithm. An accelerated reconstruction software using a novel algorithm will be developed using graphics processing units. Initial data will be acquired with new protocols at 7T and at 1.5T. Statistical parametric maps will be used to investigate group differences. The close interaction with clinical facilities will facilitate the prompt application to patient groups, including neurological, psychiatric and pediatric patients.

Mots clés : neuroimaging, quantitative, brain, mr fingerprinting

Participants :
- Imago 7 fondazione di ricerca onlus (Italie) — Coordinator, beneficiary, Recherche, subvention : 180277.2 €
Projet PREF LEARNHEUR (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Although decision theory assumes that when making a choice, individuals attribute values to available options, compare those values and select the option with the highest, the succession of choices faced during classical preference elicitation tasks might trigger the emergence of additional heuristics, implemented to perform those tasks in a fast, yet adaptive manner. This project aim at pioneering the isolation of such heuristic development, in a dynamical framework where both the task features and the agents’ own preferences are learned from previous trials, and influence subsequent behavior. This framework suggests that agents’ preferences will depend on the choice sequence, thus vary according to predictable patterns through different instantiations of the same task. Thereby, it captures a new component of individual preferences, which we refer to as task-related preferences. Combining behavioral experiments, computational modelling and functional brain imaging, we propose to reveal and measure the behavioral variance accounted by the task-related preferences, to model their emergence during the task, and to incorporate them in a coherent neuro-cognitive model of decision-making. Overall, this project will contribute to 1) refine current neurocognitive and economic models of decision-making, 2) train a promising cognitive neuroscientist to tackle human decision issues relevant to social sciences, with advanced quantitative economic/computational tools, and 3) foster fruitful cross-talks between scholars from economics, psychology, and neuroscience at the host institution. The scientific contribution seems particularly important given that preferences are one of the current conceptual cornerstones used to understand our society at the micro- and macroeconomic level, to guide and assess public policies aiming to maximize people’s well-being, to characterize normal and pathological behaviors, and to unravel the neurobiological mechanisms underlying decision-making.

Mots clés : decision making, fmri, neuroeconomics, computational modelling

Participants :
- University of Amsterdam (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165598.8 €
Projet PERTURBATIONS (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Although genome sequencing is well advanced, our understanding of the genome to phenotype to fitness relationship remains very poor. It is becoming very evident that the information stored in genes is not enough to understand their impact without knowing the phenotypic and environmental context. The fact that a gene is present in a genome tells very little about when it is expressed and its relationship to other genes and mutual effects on gene expression pattern. To understand how phenotypes emerge from a specific genotype, we need to understand gene regulatory networks and their mechanisms of regulation. In this project, I propose to study the relationships between genotype, phenotype, fitness, and environment using a microfluidic device coupled with transcriptomics with the goal of collecting high dimension high quality data for unprecedented level of understanding and predicting regulatory networks, evolution, and evolutionary constraints in the form of epistasis and pleiotropy. I will use programmable DNA binding protein called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to perturb gene expression of (1) combinatorial global regulators within the transcriptional regulatory network, (2) cascades of genes that form gene network hierarchy, and (3) single global regulators with low level mutations at many positions in their genetic code. I will then quantify the expression pattern of the transcriptome using RNA sequencing and the growth fitness of each strain. The environment will be highly controllable as we will create a cutting-edge microfluidic system to study many strains of bacteria in a high-throughput manner. Successful implementation of the strategies explored in this project will open the doors to plenty of other avenues to explore with fruitful outcomes wherever there is a need for combining genotypic, phenotypic, and fitness studies in highly controllable environments

Mots clés : systems biology, evolutionary adaptations, transcriptional network, genotype to phenotype mapping, crispr editing, microfluidics, rna sequencing, biophysics

Participants :
- École supérieure de physique et de chimie industrielles de la ville de Paris (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 184707.84 €
Projet VirIVITES (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Although inflammatory and neurological diseases caused by arthropod-borne viruses progress worldwide, biomedical advances are slow, still leaving patients to palliative care. New approaches to arboviral pathogenesis are needed to overcome the limitations imposed by inappropriate experimental systems. Here I propose to use tissue-engineered human skin, comprising immune cells and sensory nerve cells, and naturally-infected mosquitos to investigate infection and cell responses to the Dengue arbovirus. I will benefit from the host organization experience to perform (i) primary and induced pluripotent stem cell cultures and differentiation of dendritic cells, macrophages and sensory neurons, followed by their three-dimensional assembly, (ii) Dengue virus infection of mosquitos and (iii) analysis of cell infection and cell responses using virology, molecular biology and microscopy tools. In return, I will apply my skills in single cell transcriptomics of skin to explore the feasibility to apply this new technology to reconstructed tissue. Thanks to excellent scientific and soft skill training as well as the favourable arrangements provided by the host organization, the deliverables of this interdisciplinary research programme should be attainable in 24 months. In addition, I aim to gain professional maturity by proposing new projects for financing as a result of ideas, knowledge and collaborative links. The demonstration that human sensory neurons are infected by the Dengue virus in reconstructed skin should make an important impact for new biomedical approaches to prevent/treat neurological diseases caused by arboviruses. My objective is also is to have contributed to the progress of the host organization while evolving professionally for a stable employment in Europe.

Mots clés : skin, mosquito, arbovirus

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

Aluminium (Al) alloys are extensively used in transport (28%), construction (35%) and engineering (27%) sectors. The total Al in use is expected to increase from 600 million tonnes in 2013 to one billion tonnes by 2020, thus creating a large metal bank for future recycling use. Currently primary Al production from bauxite ore is the primary source of Al metal supply to industry. Since primary aluminium production is an energy intensive process and the world's bauxite deposits are limited, the use of Al scrap accumulated from packaging, building, automotive and engineering sectors offers a sustainable solution to secure metal supply. However, the scrap from these sectors has higher levels impurities in particular with iron (Fe). Higher concentration of Fe is detrimental to the mechanical properties due to formation of harmful platelet structures of Fe-based intermetallics. The overall aim for the fellowship is to develop solidification science based methods which enables the use of aluminium scrap alloys to produce high value aluminium products to support the rapid growth of Al. The objectives are (i) To develop methods to tolerate higher iron impurity concentrations in Al scrap alloys using model alloys containing impurities, through enhanced heterogeneous nucleation, intermetallic morphology control and restricting their growth (ii) to understand the solidification behaviour of scrap alloys by attempting to tackle the problem from thermodynamic analysis, engineering the microstructure through various approaches and an in-depth understanding of the behaviour of intermetallics using advanced tools, examine the effect of impurities on properties and to determine micro-mechanical properties of various synthetic iron based intermetallic phases, (iii) to build an open access database for impurity levels in scrap alloys-property-process dependence and to provide guidelines for Al component manufacturers on critical levels of impurities in specific alloys.

Mots clés : recycling of aluminium scrap alloys, light metals, nucleation and growth

Participants :
- Brunel University London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet THAUMECOPHYL (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Ammonia oxidizing archaea (AOA), a clade of the Thaumarchaeota phylum, diversified in a variety of marine and terrestrial environments. Due to their abundance, AOA are deemed major players in the global cycle of nitrogen. They also produce greenhouse gasses. Despite their ecological importance, the nature and origin of ammonia oxidizing metabolism and the reasons for the ecological success of AOA are still unknown. This project aims at performing the first comprehensive evolutionary and comparative genomic analysis of Thaumarchaeota to identify crucial metabolic and genomic features. Prof. Schleper is a leading scientist in Thaumarchaeota cultivation, genomics and physiology. Metagenomic data produced in her laboratory give now access to genomes of crucial taxa for this project. I will complete these genomes, and analyse all available AOA genomes with a sophisticated model of genome evolution to reconstruct the species tree of Thaumarchaeota and the events (gene duplications, transfers and losses) that occurred along their evolution. The genome of the AOA’s ancestor will be inferred, and the minimal gene set required for ammonia oxidation identified. The sets of evolutionary events and the ancestral genome will be linked to metabolic and ecological transitions to obtain the scenario of ammonia oxidation emergence and of the adaptation of AOA to various environments, thus addressing key questions in the fields of ecology, evolution, and archaea biology. This interdisciplinary project is only possible through the unique combination of my expertise in comparative genomics and molecular phylogeny with the expertise of Prof. Schleper's group, which will result in two-ways transfers of knowledge and skills. Beyond scientific training, I will be trained to project management and project design with experimental biologists. This is crucial for my career, as I plan to start a group at the edge of bioinformatics and experimental biology to study how complex systems evolve.

Mots clés : archaea, genome evolution, ecological adaptation, phylogenomics, metagenomics, genome assembly, ammonia oxidation, nitrification, nitrogen cycle

Participants :
- University of Vienna (Autriche) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178156.8 €
Projet T-REX (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Among the greatest challenges of the 21st century are bacterial diseases that permanently threat plants and animals, including humans to whom they often are lethal. In plant and animal production, bacteria can cause severe yield reductions if not effectively controlled. However, the current control measures include use of environmentally problematic antibiotics, which in addition may lead to appearance of bacterial strains resistant to these antibiotics. Recent progress in the host laboratory using a Genome Wide Association Study (GWAS) of wheat reveals a hitherto unknown recognition mechanism of the effector translocator widely conserved in pathogenic bacteria. The associated receptor complex is predicted to have wide potential for exploitation in bacterial disease control, not only in crop plants but also in livestock production. In the T-REX project, number of parallel efforts will be taken to characterize the recognized T3SS component, the membrane bound receptor complex and the activated immunity. This will be undertaken using an integrated approach, which involves my background knowledge and experiences combined with the ones of the host institution within molecular genetics, biochemistry, molecular biology and bioinformatics. This study will shed light on the role of T3SS as a PAMP, which will help us to elucidate the complex plant-bacterial interactions and can potentially lead to the development of new phyto-pathogen control strategies. T3SS being conserved among plant and animal pathogen, the outcome of the T-REX project has potential for extrapolation into animal pathological systems, including humans, and may contribute to the world of medicine.

Mots clés : bacteria, t3ss, plant defense, wheat

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet ADELE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disorder caused by the loss of motoneurons in the brain and spinal cord. Each year, ALS is responsible for three-five deaths per 100000 people. ALS initiates in mid-life by muscle weakness, evolving rapidly into a generalized paralysis that leads irrevocably to death within 2-3 years of clinical onset. Despite an exploding knowledge of pathological processes acquired in adult subjects, successive clinical failures suggest that our way to consider and treat the pathology may not be the most pertinent and effective. The idea that the pathology can originate during development has received very little attention, while in the post-natal period the fundamentals of the sensorimotor system are being laid, its completeness will be central for the rest of our days. ADELE project proposes to explore ALS as a developmental disease that take roots during critical developmental stages when the synchronized activity of sensorimotor circuits is established, and that subclinical threshold defects remains silent before reaching a clinical break point. This conceptual progress, with diagnostic and early therapeutic implications, can be made possible with the recent access to network activity of the spinal cord in rodent neonates. ADELE proposes to 1) investigate the spatiotemporal network dynamics in ALS mouse neonates by recording field activity using multi-electrode array along the spinal laminae, 2) to complete this approach by behavioral study of proprioceptive integration, which is detrimental for spinal circuitry function and 3) identify activity modulating drug to restore early spinal network dynamics and subsequently influence the course of the disease. Our multidisciplinary strategy will fill knowledge gaps with the goal to propose new therapeutic intervention and open up new horizons for the patients.

Mots clés : amyotrophic lateral sclerosis, sensorimotor development, spinal circuitry, local field potential, multi unit array, behaviour, therapy

Participants :
- Kazan Federal University (Russie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Institut national de la santé et de la recherche médicale (France) — Coordinator, beneficiary, Recherche, subvention : 190676.16 €
Projet Chenitar (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

An ambitious and multidisciplinary project is proposed to identify on the large scale the molecular targets of different chemical forms of nickel in some human cells. For this aim, a comprehensive and multidisciplinary program is proposed, including toxicity assays, non-denaturing procedures and the development of analytical schemes based on multidimensional electrophoresis and chromatographic separation. Despite nickel is classified as carcinogenic and nickel allergy is common worldwide, the molecular mechanisms responsible of nickel toxicity are not know. In this sense, to determine the carcinogenicity potential of nickel compounds, the information about the molecular targets of nickel is critical. There is an urgent need to obtain information about the molecular target depending on the chemical form of nickel, as they are not known yet. This project will study a broad range of different chemical forms of nickel in two selected human cells. Cells will be incubated with the different chemical forms in different conditions and the cytotoxicity will be measured. In order to isolate the native nickel complexes, an optimal non-denaturing procedure of will be developed. Information about the uptake of nickel to cells will be obtained and correlated with the citotoxicity results. Lastly, the identification of the molecular targets will be carried out through the development of novel analytical strategies based on the combination of different separation techniques with different detection techniques. The great novelty of this project is based on the combination of the information obatined about nickel toxicity and nickel uptake with molecular nickel speciation. The information obtained in the project will help to future understanding of molecular mechanisms of nickel related to nickel allergy and nickel carcenogicity. Additionally, the understanding of these molecular mechanisms will also help to the understanding on the mechanisms of other metal allergies.

Mots clés : nickel allergy, nickel carcinogenicity, analytical method development, molecular targets, electrophoresis, chromatography, mass spectrometry

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