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

Projects in the nuclear sector – such as the construction of nuclear power stations, management of high-level radioactive waste, or decommissioning of old installations – can be seen as a specific category of megaprojects. These large-scale, complex infrastructure projects are typically commissioned by governments, often delivered through public-private partnerships, and involve multiple partners, high uncertainties, and considerable political stakes. Such projects are prone to generate significant controversies, as they often run over budget, exhibit delays in planning and construction, and fail to deliver the initially foreseen benefits to the society. The controversies, so-called megaproject pathologies, and the possible means of alleviating the problems coevolve with the country-specific context – the "technopolitical regimes” or "technopolitical cultures". This project will explore such pathologies, controversies and various types of appraisal in nuclear sector megaprojects in Finland, France, Spain, and the UK. Combining various strands of literature (megaproject governance and evaluation, programme and policy evaluation, ex ante assessment, pragmatic sociology, and Science and Technology Studies), and drawing on my recent and on-going research on governance and history of nuclear power, citizen engagement, the role of expertise, and megaproject evaluation, I address the following overall research question: In the light of historical and contemporary examples of controversies over nuclear economics, in the context of the socioeconomic appraisal practices in Finland, France, Spain and the UK, under which preconditions could economic controversies play a constructive role and help address megaproject pathologies in socioeconomic appraisal, within diverse technopolitical regimes and cultures? Research methods include document analysis, interviews, and semi-qualitative sociolinguistic analysis of text corpuses, especially with the help of the “Prospéro” software.

Mots clés : megaprojects, nuclear power, radioactive waste management policy, role of expertise, public participation, policy appraisal, policy evaluation, public controversies, economic sociology and history

Participants :
- Pompeu Fabra University (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 158121.6 €
Projet NewPropChem (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Propellanes are molecules of high importance as precursors to valuable cage molecules in pharmaceutical and materials research. For smaller-ring propellanes, ubiquitous reactivity can be displayed towards anions, radicals, and cations; however, the theoretical basis for this unusual behaviour has only recently emerged, which is based on the ability of small ring propellanes to delocalise electron density away from the electron-rich central C–C bond onto the peripheral carbon atom p orbitals both in the ground state, and during reactions. In this project we develop chemical tools to test this theoretical model, offering experimental support and characterising the change in structure and electronics during ring opening processes. We further develop new synthetic methodology to access high-value (but hard to access) chiral propellane ring-opening products, and explore new modes of propellane reactivity by employing novel catalytic concepts to activate the central C–C bond. We use a theoretical 'carbene' description of [1.1.1]propellane to open up access to bridge-substituted propellanes, which represent a 'holy grail' of the field, and also explore methods to control the dimerisation or oligomerisation of these molecules. Collectively, using the most up to date theoretical models (and in collaboration with theoretical chemists) we aim to develop a new frontier of propellane chemistry, which has the potential for broad impact on its many applications.

Mots clés : propellanes, catalysis, mechanistic studies, theoretical calculations

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet TSILENCICH (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Proper regulation of transposable elements (TEs) by Piwi-interacting RNAs (piRNAs) is critical for fertility and embryogenesis in animals. Because TEs need to evade silencing to replicate, they are engaged in an evolutionary arms race-type of genetic conflict with their host. These arms races between TEs and the piRNA pathway result in rapid evolution of piRNAs and piRNA regulatory factors, which in turn leads to genetic incompatibilities observable in interspecific hybrids that are relevant to speciation. New evidence supports the fast evolution of piRNA pathway factors in the cichlid radiation of Lake Malawi, where 800-1000 different species have evolved in only 800,000 years. The main objective of TSILENCICH is to understand how TEs and piRNAs co-evolved in these animals, throughout their explosive diversification. I have recently identified an expansion of piRNA pathway factors in Lake Malawi cichlids. While these factors are enriched in the germline in most metazoan species, in cichlids these genes exhibit remarkably higher expression in the brain, suggesting novel functions. I will construct new tools to test if piRNAs regulate the expression of TEs in the cichlid brain, and what role this regulation might play in brain development. In addition, I will test the hypothesis that TE epigenetic silencing is compromised in cichlid interspecific hybrids, utilizing A. calliptera and Tropheops sp. mauve, two cichlids with distinct eco-morphological and behavioural characteristics, and their hybrids. I will profile the epigenetic landscape in the parental species, as well as in fertile F1 and F2 hybrids, to investigate if TE expression becomes progressively more imbalanced across generations. The proposed work will shed light on the origin of piRNA pathway/TE conflicts and on novel somatic piRNA-driven TE epigenetic silencing in vertebrates.

Mots clés : epigenetics, pirnas, transposable elements, piwi argonaute, dna methylation, genetic conflict

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet EcoEvoProspectS (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Prospecting behaviours allow individuals to gather personal and social information on the local quality of potential future breeding sites and help them make dispersal and settlement decisions. As it can have multiple consequences on individual distribution, fitness and population dynamics, exploring the ecology and evolution of prospecting strategies is essential in a context of climate change. Yet, studies dealing with this topic are scarce because of methodological and technological challenges. In this project, I will develop and apply novel theoretical and statistical approaches to deliver major new insights into the adaptive, ecological and evolutionary importance of prospecting strategies in individual and population responses to environmental change. First, I will develop a spatially-explicit individual-based model to quantify the effects of local environmental conditions, life history traits and range margins on the evolution of prospecting strategies. I will also test how inter-individual variation in these strategies may help or hinder populations in responding to rapid environmental change. Second, I will extend a state-space model to robustly quantify prospecting movements from GPS tracking data. This will provide an innovative and powerful tool that will give new insights into the behavioural mechanisms involved in breeding habitat selection. Finally, I will integrate the underpinning knowledge gained from the theoretical and empirical results to add new functionality to the existing platform RangeShifter. The multidisciplinary nature of the project is strong, involving a combination of evolutionary biology, behavioural ecology, movement ecology and conservation biology. The project will open new perspectives in our fundamental understanding of breeding habitat selection and dispersal processes and will be essential to better predict and effectively manage species’ responses to climate change.

Mots clés : social information use, informed dispersal, breeding habitat selection

Participants :
- University of Aberdeen (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet POLAR STAR (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Prostate cancer (PC) is the fifth leading cause of cancer-related death worldwide. PC often presents in its Multidrug resistant form leaving the patient few survival chances. New approaches are required to overcome resistance-related problems in PC and nanomedicine holds a lot of premises to effectively contribute in this battle. In this frame POLAR STAR aims at the implementation of combination therapy to treat castrate-resistant PC. Our strategy is to exploit innovative nanotechnology to administer contemporarily different therapeutic agents that synergically exert their activity across multiple oncogenic pathways. We plan to use new mixed polymers based on biocompatible cyclodextrins as these building blocks are already FDA approved. Simple organic chemistry is pursued to implement target selectivity and in vivo tracking of the polymeric nanocarrier. The design is guided by the final goal, the future clinical application of nanocarriers to improve PC treatment, keeping in mind upgrade of the nanocarrier systems to large scale production. We will focus on the latest PC drugs suffering from side effects and emerging resistance as multiple cargo to be loaded. Full chemico-physical characterization of the systems is planned as well as assessment of the efficacy of loaded nanocarriers in cell cultures with different drug responsivity profiles. In order to reduce animal experiments POLAR STAR will take full advantage of 3D prostate tissue models for biological tests, an apporach at the forefront in drug design. We plan to reach our goal bringing together the expertise of the fellow and the supervisor supported by the private and academic teams hosting the fellow during secondments. POLAR STAR creates a multidisciplinary environment where all actors, public and private, will benefit from reciprocal transfer of knowledge. During the project the fellow will have the possibility to become a complete researcher improving also complementary skills.

Mots clés : 3d prostate cancer model, multi drug resistance

Participants :
- National Research Council (Italie) — Coordinator, beneficiary, Recherche, subvention : 171473.28 €
Projet SCEPTRE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Prostate cancer (PrCa) is the most frequently diagnosed cancer in men in the European Union (EU), and is a molecularly and clinically heterogeneous disease. Although the genomic and transcriptomic landscapes of PrCa have been characterized deeply, the genome-wide epigenetic landscape and its contribution to tumor heterogeneity has received less attention. The lack of single-cell methylation (with parallel single-cell transcriptomic) datasets in solid tumors (and none in PrCA) has stunted inference on clonal evolution. Consequently, the understanding of the coordinated relationship between methylation and transcriptome remains tenuous at best. Structural variants have also not been able to be accurately resolved in cancer due to the reliance on short-read sequencing, and their interplay with DNA methylation is still poorly understood. I present the project, SCEPTRE which is tightly connected to and builds upon ample expertise in the laboratories of Prof. Christoph Plass, Division Chair of Cancer Epigenomics, DKFZ, and Dr. Oliver Stegle, Division Chair of Computational Genomics, DKFZ. Within this project, I will drive the generation of novel ‘single-cell’ and ‘single-molecule long-read’ PrCa datasets, and exploit existing data resources to comprehensively assess the epigenetic and joint transcriptomic and genomic dimensions of human PrCa with the aim to examine cancer evolution. To realize this aim, I will also derive a comprehensive computational toolbox for the analysis of single-cell (and single-molecule) DNA methylation and joint multi-omic profiles. This project will deliver novel innovative ways to identify epigenetic drivers; as well as link DNA methylation for lineage tracing as a biomarker for disease progression. Moreover, the project will uncover putative relationships between the DNA methylome and transcriptome as well as between structural genetic aberrations and epigenetic changes.

Mots clés : bioinformatics, single cell, nanopore, multi omics

Participants :
- German Cancer Research Center (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 174806.4 €
Projet AR-DDR (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Prostate cancer is the 2nd most common cancer in the western world. The advanced stage, metastatic castration-resistant prostate cancer (mCRPC), is a lethal disease. Understanding inter-patient genomic heterogeneity renders the opportunity to advance towards personalised patient care. Prostate cancer is a disease primarily driven by the androgen receptor (AR) pathway; however, the applicant prior work contributed to identifying 1) that up to 25% of mCRPC harbour defects in DNA damage repair (DDR) genes, and 2) that some of these mCPRC patients with DDR defects are sensitive to targeted treatment with PARP inhibitors. In the proposed research plan, we aim to exploit the cross-regulation between AR and DDR pathways to optimize precise therapeutic options for mCRPC patients. To achieve the objectives, the applicant will use models generated at the host through CRISRP/Cas9 to pursue functional studies and characterise how defects in ATM impact DDR function and sensitivity to inhibitors of PARP, ATR and DNA-PK. We hypothesize such sensitivity would be modulated by co-targeting of the AR pathway and by second events such as TP53 loss-of-function. ChIP-Seq assays will be pursued to identify genes co-regulated by the androgen receptor and PARP-1, to identify potential synthetic vulnerabilities. Then, mCRPC patient’s biopsies acquired in clinical practice from patients receiving AR-targeting therapies will be used to study how AR inhibition modulate transcriptional regulation of DDR pathways, to inform the optimal design of combination therapies. These data would be correlated with genomics and immunofluorescence tests of homologous recombination function, in order to refine patient stratification in the clinic. The proposed research will be conducted in parallel to a personalised training and career development plans, designed for the applicant to achieve a position of academic independence as physician-scientist before the end of the fellowship at the host institute.

Mots clés : prostate cancer, dna repair, biomarkers, tp53, parp

Participants :
- CERCA Institution (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet NeuroRhomboid (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Proteases control major pathways in the nervous system and aberrant proteolysis underlies many neurobiological disorders and diseases e.g. Alzheimer's and Parkinson's disease. Signal generation and release is tightly regulated by protease activity, as many key signalling factors are synthesised as transmembrane precursors that require cleavage to liberate their active ectodomains. The largest family of intramembrane proteases are the newly discovered rhomboids, which are found in all kingdoms of life. To date, their physiological significance in mammals is largely unknown, as is the substrate-selectivity of most mammalian rhomboids. I have exciting preliminary data that two uncharacterised mammalian rhomboids, RHBDL1 and RHBDL3, are specifically highly expressed in primary neurons in the CNS. Unlike the well-studied RHBDL2 and Drosophila rhomboids 1-3, they do not have activity against EGF-like growth factors, so they are likely to cleave a novel substrate. A major limitation in protease research has been the lack of unbiased and systematic screens for their substrates. Addressing this deficiency, first, I aim to identify RHBDL1/3-dependent substrates in primary neurons, by adapting recently developed biochemical assays, such as SPECS and BioID. My second aim is the mechanistic validation of these substrates. Third, I will be the first to study the physiological role for active rhomboids, using CRISPR-mediated knock-out neurons and mice. By discovering the role and function of RHBDL1/3 in the brain, I will make an important contribution towards the elucidation of the physiological and medical significance of rhomboid proteases in mammals.

Mots clés : protease, signalling, rhomboid, neuron, bioid, specs, crispr, knock out mice

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet LCxLCProt (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protein biopharmaceuticals, which globally represent about 20 % of the total pharmaceutical market, are becoming increasingly popular in the treatment of various diseases. Experts forecast that over 50 % of new drug approvals in the next decade will be for biologics, especially monoclonal antibodies. Very accurate structural characterization and purity analysis is required during both the development of the new drugs, and later during manufacturing for quality control purposes. Biopharmaceutical protein molecules are very large and heterogeneous, which makes their characterization very difficult. The goal of this project is to develop novel methods for the characterization of protein biopharmaceuticals at the protein level based on comprehensive two-dimensional liquid chromatography (LC×LC). Two approaches will be explored: the use of reversed phase separation mechanism in both dimensions with parallel gradients, and application of thermally responsive stationary phases for thermal modulation of LC×LC fractions. Parallel gradients provide the greatest orthogonality when the separation mechanisms in both dimensions are correlated, and allow the use of short modulation periods, which together lead to a dramatic increase in peak capacity (as demonstrated in preliminary experiments). Thermally responsive stationary phases allow trapping of the analyte bands at elevated temperatures, and their release at low temperature. This is compatible with intact protein analysis, especially when ion exchange is used in the first dimension of the LC×LC system. It is expected that the research will result in new, cutting edge methods for the analysis and characterization of protein biopharmaceuticals that will be applicable under the good manufacturing practice (GMP) conditions, improving the quality assurance/quality control and increasing the confidence in the pharmaceuticals.

Mots clés : comprehensive two dimensional liquid chromatography, protein biopharmaceuticals, intact proteins, thermal modulation

Participants :
- Ghent University (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 89160.0 €
Projet Protprot (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protein post-translational modification is an essential feature of living systems; one of the most common post-translational modifications is phosphorylation. Phosphorylation of proteins is central both to direct regulation of activity and to protein-protein interactions. Within this project we will use the study of a model regulatory protein-protein interaction, dependent upon phosphorylation to provide a training platform in biophysical and structural approaches to protein-protein interactions. The particular protein-protein interaction is the phosphohistidine/phosphothreonine-dependent interaction of the plant and bacterial enzyme, PPDK, with its regulatory protein PDRP. This regulatory protein appears to be central to the efficiency of photosynthesis in those plants using the C4 pathway of CO2 fixation as well as to the regulation of bacterial growth yet little is known about the molecular details of its action. Protein-protein interactions such as the PPDK-PDRP are ubiquitous in biological systems, it is the combination of thousands of such pair-wise interactions that lead to the collective properties of all cells. The ability to characterise each individual interaction thoroughly in vitro is essential for the continued development of both our understanding of the cell and how to manipulate this behaviour in therapeutics. Through this fellowship, the experienced researcher, Dr Witkowska, will gain essential hands-on experience with the application of the full range of contemporary approaches to such interactions which will enable her to establish herself as an independent researcher in the area upon her return to her home country while maintaining research links with the host laboratory.

Mots clés : protein protein interactions, protein phosphorylation, amino acid analogues

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