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

Rare diseases are a major unmet medical need, as is the definition of the relevant disease mechanisms. Many rare diseases affect the nervous system. These are challenging to treat, and mechanistic studies are difficult due to the inaccessibility of patient tissue. Global proteomic studies have provided insight into whole tissue or cell changes in protein abundance but lose information on protein subcellular localisation, which is important because defects in protein trafficking are implicated in many neurological disorders. In ‘RARE MAPS’ I propose an unbiased mechanistic discovery pipeline combining human induced pluripotent stem cells (hiPSCs) with advanced spatial proteomics. I will use a method developed by Dr. Borner called ‘dynamic organellar maps’, which provides quantitative protein subcellular localisation information at the whole proteome level. Used comparatively, it can detect changes in protein localisation due to a perturbation, allowing unbiased screening for phenotypic changes. To develop this workflow, I will apply it to the rare neurodegenerative disorder AP-4 deficiency syndrome. AP-4 knockout hiPSCs will be differentiated into cortical neurons and maps will be made of intermediate cortical stem cells and mature cortical neurons. Comparison to control cells will enable the detection of changes to protein localisation and abundance. I will also apply the maps to brain tissue from an AP-4 deficient mouse model to detect protein mislocalisation in vivo. I will then use CRISPR/Cas9 technology to investigate the role of novel and known AP-4-associated proteins in neuronal autophagy and axonal health. This project will demonstrate the utility of dynamic organellar maps to reveal molecular mechanisms of rare neurological disorders as well as provide new insights into the pathogenesis of AP-4 deficiency and the role of protein trafficking and autophagy in the axon.

Mots clés : mass spectrometry, induced pluripotent stem cell, neuron, axon, gene editing, crispr, adaptor protein complex, autophagy, neurodegeneration, hereditary spastic paraplegia, vesicles

Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 162806.4 €
Projet ReMedIt (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

ReMedIt aims to provide the first historical reconstruction of the evolution of views on the medieval Italian vernacular literary tradition in Italy during the period that leads to the formation of an established canon of vernacular literary authors (1476-1530). The project focuses on the reception of the poetic tradition, in particular the extensive Italian lyric tradition (c. 1230-c. 1330) preceding Petrarch, one encompassing over two hundred authors. The project interrogates three main interrelated research strands: 1) the differing value judgements concerning the vernacular poetic past before Petrarch, both implicit ones (such as the selection of poets, their ordering, and the amount of attention afforded them in different poetic anthologies) and explicit comments and judgements; 2) the complex processes – material, interpretative, exegetical and cultural – that bring about the recovery of the medieval lyric tradition and generate knowledge related to it; and 3) the literary influence that this tradition exercised upon verse production during the same period 1476-1530 in the output of nine authors. In order to reconstruct the differing views regarding the genesis and historical development of the earlier Italian literary tradition, the project offers a novel interdisciplinary approach. It does this by integrating the study of how Renaissance poets were influenced by thirteenth- and fourteenth-century authors with an assessment of their critical reception and of the contemporary processes of recovery of their texts. In doing so, ReMedIt will offer a fuller and enriched understanding of this seminal period in the development of the history and codification of the vernacular literary tradition, thereby providing a case study that will be valuable for the study of other national literatures. Through a carefully constructed training-through-research programme the experienced researcher will expand her research interests broadening her chronological range.


Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet FraMoS (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Recent advances in Computational Mechanics are towards the development of predictive tools that can accelerate the 'Materials Development Cycle' by unraveling the linkage between macroscopic properties and microstructure. The availability of 3D tomographic tools and the era of Exascale computing have initiated the quest to develop stronger, tougher and more durable alloys by employing 'virtual predictions' in lieu of expensive destructive testing. However, our lack of understanding of the 'structure-toughness’ relations is one of the main bottlenecks in this pursuit. Moreover, the uptake of some of these new alloys (TRIP, TWIP etc) is hampered by the concerns of hydrogen (H) induced cracking. Existing models have limitations in describing the role of microstructural heterogeneities on mechanisms of fracture in HSS. The proposed research will develop high fidelity continuum models to cover the entire spectrum of mechanisms from fully ductile fracture to quasi-cleavage failure of HSS in H-environment. Among the various mechanisms of H-assisted cracking, hydrogen embrittlement (HE) is one of the most devastating, yet least understood, mechanism of failure in HSS. In this work, realistic models of void nucleation accounting for the dislocations interactions with the second phase particles will be developed. The proposed models of void growth and coalescence will incorporate the microstructural length scales, thus, eliminating the deficiencies of the existing 'damage models'. The micromechanical models of HE developed in this work will incorporate the influence of hydrogen on the initiation and propagation of microcracks leading to complete failure. These models will be integrated with the most advanced models of H-diffusion and trapping (being developed at Oxford) to describe the detailed mechanism of fracture at crack tip in HSS. It is expected that this work will bring, in due course, significant international recognition for its fundamental and applied contribution

Mots clés : ductile fracture, materials modelling, microstructure, non local continuum mechanics, hydrogen embrittlement

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

Recent data coming from both basic research and clinical trials converge toward the importance of the epithelial/mesenchymal status of a tumor to respond to conventional chemotherapies and immune-checkpoint inhibitors. These observations set the Epithelial-to-Mesenchymal Transition (EMT) program at the centre of cancer biology. Besides its multiple roles in development and during adulthood, EMT is activated during tumor progression not only to allow metastatic dissemination of cancer cells, which is responsible for the vast majority of patients’ death, but also to provide cells with stem-like properties and resistance mechanisms to survive chemotherapy. It is now widely accepted that future therapies will have to target and/or block the EMT process and allow conventional therapies to efficiently kill the differentiated, epithelial cells to treat patients with advanced solid tumors. NetriCan will analyse for the first time the implication of netrin-1 and its dependence receptor UNC5B in the regulation of EMT, either directly or via its cell death-related function. Moreover, the re-epithelialization effect of the anti-netrin-1 monoclonal antibody observed in tumors in vivo and in a preliminary cohort of patients shows that netrin-1/UNC5B may not only be involved in the direct regulation of maintenance of EMT but also serve as a survival mechanism for metastatic tumor cells. To achieve this, Netrican will first analyse how the upregulation of netrin-1 and UNC5B is regulated during EMT. It will then investigate the role of the netrin-1/UNC5B axis in the establishment and maintenance of the EMT program needed for cell dissemination and metastasis. Finally, this project will elucidate the therapeutic potential of the anti-netrin-1 strategy for both triggering primary tumor re-epithelialization and killing mesenchymal tumor cells. In summary, NetriCan will provide innovative findings to develop novel promising therapeutic approach for patients with advanced solid tumors.

Mots clés : netrin 1, unc5b, dependence receptors, epithelial to mesenchymal transition, cancer

Participants :
- Université Claude Bernard - Lyon 1 (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 196707.84 €
Projet ERA (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Recent innovations in family policy extend parental leave benefits to fathers and establish paid family leave to care for non-child relatives, such as spouses and parents. Such policies seek to ease work-life tensions, yet there are considerable cross-country differences in the existence, duration and generosity of paid parental and family leave benefits. While welfare state theories offer several explanations for cross-country differences in family policies, we have few explanations for policy content – who is included and excluded from provisions – and the timing of policy change. ERA will apply a unique, recursive mixed-method approach to understand the nature and extent of interactions between various key actors, such as representatives from government, organized labor, women’s movements and organizations opposed to reform, and how such interactions shape family policies. While my quantitative approach will consider the timing of parental leave policy adoption, my qualitative approach will focus on how specific family members – particularly non-child relatives – become incorporated under leave law. Analysis will combine insights from interdisciplinary fields of social movement outcomes (in sociology) and comparative policy analysis (in sociology and political science) and make theoretical contributions to both fields. ERA is a cross-sectoral, interdisciplinary and gender-mindful project that includes end-users in project implementation and an ambitious dissemination, communication and outreach strategy. I bring close to 10 years of experience working in interdisciplinary research centers, publishing independently and with collaborators and expertise in social movements and mixed methods. Collaboration with researchers at the interdisciplinary Swedish Institute for Social Research promises new competencies in policy research and comparative policy analysis and will result in a new, publicly accessible data module, facilitating future cutting-edge research.

Mots clés : comparative policy analysis, social movement outcomes, parental leave, family leave, labour unions, women s movements

Participants :
- Stockholm University (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 185857.2 €
Projet NanoArray (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Recently developed experimental techniques for cooling, trapping and localizing atoms near nanostructures, such as one-dimensional nanoscopic waveguides, offer a new paradigm to investigate quantum light-matter interactions. Collective coherent effects in such engineered interfaces pave the way to integrated quantum technology applications, including single-photon sources and efficient quantum memory for light. The present project investigates this approach based on arrays of cold atoms trapped in the vicinity of a nanofiber. In parallel to experimental developments at the host, this project will develop the theoretical framework of photon scattering in commensurate and non-commensurate arrays and will include ab-initio microscopic description of the interaction. Bragg scattering and superradiance effect will be studied to obtain larger efficiency than previous ensemble-based implementations. Waveguide-mediated long-range organization of the array will also be investigated.

Mots clés : nanophotonics, waveguide, optical lattice, collective effect, quantum transport

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

Recently discovered subtypes in pancreatic ductal adenocarcinoma (PDAC) have potential to better guide the choice of therapy. However, this is challenged by the lack of robust data, patient heterogeneity, tumour cell plasticity, dynamic crosstalk with surrounding cells, and post-chemotherapy induced alterations. A few transcription factors may act as drivers of specific PDAC subtypes and changes in there expression through aberrant activation of super-enhancers may lead to ‘’subtype switching’’. However, the effect of the tumour-microenvironment on enhancer-driven gene expression programme to promote ‘’subtype switching’’ in pancreatic tumour cells remains largely unexplored. Hence, with this proposal I aim to provide in-depth characterization of this dynamic crosstalk combining reporter tracing through fluorescent labelling of subtype-specific transcriptional drivers of tumour cell states with powerful high throughput single-cell technologies, and super-enhancer single cell profiling which will translate to a clinical study of neoadjuvant chemotherapy with sequential tumour sample profiling. This work will ultimately provide a platform for the development of methods to precisely determine the "phenotypic" state of PDAC cells and aid in designing new agents to target these processes, with the ultimate goal of converting non-responder to responder tumours and improve patient outcome.

Mots clés : pdac, plasticity, tumour microenvironment, super enhancers, therapy

Participants :
- Spanish National Cancer Research Centre (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet VCSD (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Recently, it has become evident that the spatial organization of chromatin within nuclei is a key factor that can regulate gene silencing and expression. This organization is particularly important in pluripotent stem cells that differentiate into all cell types of the body through chromatin remodelling coupled to altered gene expression. Therapeutic use of these cells demands precise control over chromatin structure to direct differentiation. However, chromatin structure remains poorly resolved due to the nanometre length scales involved and limitations of low spatial resolution, poor signal-to-noise and ensemble averaging in existing methods. VCSD utilizes cutting-edge super-resolution fluorescence microscopy (SRFM) that overcomes these limitations. VCSD will, for the first time: 1) visualize global, 3D chromatin nanoscale structure in individual cells during differentiation; and 2) correlate the dynamics of local chromatin restructuring with the silencing of a central pluripotency gene. The proposed Marie Curie Fellow, Jason Otterstrom, PhD Harvard Biophysics, has extensive experience in fluorescence microscopy applied to biological systems. The host lab supervisor, Dr. Loza-Alvarez, is an expert in SRFM, at the Institute for Photonic Sciences, Barcelona. A secondment is planned in the lab of Dr. Cosma, an expert in the genetic mechanisms controlling pluripotency, at the Barcelona Center for Genomic Regulation. The combined expertise of the fellow and host labs is uniquely suited to establish VCSD as a novel framework for characterizing chromatin structure. The methodology developed is anticipated to be adopted by researchers in stem cell and chromatin biology fields, thereby reinforcing Europe’s global reputation in scientific innovation. The Fellowship will enable Jason to pursue applications of the chromatin structural metrics determined here as an independent biophysical researcher, with the long-term goal of commercializing a stem cell classification system.

Mots clés : chromatin structure, super resolution fluorescence microscopy, pluripotent stem cells, cellular differentiation, correlative fluorescence imaging, 3d fluorescence imaging

Participants :
- Institute of Photonic Sciences (Espagne) — Coordinator, beneficiary, Recherche, subvention : 170121.6 €
Projet SYNERGINFO (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Recently, researchers have developed a new framework for decomposing the information that is shared by a number of variables, which characterizes public information that is shared by all the variables and private information that is contained only in specific elements. The main contribution of this work has been to distinguish between redundant and synergistic interdependencies: the former corresponds to variables that share the same information, while the latter refers to information sharing modes where the statistical dependency exists within the whole but not between the parts. The objective of this project is to analyze the relevance of synergistic modes of information sharing in different contexts, developing a deeper understanding of their nature and consequences. For this, the project has as specific goals (a) to further develop the theoretical framework for studying synergistic information sharing structures, and to use this framework to bring new light in important applications: (b) biometric databases and privacy due to its relevance for our modern society and (c) the study of brain activity due to its fascinating structure and function.

Mots clés : information theory, multivariate statistics, complex interactions, biometric databases, information theoretic causality

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet EDiMplant (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Recently, the demand for orthopaedic implants and devices has undertaken rapid growth due to the aging population and its global market is anticipated to reach $66.2B in 2023. To ensure the long-term survival of orthopaedic implants, it is urgent to tailor a multifunctional surface which would simultaneously have enhanced osteogenic and antibacterial properties. Therefore, the aim is to develop a competent surface modification technique which will promote improved osseointegration whilst retaining antimicrobial activity, thus ensuring the life-long performance of implants. A novel surface modification approach will be demonstrated using the specially designed tool electrodes in powder mixed electric discharge machining process for fabrication of modified surface layers exhibiting anti-bacterial and osteogenic characteristics. Exploiting world class facilities at University of Sheffield and a unique multidisciplinary framework; EDiMplant will reach the aim and strengthen the pillars of Horizon 2020. Supervisor(s) with world-leading experience, Dr Gwendolen Reilly, Dr Frederik Claeyssens, Dr Russell Goodall, and Dr Joanna Shepherd, will provide expert training and support to the Fellow in the essential skills inmaterial science, tissue engineering and infection biology, while, Dr Deepak Unune, leading Indian researcher, will bring expertise and novel application of electric discharge machining in surface modifications of implants to the host(s). The high-quality two-way transfer of knowledge required for this project will ensure the research goals of the highest quality are achieved, whilst also presenting a great opportunity to accelerate the academic career of the Fellow. Success would also lead to significant economic and societal impacts for the EU and worldwide, by aiding in the reduced incidence of orthopaedic implant failures.

Mots clés : electric discharge machining, anti bacteria, osseointegration, biomaterials

Participants :
- University of Sheffield (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet YIELDFACTOR (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Recently, the host lab found that a novel ubiquitin E3 ligase, SP1, regulates the translocon of the outer chloroplast membrane (TOC), which is responsible for importing nucleus-encoded proteins into plastids. SP1 achieves this by promoting the degradation TOC components by the cytosolic 26S proteasome. This is the first time the ubiquitin proteasome system (UPS) has been shown to directly regulate plastid development and function. By increasing or decreasing SP1 levels in transgenic Arabidopsis plants, multiple effects of SP1 were observed; e.g., inefficient de-etiolation leading to low survival rates and delayed leaf senescence in sp1 null mutants (Science 2012, 338:655-9). Also, sp1 mutants are significantly more sensitive to stress (unpublished). These data suggest that SP1 is important for the differentiation and interconversion of different plastid types, and all of the effects are highly correlated with plant growth and yield. Thus, discovery of SP1 strongly suggests potential applications in agriculture, such as delaying leaf senescence to produce a staygreen phenotype, or controlling amyloplast development during grain development, by modifying SP1 expression. This project will investigate the function of SP1 in cereals, and assess the potential of SP1 for manipulating plastids to improve cereal yield. I will generate transgenic plants with manipulated SP1 expression in Brachypodium distachyon (a versatile cereal model) and Oryza sativa (rice). I will study the development of plastids in the transformants, and assess the transformants for beneficial effects on yield parameters, such as starch content, seed weight, germination, de-etiolation, leaf senescence and stress resistance. At the end, I will have thoroughly assessed the potential use of SP1 for manipulating cereal traits linked to yield. A major strength of the proposal is the complementarity of my expertise with that of the host. Our unique combination of skills will ensure success of the project.

Mots clés : chloroplast, amyloplast, crop yield

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