Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet DC cancer (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Dendritic cells (DC) are powerful antigen-presenting cells that can induce antigen-specific adaptive immunity to pathogens but also protective immunity against transformed self, i.e. cancer. This crucial role of DC makes them an attractive target in cancer vaccination. However, DC can also negatively regulate immunity by inducing antigen-specific tolerance and are a target in immunomodulatory approaches aimed at dampening autoimmunity or allergy. Given this dual role in immunity and tolerance it is hard to predict what would happen if DC were to become neoplastically transformed. Their immunogenic potential could make transformed DC highly susceptible to control by the immune system, which might explain why DC cancers are rarely observed in humans. In contrast, their tolerogenic potential could make transformed DC especially adept at escaping immunological control. So far, the aetiology of DC cancer and its immunological consequences remain elusive due to the lack of appropriate models to study the disease. In order to investigate the feasibility of DC tumour formation and the immune control of DC tumours, a novel genetically-engineered mouse model of DC cancer has been generated. We will use this model to characterise DC tumour development in vivo and establish which DC subsets contribute to DC cancer. Furthermore, we will adapt this model so that we can control the location and onset of neoplastic transformation of DC in vivo. Both models will then be employed to investigate to which extent DC cancer is recognised and modulated by cells of the immune system. Furthermore, we will assess whether transformed DC exploit tolerogenic mechanisms to progress into tumours. Our proposal will give novel insights into the biology of cancer development and its control by the immune system. We anticipate that understanding these processes will provide important insights into immune surveillance and the role of DC in anti-cancer immunity, helping to improve cancer immunotherapy.

Mots clés : dendritic cells, cancer, histiocytosis, anti tumour immunity, tumour immunogenicity

Participants :
- Cancer Research UK (Royaume-Uni) — Partner, beneficiary, Recherche, subvention : 0.0 €
- The Francis Crick Institute (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 183454.8 €
Projet DENGUE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Dengue is a mosquito-borne illness for which approximately half of the world’s population is at risk, with close to 100 million symptomatic cases per year. Classified as a Neglected Tropical Disease (NTD) that disproportionately affects the world’s most vulnerable populations, basic and translational research regarding the cellular consequences of Dengue virus (DENV) infection is vastly under-represented. Even fewer studies examine the neuro-immunological manifestations of severe dengue which embodies the most fatal and dangerous form of disease. However, as the central nervous system (CNS) is inaccessible in humans with the rare exceptions of post-mortem brain tissue, the lack of appropriate human models and platforms to test large-scale functional perturbations have hindered efforts to conduct human studies in the context of DENV infection. Here, we propose to develop an autologous human model that represents the DENV neuro-immune interface by employing a two-step reprogramming method that differentiates donor blood to derive donor-matched induced neuronal cells (iNs) via induced pluripotent stem cells (iPSCs).We will then establish a DENV infection paradigm of both neural and immune lineage cells, and systematically screen for potential neuro- and immune-modulators of DENV pathogenicity and cell-cell interactions. High-content image-based profiling and convolutional neural networks (CNNs) will be implemented to untangle the contributions of different cell types and learn heterogeneous cell-type-specific or donor-specific phenotypes. Finally, for promising candidate modulators that either affect cellular DENV pathogenicity, those that alter the baseline neuro-immune interactions, or those in which the drug response differs among donors - we will conduct matched transcriptomic profiling to uncover functional gene networks that regulate features of DENV-mediated perturbation of neuro-immune homeostasis.


Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191149.44 €
Projet Cytokineproteomics (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Deregulation of pro-inflammatory cytokine signalling is the underlying cause for many inflammatory diseases. Thus, understanding the molecular mechanism of cytokine signalling is necessary to develop suitable therapies. The enormous complexity of cytokine cascades has however impeded the development of new therapies. To shed more light into these intertwined signaling cascades, I plan to use a proteomics approach that allows the identification of signalling mechanisms in a multi-dimensional and unbiased fashion. The recent development of the EasyPhos protocol in the Mann laboratory will allow me to take an unprecedented look at phosphorylation events occurring in cells stimulated by single and by combinations of disease relevant cytokines. Simultaneously I will be able to detect changes in the ubiquitinome using the di-Gly enrichment strategy. By combining phosphoproteomics and ubiquitin proteomics with the CRISPR/Cas9 technology to delete and modify members of diverse signaling pathways, I will be able to analyze the role of these players and their post translational modifications in the respective signalling pathways. This study will therefore investigate the mechanisms and the relationship between phosphorylation and ubiquitylation in cytokine signalling in an unprecedented way and has the potential to result in the identification of new therapeutic strategies for the treatment of a range of inflammatory diseases.

Mots clés : mass spectrometry, cytokine, phosphorylation, crispr technology

Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €
Projet ReKnow (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Descriptive and empirical sciences, such as History, Archaeology, Biodiversity, and Cultural Heritage, are the sciences that collect, observe and describe phenomena in order to explain them and draw interpretative conclusions about their behaviour and their relationships under given circumstances. Researchers in these sciences usually encounter problems related to the integration of data coming from different sources, the epistemological adaptation and refinement of their research under specific circumstances, the usability of their data analysis methods and tools, and the transparency and reliability of their research processes and results. The ReKnow project aims to support researchers in descriptive and empirical sciences to better handle these problems by providing models, algorithms and tools that allow for better documentation, analysis and exploration of research processes and data. This will be achieved by combining i) the expertise of the host institution in cultural informatics, its strong background in conceptual modeling and argumentation theory, and its long-standing collaboration with a large number of organisations in descriptive and empirical sciences, ii) a set of training activities that will provide the principal researcher with the required disciplinary and interdisciplinary background to achieve the project objectives and which complement his current expertise in semantic web technologies, exploratory search, and data mining, and iii) the close collaboration with two History projects and a research institute dedicated to the study of the history of science, that provide requirements, use cases and data as well as the opportunity to directly apply the ReKnow results in real scenarios.

Mots clés : cultural informatics, conceptual modeling, argumentation and reasoning, metascience, descriptive sciences, empirical sciences

Participants :
- Foundation for Research and Technology Hellas (Grèce) — Coordinator, beneficiary, Recherche, subvention : 165085.44 €
Projet TS4NC (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Despite enormous research efforts across academia and pharmaceutical industry, all clinical trials over the last decade have failed in finding a treatment for Alzheimer’s Disease (AD) which remains one of the greatest challenges in drug discovery. Taking consideration all together three prevailing AD hypotheses: Amyloid Cascade, Metal Ions and Oxidative Stress, researchers conclude that loss of neurons is due to a high level of oxidative stress produced by nonregulated redox active metal ions such as copper linked to different forms/aggregates of amyloid-β (Aβ) peptides. Therefore, the regulation of metal homeostasis is a key target for drug development. Herein, we propose a new class of multifunctional agents – S4Ns, which not only sequester Cu ions from their Aβ complexes and arrest their redox cycles, thus reduce oxidative stress in the neuronal cells, inhibit Aβ aggregation, inhibit neuroglia activation and provide anti-inflammatory effects, delivering overall neuroprotection, but also put Cu back into normal physiological circulation by releasing Cu to natural Cu-carriers. The key novelty of this approach lies in that S4N mimics the N-terminus of Aβ4-x peptide (ATCUN motif), providing 4N square planar Cu(II) coordination with high affinity and selectivity. In general, S4Ns do not act as traditional chelating agents by simply eliminating metals from the organism, on the contrary they perform as Metal–Protein Attenuating Compounds (MPACs) by redistributing and assisting in the restoration of brain biometal homeostasis. This synergistic but novel strategy will allow us to carry out a comprehensive study of the new compounds and shed light into discovering promising drug candidate. Of equally importance, TS4NC MCSA will open new research horizons and significantly boost scientific career of the applicant, by helping her to reach professional maturity during the fellowship.

Mots clés : amyloid beta, alzheimer s disease, copper homeostasis, chelation, therapeutics, ros production, aggregation

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet DESIQM (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Despite intense research activity, most new superconductors are discovered by chance, rather than by deliberate design. Consequently, they have limited tunability, which has plagued progress towards a room-temperature demonstration. In particular, electron interactions are extremely challenging to tune, but are assumed to be vital in most high-temperature superconductors. Here I introduce a new paradigm for the bottom-up fabrication of custom-designed superconductors, called interacting quantum metamaterials. These metamaterials are precisely constructed, one atom at a time, using a scanning tunneling microscope. They inherit tunable, strong electron interactions from their unique substrate: a topological Kondo insulator (TKI). A TKI substrate neatly overcomes the two impediments for interacting quantum metamaterials: it hosts quasiparticles that move slow enough to interact with one another, and it is a true topological bulk insulator, which electrically confines these quasiparticles to the surface, where they are easily accessed and manipulated. By rearranging surface atoms, I will create metamaterial geometries that localize these novel TKI surface quasiparticles in order to mimic the parent state of many high-temperature superconductors, a Mott-like insulator. Then, I will adjust the electron concentration by tip-induced electrostatic gating and behold the onset of superconductivity in a fully tunable experimental platform. These results will open a new path to room-temperature superconductors, leading to highly efficient power transmission and storage, which can reduce CO2 emissions and slow climate change.

Mots clés : topological kondo insulator, atom manipulation, metamaterials

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet SPArKLE (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Despite major advances in the development of novel immunomodulatory drugs, the incidence of many immune disorders such as allergic and autoimmune diseases is increasing worldwide, particularly in Western countries. Innovative therapeutic targets must be identified to limit the social and economical impact of such pathologies, and a better understanding of the pathways involved in immune cell activation and functionality is needed. The SPArKLE action will provide an outstanding training programme to an experienced researcher (ER) in the research area of immunometabolism, a novel exciting frontier in immunity and inflammation, which investigates the importance of intracellular metabolic modulation in immune cell functions. By using a multidisciplinary approach spanning from basic biochemistry to immunology and in vivo studies, the goal of the SPArKLE research activity will be to evaluate the role of the metabolite succinate and of the enzyme pyruvate kinase (PK) in the effector functions of CD4+ T lymphocytes and in the development of autoimmune and allergic diseases. Succinate and PK where recently identified as key players in immune cell-mediated inflammation, but their involvement in the activation and functionality of T cells have never been investigated thus far. This research project may identify a T cell-specific role for succinate and PK, the targeting of which could have therapeutic utility in inflammatory and autoimmune diseases. The SPArKLE fellowship will also allow the ER to strengthen transferable skills such as communication/dissemination of results, mentoring and scientific writing, and to acquire novel competences in terms of results exploitation, entrepreneurship and project coordination. Overall, the SPArKLE training programme will expand the ER scientific background and interests and his employability and leadership potential, with the final goal to help him start an independent research career in an academic or non-academic institution.

Mots clés : immunometabolism, t cell immunity, succinate, pyruvate kinase, neuroinflammation, allergy

Participants :
- Trinity College Dublin (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 125244.0 €
Projet GOLDEN (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Despite recent advances in cancer therapy, many challenges remain to reduce the systemic adverse effects of antineoplastic therapeutics. A major goal in the field is to make nanomedical devices that could bypass the metabolic machinery of cells and perform tasks that are not possible with biological entities, such as the manufacture of bioactive molecules at specific locations in a continuous, atomically precise manner. The use of metallic nanoparticles (NPs) as biocompatible catalysts provides the opportunity to carry out abiotic catalysis inside cancer cells or tissues. Such bioorthogonal reactivity opens up new unprecedented ways of mediating artificial transformations in complex biological systems. Solid supported Au-NPs have recently demonstrated a novel, very promising role as heterogeneous catalysts able to generate bioactive compounds in biological environments. Herein I propose an innovative approach to develop catalytically- active Au-NPs immobilized within implants or "protected" under self-assembling monolayers to enable the activation of systemically-administered bioactive precursors at specific locations via novel Au-mediated deprotection chemistry. To confirm the in vivo functional capabilities of the devices, I will test the capacity of the novel devices to activate dyes and neuromodulators in the brain of zebrafish. This highly innovative multidisciplinary approach could offer a unique and safe method to release bioactive molecules in exact anatomical locations for the treatment of localized disorders including cancer or chronic pain and, in doing so, promote Scientific Excellence in Europe. As the recipient of the advanced training required to perform such a novel programme of research and developer of such tools, at the end of this fellowship I will reach a privileged position for establishing myself as an independent researcher and starting cross-disciplinary collaborations with academics and Pharma across Europe.

Mots clés : gold catalysts, bioorthogonal catalysis, heterogeneous catalysis, bioinspired nanostructures, self assembled monolayers, prodrug therapy

Participants :
- University of Edinburgh (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet SMPSBN (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Despite the importance of post-translational variation to the function of proteins in a living organism, sequencing proteins to study these variations is still a costly and time-consuming process, with intrinsic limitations. Protein sequencing and detection of post-translational modifications (PTMs) by mass spectrometry, the current gold standard, requires extensive sample preparation and large sample sizes, and possesses a limited dynamic range with respect to sample concentration. These limitations severely restrict its application to biological and clinical problems. A robust method for sequencing proteins and detecting PTMs at the single-molecule level would be revolutionary for proteomics research, allowing biologists to quantify low-abundance proteins as well as distributions and correlations of PTM patterns, all at a single-cell level. I propose a first-of-kind method for protein sequencing with applications in fundamental biology, cancer immunotherapy, and pharmaceutical development. This method uses biological nanopores in a manner similar to nanopore DNA sequencing, an established single-molecule sequencing technology capable of high throughput and single-molecule sensitivity. Developing this method for protein sequencing comes with many significant challenges, which will be addressed over the course of the proposed research.

Mots clés : protein sequencing, nanopore physics

Participants :
- Delft University of Technology (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187572.48 €
Projet SPERMAGE (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Deterioration in sperm quality with age is a major cause of male infertility. This has particular socio-economic relevance for Europe where fatherhood is increasingly delayed and infertility has reached near epidemic levels, costing the EU €4 billion per annum. The mechanisms causing, and the full consequences of declining sperm quality with age remain very poorly understood. For example, it is unclear how much of the reduction in sperm quality is due to advanced male age or the time sperm are stored within males reproductive organs, and we do not understand the mechanisms responsible for deteriorating sperm quality with increasing male age. The general aim of this project is to disentangle the effects of male aging and sperm aging on sperm quality, fertility and reproductive fitness using Drosophila melanogaster as a model. We will also test putative mechanisms thought to cause age-related fertility declines and test two possible general pathways through which sperm age. This proposal is a much needed integration of evolutionary ecology and sperm physiology, benefiting from the ideal match of skills and expertise of the Applicant (Tourmente - physiology), and the PI (Hosken - evolution). Since the mechanisms and phenomena studied are conserved across animals, the research proposed has high potential to produce results relevant to fundamental and applied research in human aging and reproductive health and animal breeding. The MSC fellowship will be pivotal for Applicants development toward independent research and offers the unique opportunity to work in one of the most prominent evolutionary ecology groups worldwide. The Biosciences Department at the University of Exeter is world-leading and provides excellent opportunities for the personal career development of the Applicant, who in turn brings novel skills to Exeter that will greatly benefit this group.

Mots clés : sperm quality, aging, fertility, sperm function, iis pathway, reproductive fitness, cellular metabolism, gene expression

Participants :
- University of Exeter (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet SHARP (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Determining the temporal relationships of large-scale atmospheric and oceanic fluctuations is crucial for advancing understanding of the mechanisms controlling heat transfer between the Northern and Southern Hemispheres. The thermal bipolar see-saw caused asynchronous interhemispheric climatic changes during the last glacial period and Southern Ocean marine records and the Antarctic ice-cores are valuable archives recording this past climatic variability. Ascertaining the precise phasing of the climatic variability between these records provides crucial boundary conditions for testing models simulating the future behaviour of the bipolar see-saw and assessing potential large-scale oceanic and atmospheric reorganisations under anthropogenic forcing. In addition, establishing tighter constraints on phase relationships between sedimentary evidence for deep-water ventilation of CO2, and ice-core evidence for past atmospheric CO2 variations is key to determining the future response of the Earth system to rising CO2 levels. This project will address this challenge by ascertaining the rate, timing and phasing of Southern Hemisphere climatic changes between 40-10 kyr BP using tephrochronology to independently synchronise the palaeoclimatic sequences using common horizons of volcanic ash as time-synchronous tie-lines. Recognition of ash horizons not visible upon core inspection (cryptotephras) within sequences increasingly distal from volcanic regions has increased the scope of this technique. Cryptotephra identification methods will be used to trace ash horizons visible in Antarctic ice-cores into a marine core network from the Southern Ocean Atlantic sector and to trace previously unknown horizons identified in the marine realm into the Antarctic Atlantic sector EPICA DML ice-core. This region has a high potential for synchronisation due to the number of upwind volcanic regions that have previously deposited volcanic ash over the ice-sheet and Southern Ocean.

Mots clés : tephrochronology, palaeoclimate reconstruction, southern ocean, bipolar see saw

Participants :
- University of Bern (Suisse) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Cardiff University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 267147.0 €