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

African trypanosomes are parasites that cause disease in both humans and livestock throughout sub Saharan Africa, leading to death and hardship in afflicted regions. The disease is spread by blood-feeding tsetse flies and trypanosomes use sophisticated mechanisms to sense their environment in order to optimise their chances of transmission. In particular, whilst in the host bloodstream trypanosomes communicate with one another to monitor their own population density, this determining when they produce specialised transmission stages (so called ‘Stumpy’ forms). We have recently identified, using a genome-wide RNAi screen, components of the signal transduction pathway that drive this quorum sensing (QS) response. One component seems pivotal in the pathway- a molecule related to the YAK kinase of proteins. In yeasts and slime molds YAK kinase contributes to cell growth arrest in response to extracellular signals including nutrient limitation, whilst in mammals, related molecules of the DYRK family can also act in cellular quiescence. In this proposal we will investigate the function of trypanosome YAK kinase in the parasite's QS response. Specifically, we will investigate the kinase function in vitro and in vivo and dissect its action by following its location and targets. These are likely to differ from the situation in yeasts where YAK relocates to the nucleus and changes mRNA expression; in trypanosomes gene regulation is almost exclusively post transcriptional and likely operates within the cytoplasm. The function, location and interactions of YAK kinase in the QS signalling pathway is expected to provide comprehensive insight into how trypanosome parasites control their development in preparation for transmission, with additional important relevance for related parasites including other kinetoplastids and malaria. A two way benefit, encompassing training and expertise exchange between the researcher and host laboratory, will also be established.

Mots clés : trypanosoma, cell signalling, quorum sensing, protein kinase

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

African trypanosomiasis (AT), caused by the protozoan parasite Trypanosoma spp., is a debilitating disease that threatens millions of people in Sub-Saharan Africa. The human disease evolves in two stages, the second of which causes a fatal neurological infection if left untreated. The recent discovery of the orally-bioavailable drug fexinidazole, and its current use as a first-line treatment, has significantly improved disease outcomes associated with AT. However, the risk of resistance to fexinidazole treatment is a major concern that highlights the need for new treatment options. G-quadruplexes (G4s) are non-canonical DNA secondary structures that have recently emerged as an attractive target to fight AT. For example, recent studies have revealed the killing properties of a well-characterised G4-ligand, quarfloxin, against T. brucei parasites, showing the great potential for G4-targeting approaches to treat AT. However, the fundamental role of G4s in trypanosome biology and their validation as therapeutic targets have not been elucidated. In this proposal, I aim to unravel the biological functions of G4s in trypanosomes using integrated chemistry and genomic approaches. Specifically, peptide-based molecules designed to selectively target trypanosome G4s (TG4) will be developed and biophysically validated. The TG4-selective peptides will be used to functionally interrogate the trypanosome genome and to understand the effect of G4-modulation on gene expression using transcriptomics. Finally, our peptides will be engineered into fluorescent probes to facilitate real-time molecular visualisations of TG4s formation in vitro, and to provide an in-depth characterisation of these structures as novel targets to combat AT.

Mots clés : trypanosoma brucei, g quadruplexes, dna secondary structures, therapeutic target, african trypanosomiasis, peptides, genomics, transcriptomics

Participants :
- Imperial College London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet TIPPDECRA (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

After obtaining my PhD at the University of Utrecht in the Netherlands, I moved to San Diego for a 1-year postdoc at the La Jolla Institute for Allergy and Immunology. I now propose to move to Newcastle University in the United Kingdom to undertake a project on a new cell-based therapy for rheumatoid arthritis (RA), a destructive joint disease. This project is important since this new therapy could provide long-term benefit to RA patients. So far I have conducted all my work in mouse models. This project will enable me to acquire new expertise in human immunology and translational research. The host team at Newcastle University has developed a new immunotherapy for RA with tolerogenic dendritic cells (tolDC). These tolDC have been designed to switch-off destructive immune responses in the joint via the induction of regulatory T cells. The team has completed a phase I trial with tolDC in RA, and has found that the therapy is safe. However, in order to conduct a phase II efficacy trial, one crucial aspect of tolDC therapy must be improved: loading of tolDC with a relevant (auto)antigen so that they can induce antigen-specific regulatory T cells in the joint. However, selecting a suitable auto-antigen has been problematic. I propose that heat shock proteins (HSPs) are suitable antigens for loading of tolDC. HSPs are ubiquitously expressed in the rheumatoid synovium and pathogenic T-cell responses to these HSPs are found in RA patients. I hypothesise that by loading tolDC with exogenous synthetic peptides from HSPs, the pathogenic response can be suppressed through the induction of HSP-specific regulatory T cells. My project aims to i) establish a suitable HSP-peptide selection for tolDC-induced peptide-specific tolerance in RA patients and ii) test the therapeutic potential of HSP-peptide-loaded tolDC in a mouse arthritis model. A successful outcome of this work would form the basis of a new clinical trial with HSP-loaded tolDC in RA patients.

Mots clés : tolerogenic dendritic cells, rheumatoid arthritis, antigen presentation, heat shock proteins

Participants :
- Newcastle University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet TONEURENDO (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Ageing is recognized as one of the greatest social and economical challenges of the 21century for European societies. With, Vascular Cognitive Impairment (VCI) being one of the leading causes of age-related cognitive impairment and one of the major causes of disability in the elderly. Although, the concept of VCI was introduced in 1993, current treatment is limited to management of vascular risks and symptomatic pharmacotherapy targeting vascular dementia. The overall objective of this project is to fill the significant gap in early detection, prevention and treatment of VCI. This will be achieved by explaining microvascular mechanism of protective effects of thrombopoietin (TPO) in a novel unique mixed-risk animal model of VCI- specific to hypertension plus carotid-artery hypoperfusion (HH-VCI). Given increased number of progenitor endothelial cells after TPO treatment, it is hypothesizes that protective effect of TPO is mediated by endothelium. Furthermore, protective effect of TPO is expected to be caused by activation of neoangiogenesis, anti-inflammatory and vasoprotective mechanisms driven by TPO action on endothelial. This hypothesis will be tested in two stages first, in-vitro and second, in-vivo. In-vitro models, will be used to investigate endothelial response to TPO in terms of its modulation of inflammatory response angiogenic potential and vasoprotective mechanisms. In-vivo models of TPOR KO mice and HH-VCI mice will be used to validate and confirm mechanisms identified in in vitro stage of experiments.

Mots clés : vascular cognitive impairment  vci

Participants :
- Jagiellonian University (Pologne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 146462.4 €
Projet GLYCONEOBRAIN (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Ageing is the main correlate of dementia and several other neurodegenerative diseases which currently affect more than 6 million people in Europe. Molecular understanding of these brain conditions is important for their prevention and treatment. In mice, pathological granular structures positive for periodic acid-Schiff stain have been found in the hippocampus with increasing age. The degenerative process of granule formation appears to originate in astrocytes, but adjacent neuronal structures are affected and, accordingly, associated memory impairments have been described. Recent studies reported that granules express glycosidic neo-epitopes, a hallmark of the degenerative granule formation process. This neo-epitope has additionally been found in Lafora bodies of a mouse model of Lafora disease, a fatal neurodegenerative condition. On the other hand, mice serum contains natural IgM antibodies that recognise the glycosidic neo-epitope, suggesting a potentional removal mechanism. In this project, I aim to describe the structure of the glycosidic neo-epitopes of the hippocampal granules as well as the composition of the degenerative granules and Lafora bodies. To achieve these goals, I will employ a multidisciplinary approach exploiting glycomics and neurobiology, with the application of leading-edge technologies that include histological methods, analytical techniques, MALDI-MS imaging and laser-capture microdissection. Moreover, the binding patterns of the anti-neo-epitope natural IgMs will also be explored. Finally and importantly, the expression of the glycosidic neo-epitope in human brain will be assessed. Overall, the knowledge generated will provide new data on brain degenerative processes underlying age-related memory impairments in humans. Ultimately this project will generate new insights for the use of glycosidic neoepitopes as biomarkers for ageing and neurodegenerative diseases, and for prevention and therapeutic strategies using natural antibodies.

Mots clés : ageing, dementia, neo epitope, glycoconjugate, periodic acid schiff, lafora bodies, corpora amylacea, natural antibodies, hippocampus, maldi imaging, laser capture microdissection, biomarker

Participants :
- University of Liverpool (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet STRESSAGED (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Ageing-related diseases are the leading causes of morbidity and mortality. A ubiquitous and potentially preventable factor predisposing to their development is psychological stress, but the molecular mechanisms underlying this relation are largely unknown. This knowledge gap is addressed by the proposed project, which examines epigenetic modifications and, in particular, DNA methylation changes as molecular signatures that may be induced by lifetime stressors and act in concert with advancing age to shape disease risk. The proposed fellow will first identify the DNA methylation sites that are regulated by stressors and ageing and will then examine how these epigenomic sites determine gene expression and disease outcomes. Among key biological processes, the project will focus on immune dysregulation, a common pathogenic process for several diseases of the ageing. Immune dysregulation will be examined in the periphery but also in the brain, the orchestrator of behavioral, neuroendocrine and immune responses. The project will engage translational approaches using both human samples and animal models, implemented via collaborations among leading institutions and experts in Europe and USA. The applicant has unique interdisciplinary skills to carry out the project, including clinical background as well as experience in both clinical and basic research projects on the two fields brought together in the proposal, the biology of stress and ageing-related diseases. The impact of the project can be tremendous, since elucidating the molecular mechanisms of ageing-related diseases would contribute to the development of biomarkers, targeted prevention strategies and novel treatments for these devastating diseases.


Participants :
- Max Planck Society (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €
Projet DEMAIRPO (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Air pollution (AP) remains prevalent globally. Its impact on dementia risk is unclear. We propose to investigate the association of dementia with AP and explore mediation effects on the association from other factors. We will examine data of 2776 participants aged >=60 years who were randomly recruited from urban and rural of China. Their baseline risk factors (including environmental tobacco smoke-ETS and fish consumption) were recorded and dementia was diagnosed in a standard interview package. They were followed up for 4 years to identify mortality and incident dementia. We will calculate the residential distance proximity to major roadways (REDPMR) for each cohort member (an approximate AP exposure), and also collect regional AP monitoring data to evaluate individual exposure to AP. We will employ multivariate adjusted Cox regression models to examine the association of AP with dementia and interaction and mediation effects from ETS and fish consumption on the association. In the UK we will recruit 200 elders aged>=75 years with newly diagnosed dementia and 200 without dementia from the Royal Wolverhampton hospital. We will document their disease risk factors, REDPMR and local residential AP. Using multivariate logistic regression models we will examine the associations of REDPMR with dementia. We will run 2 focus groups each in the UK and China to explore the effects of AP on dementia and preventive measures of AP and dementia. Our unique data, including participants with special characteristics from China will offer internationally applicable insights into the impact of AP on dementia. Throughout the research project, use of varied study and research methodologies and rigorous training courses, our Fellow will develop his leadership skills and further his career in public health research. The project will strengthen a long-term collaboration between EU and China partners, and will provide Europe with new data to prevent dementia and to reduce AP.

Mots clés : air pollution, dementia

Participants :
- University of Wolverhampton (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet TASAB (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Algal-based biofuels are increasingly attracting attention as they have the capacity to serve both as a source of renewable carbon fuels and as a powerful tool for carbon sequestration. However, algal biofuel production remains outside the realm of economic feasibility due to the energy-intensive extraction techniques and limitations in algal cultivation which requires large amounts of fertilizer. Existing commercial algal biomass production technologies are prohibitively expensive for fuel generation which represents a commercial constraint to developing competitive European algal biofuel companies. The proposed Fellowship – TASAB - is a novel algal biorefinery concept, offering an environmentally-sustainable closed system integrating both thermal and biochemical conversion pathways. This concept will be able to maximize energy production from algae for achieving a net positive energy balance and to almost fully recycle nutrients to support algal large scale production and reduce the economic and environmental impacts associated with synthetic fertilizer use. TASAB will enhance and upgrade bio-oil yield and produce value-added products and biochemicals which could be sold at a premium and would offset production costs for energy generation. TASAB will enable this sector to produce cost-competitive biofuels, while creating a future-oriented sustainable economy. TASAB is a multidisciplinary project, enabling the Fellow to expand his research capabilities by undergoing intensive training in thermal processing at the EBRI (Birmingham, UK), algal biomass culturing techniques at the EBRI and Varicon Aqua Ltd (UK), anaerobic fermentation and electrolysis at LBE (France) and nutrient recovery at SOTON (UK). This training combined with his strong background in wastewater management will significantly expand his skill set, generating a highly valued researcher that will lead academia /industry in the promising European algal biorefinery sector.

Mots clés : algae, biorefinery, biofuels, pyrolysis, anaerobic digestion, electrolysis, ammonia stripping, struvite precipitation, biochar, biohydrogen, high value biochemical

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

Algebraic geometry is a sophisticated area of mathematics dating back to the mid 19th-century, that links algebra and geometry with many parts of mathematics and theoretical physics. The basic objects, called algebraic varieties, are the common zero sets of polynomial functions, which are higher dimensional analogues to the ellipses and hyperbolas of antiquity. The subject has key applications in very many branches of modern mathematics, science and technology. One of the main goals in algebraic geometry is to classify algebraic varieties. These can often be decomposed into simpler shapes that act as fundamental building blocks in the classification. But how many different shapes appear in each class of building blocks? Calabi-Yau varieties, characterised as flat from the point of view of Ricci curvature, are one of 3 types of building blocks of algebraic varieties. Calabi-Yau 3-folds and 4-folds have formed the focus of interest of string theorists over recent decades. A better understanding of the geometry and the classification of Calabi-Yau varieties would advance string theory in fundamental ways, and would provide many new examples and models to study. Since they are building blocks for constructions in geometry and theoretical physics, understanding how many Calabi-Yau varieties there are is a question of fundamental importance. The problem is to know whether the shapes of Calabi-Yau varieties come in just finitely many families in any fixed dimension - a property that goes under the name of boundedness. This very difficult question remains wide open. While this problem has long been considered to be out of reach, recent developments make powerful techniques available to investigate new aspects of it. The aim of this research project is to show that there is essentially a finite number of families of Calabi-Yau varieties with some extra piece of structure -- an elliptic fibration -- in any dimension.

Mots clés : birational geometry, minimal model program, boundedness problems, calabi yau varieties, fano varieties, moduli spaces, k stability, elliptic fibrations, canonical bundle formula

Participants :
- Board of the Swiss Federal Institutes of Technology (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191149.44 €
Projet REFINE (Horizon Europe, appel à projets 2022)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Electronic products are progressively smaller and more powerful, resulting to an exponential increase in the generated residual heat. Their effective and environmental-friendly cooling is therefore, of upmost importance for many applications such as Data Centres, Fuel Cells, Insulated-Gate Bipolar Transistors, Lithium-Ion Batteries and Photovoltaic Cells, with a market value of several billions of dollars worldwide. Flow Boiling within micro-passages has been proven as one of the most efficient cooling strategies for such High-Power Density Electronics. However, such solutions, are not yet commercially available. This is due to a lack of a deep understanding of the underpinned flow and transport processes and unresolved ambiguities in micro-scales and hence, of reliable and easy-to-use thermal design tools for small-scale components. REFINE aims to give light at such crucial ambiguities, utilising a synergic combination of novel Volume Of Fluid (VOF) based numerical simulations and tailored high-resolution experimental diagnostics. Dr Andredaki will develop a novel cutting-edge simulation tool starting from an already enhanced VOF solver that she has been developing in the last years. This will be validated against parallel advanced experimental measurements on flow boiling, that she will perform using single and multiple parallel micro-channel heat sinks. The final optimised and validated numerical solver will then be applied for a wide series of parametric simulations that in combination with additional laboratory measurements will form a unique database that will lead to the development of novel, physics-based design correlations for flow boiling micro-channel heat sinks. The word-leading expertise of Prof. Moreira, who will supervise this project, on the experimental techniques for microscale boiling, guarantees the highest level of knowledge transfer, enabling Dr Andredaki to further develop her skills and enhance her future career opportunities in academia.

Mots clés : flow boiling, phase change heat transfer, micro channel heat sinks, numerical simulations, volume of fluid method, spatiotemporally resolved experimental diagnostics

Participants :
- Université de Lisbonne (Portugal) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172618.56 €
Projet WoPressRep (Horizon Europe, appel à projets 2024)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

The general objective of this research project is to recover and analyze, both quantitatively and qualitatively, the female contribution to the debates and transmission of republican and democratic principles, values, and projects between 1900 and 1914 through their journalistic activity, adopting a plurinational geographical approach that includes three Atlantic countries: Portugal, Mexico, and Spain. The adoption of this Atlantic approach not only allows for the appreciation of the possible circulation of ideas and the mobility of some of their spokespersons within these territories but also overcomes the limitations sometimes imposed by national frameworks and provides insight into how women participated in the broader debate on republicanism and democracy taking place at the time.

Mots clés : republicanism, democracy, atlantic history, circulation of ideas and proyects

Participants :
- College of Mexico (Mexique) — Partner, associated partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Université de Lisbonne (Portugal) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191343.12 €