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

Local communities in Columbia are lacking access to safe drinking water, principally due to mercury pollution and pathogens. Circumstances are such that access to a well-managed piped water supply system are not possible and therefore the communities require local low-cost point-of-use treatment. The objectives of the adsorbing Filters for REmoving pathogenS and Heavy metals in WATER project (FRESHWATER) are: (i) to cocreate/codesign with local community members in deprived areas in Colombia adsorbing filters, sourcing local plant and other materials as feedstock; (ii) to integrate these into adsorbing filters creating a robust and reliable water filtration system able to produce safe and clean drinking water, monitored by easy-to-use and easy-to-read quality control mechanisms, and (iii) to develop a two-way working relationship with a “community champion” to outlast the duration of the project. Using the engineering skills and knowledge of the Experienced Researcher and the host supervisory team at the University of Bath, UK, the project will lead to improve the quality of the water in low-income communities as well as in humanitarian crises, thus lowering the burden of waterborne diseases. This approach will be adoptable in a wider context in other poor communities in Latin America, Africa and Asia. To cocreate/codesign the adsorbent, frequent field studies in one low-income community in Colombia will be undertaken during the project, in partnership with the Universidad Nacional de Colombia in Bogota.

Mots clés : drinking water, adsorbing filters, heavy metals, pathogens, cocreation, local and renewable plants and materials, water analysis, integration in renewably powered water filtration units

Participants :
- University of Bath (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet STRESS-Mums (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Lone motherhood is considered as an increasing social problem, not only because its increase but also since it leads to diverse and separated women having only a partial citizenship. There is little knowledge on the social relations and practices that contribute – or do not contribute – to protecting and socially including lone mothers, beginning from the crucial transition to lone parenthood: the judicial evaluation. Focusing on the transition from double parenthood to lone motherhood and, in particular, on the period of judicial evaluation for child custody and judicial decisions for children/family allowances and divorce/separation, this project aims to investigate some specific aspects of the socio-cultural construction of an active gender citizenship by future lone mothers. The interest is in lone mothers’ everyday strategies and social practices to claim inclusion and to negotiate (or not negotiate) the dominant definition of family and parenthood proposed by institutions and professionals, and the less legitimated and multiple situated definitions of lone parents and their families. Introducing the everyday dimension into the study of gender citizenship has the purpose of exploring the lone mothers’ manifest and hidden ‘work’ of legitimation and of possible de-legitimation by institutions. Adopting the sociological approach of Institutional Ethnography (IE) as a method, this study will collect data in three EU countries (Belgium, Italy and Spain) and in the UK, with discursive interviews to lone mothers, professionals and gender issues activists, participant observations, and photo-voice. The action includes an extensive training in life course studies and gender studies, advanced qualitative methods and academic English language. This action will be hosted by the University of Antwerp, with a secondment phase at the University of Edinburgh and visits at the University of Granada and at the IEN-Institutional Ethnography Nordic Network.

Mots clés : lone mothers, gender citizenship, active citizenship, advocacy, everyday life sociology, institutional ethnography

Participants :
- University of Antwerp (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178320.0 €
Projet PolyCRomA (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

Long neglected, the polychromy of ancient statues has been increasingly studied during the last 20 years with a multidisciplinary cooperation between humanities and natural sciences. If the use of colour seems omnipresent in Greek statues with an illusionistic aim, the phenomenon is not only understudied in Roman statues but also more ambiguous: the fashion for copying Greek statues seems to develop the taste for marble and the socio-political value of the statues could be reflected in the use of colour. This action explores the meaning of Roman Imperial statues polychromy in Proconsular Africa though the Bardo museum collection in Tunisia, proposing the first systematic study of the use of colour in the statuary of an important Imperial province. The variety of typology, quality and provenance (local, Asia Minor, Rome workshops) of the more than 100 coloured statues in the corpus offers a significant mirror of the African society. Moreover, as the archaeological context of discovery is well known, the meaning of the polychromy will be analysed in relation with the socio-political and religious purpose with which these artefacts were conceived. The preserved traces of colour will first be documented by coupling visual investigation (by the support of multispectral imaging and UV and VIL videomicroscope) and in-situ analyses (XRF and µRaman) in order to identify the techniques used to colour the statues. Selected micro-samples will undergo further quantitative analyses (PIXE, SEM/EDX, hyperspectral imaging, FT-IR). Finally literary and epigraphic sources of Proconsular Africa mentioning the colour of statues will be inventoried and the use of colour on the statues will be compared with their counterparts in painting and mosaic. The overall evaluation of the data will go beyond the scope of the province and will reach wider conclusions on the variations in the use of colour and its meaning, contributing to the history of colour and the modern perception of Roman art.

Mots clés : tunisia, roman africa, statues, polychromy, pigments, visual aesthetic, painting

Participants :
- University of Liège (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178320.0 €
Projet Pept-AGE (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Loss of muscle function through advancing age, injury or disease significantly decreases both the quality of life and life expectancy of millions of individuals globally. Treatments tackling this issue have proven elusive as in vitro systems aimed at modelling age-related muscle atrophy are primarily murine based and fail to capture the complexity of this process in humans. In particular, these models neglect to accurately account for the impact of cellular-ageing and senescence on the advancement of sarcopenia-induced muscle wastage. This project aims to address these problems by firstly developing a more human aligned in vitro ageing model to elucidate key pathways associated with muscle loss. From this in vitro model, we will identify key mechanistic pathways driving age-related muscle loss at the transcriptional and translational level. Supplied with suitable data, artificial intelligence (AI) has to potential to rapidly accelerate the discovery of novel therapeutics. As such, here, informed by data derived from the human in vitro model, Nuritas’ proven artificial intelligence platform will be applied to identify novel bioactive peptides that have the potential to counter the impact of cellular aging thus ameliorating muscle loss. This innovative proposal affords the experienced researcher the opportunity to bring his knowledge at the forefront of ageing research back to Europe and combine it with the expertise of an industry leader in AI therapeutic discovery, facilitating decisive two-way intersectoral transfer of knowledge. By integrating these distinct interdisciplinary skillsets this project has the expected outcomes of discovering more clinically relevant, translational models and therapeutics for muscle wastage disorders.

Mots clés : ageing, sarcopenia, cachexia, artificial intelligence, peptides, drug development, muscle, autophagy, metabolism, in vitro, assay development, bioactive, cellular senescence

Participants :
- Nuritas (Ireland) (Irlande) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 196590.72 €
Projet AAT-NAA (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Low temperature thermochronometry (LTT) dating is a powerful tool in geoscience, used worldwide, to provide unique information on the thermal history of rocks. Using these insights geologists can achieve a better understanding of geological processes that have occurred over million year timescales even in settings where erosion has removed much of the geological record. Despite the success of these techniques in tackling geological problems, there still exists a major gap in our knowledge over the fundamental principles that underlie these dating systems. Much of this uncertainty stems from an incomplete understanding of inter and intra-crystal compositional variation and the influence this has on the kinetics of the dating system. Reaching a complete understanding of crustal thermal histories also remains a major challenge as the lowest temperature thermochronometers, apatite fission track (AFT) and apatite (U-Th)/He (AHe), are only sensitive over a temperature range of c. 120 – 40°C. The lower temperature limit of this range is also dependant on apatites having low degrees of radiation damage that can enhance retention of He within apatite. This project will advance AFT and AHe methodology by focusing on apatites enriched in U and Th from geological settings considered stable. The first goal is to obtain detailed REE compositional analysis using LA-ICP-MS to refine fission track annealing models and obtain high precision measurements of parent elements to improve AFT age data. The second goal is to ensure that the maximum amount of thermal history information is extract from the 4He concentration profile in the apatite crystal. This will be achieved by a combination of 4He/3He analysis and multi-single-grain AHe analysis of broken apatite crystals. By achieving these two goals the project will advance methodology, establish analytical capabilities at the host organisation and provide new insights into the thermal history of the crust at stable geological settings.

Mots clés : low temperature thermochronology, isotope geology, tectonics, landscape evolution, geochronology, geochemistry, la icp ms, 3he analysis

Participants :
- Université de Rennes (France) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 173076.0 €
Projet HDAC6_GEMM (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Lung cancer is a leading cause of cancer deaths in Europe. Non small cell lung cancer (NSCLC) accounts for nearly 85% of all cases of lung cancer with a five year survival rate of 15%. Novel targeted therapies are urgently needed to overcome drug resistance and prevent tumour recurrence. The host supervisor carried out a small molecule screen to identify therapeutics for the treatment of drug-resistant NSCLC. A novel specific inhibitor of histone deacetylase 6 (HDAC6) was discovered. The molecular mechanisms of HDAC6's role in cancer is beginning to be elucidated however, this task is made difficult due to the lack of a specific inhibitor. The overall research aim of this proposal is to understand the molecular mechanisms of HDAC6 in the tumour initiation and progression of NSCLC. To do this, I will develop a unique state-of-the-art conditional genetic mouse model of NSCLC in which HDAC6 is knocked out. I will do this work in the laboratory of Prof. Wong at New York University, an expert in conditional genetic mouse models. I will study the role of HDAC6 on the immune-microenvironment of the lung tumours using multi-parameter flow cytometry and single cell RNA-sequencing. Upon re-integration to the host laboratory I will establish the HDAC6 knockout NSCLC mouse model. Lastly, I will assess the efficacy of the novel HDAC6 inhibitor on tumour progression compared to the mouse model. This project has the potential to contribute greatly to our understanding of the role of HDAC6 in NSCLC and lead to the discovery of targeted therapeutic. Through this prestigious fellowship I will diversify my research skill-set, I will gain international experience in a world-leading laboratory of NSCLC and I will be excellently positioned to develop my independent research career on return to Europe.

Mots clés : conditional genetic mouse models, cell ceath, tumour microenvironment, hdacs

Participants :
- Royal College of Surgeons in Ireland (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 248063.4 €
- New York University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet PrecTherLSCC (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Lung squamous cell carcinoma (LSCC) represents one third of lung tumours; 550,000 cases are diagnosed annually worldwide (20% occur in Europe). Treatment options for this cancer type are still scarce. Identification of LSCC genetic drivers is thus an essential unmet need for developing novel therapies for this disease. In a stepwise multidisciplinary approach, we will determine if TNIK (Traf-2 and Nck-interacting kinase), a gene amplified in almost 40% of LSCC cases, constitutes a therapeutic target for the treatment of LSCC patients. Our preliminary data show that TNIK is overexpressed in LSCC cells, in which it has a pro-oncogenic role. Using proteomics approaches and functional assays, we will define the molecular mechanisms and critical signalling pathways that TNIK modulates to promote LSCC progression. In xenograft models we will confirm the contribution of TNIK to the studied phenotypes in vivo. We will analyse TNIK levels and activity (after identification of substrates) in patient samples, and will aim to validate TNIK as a target for therapeutic intervention using small molecule TNIK inhibitors in novel preclinical models: LSCC organoids and patient-derived xenografts. Finally, we will assess if increased TNIK expression can serve as a biomarker to select patients that would benefit from treatment with TNIK inhibitors. Our studies will increase our knowledge on LSCC biology and aim to find a precise treatment for this disease. This project will enable Dr P Torres-Ayuso to develop a wide range of new and transferable skills, and will allow him to broaden his technical, mentoring, management and communication skills. He will benefit from the high calibre of the Cancer Research UK Manchester Institute, and the expertise of his supervisor (Dr J Brognard) who will aid in his development as a young scientist. This project will thus enable the Fellow to achieve his long-term objective of obtaining a leadership position in a competitive European Institute.

Mots clés : lung squamous cell carcinoma, targeted therapies, driver genes, protein kinases, cell signalling

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

Lysine acetylation is a key protein post-translational modification (PTM) found throughout the cellular environment and across the range of species. This PTM is dynamic, with histone acetyl transferases (HATs) acetylating lysine, and histone deacetlyases (HDACs) reversing the modification. In addition, proteins modules bromodomains, have been identified that bind to acetylated lysine (KAc) and mediate protein-protein interactions. In humans, bromodomains exist as part of larger proteins, many of which are involved in transcriptional regulation. Bromodomains contain a KAc-binding pocket for which small molecule ligands have been identified. These ligands prevent the interaction of bromodomains with KAc and have been invaluable in dissecting the fundamental biology mediated by bromodomain-containing proteins (BCPs). We and others have developed potent ligands for the human bromodomain and extra C-terminal domain (BET) bromodomains. These compounds have antiproliferative effects in cancer cells lines and modulate inflammation and atherosclerosis. This work led to an explosion of interest in developing BET bromodomain inhibitors, resulting in 5 compounds in clinical trials. Despite rapid progress in understanding the role of human bromodomains, their function in other species is poorly understood. Given the fundamental role played by bromodomains in humans, we hypothesise that BCPs will play equally important roles in other organisms. To understand the role of non-human bromodomains we will develop small molecule probes to study the function of BCPs in the parasite Trypanosoma cruzi. We have selected T. cruzi for two reasons: 1. Four BCPs (TcBDF1-4) have been discovered in T. cruzi; our collaborator Prof. Serra has cloned these proteins and we have the plasmids; 2. T. cruzi is the parasite that causes Chagas Disease and hence bromodomain ligands might ultimately represent a novel method of treatment for this disease.

Mots clés : epigenetics, parasites, chagas disease, inhibitors, bromodomains, medicinal chemistry

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet GlycoPCs (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Lysosomal storage disorders (LSDs) are a group of 50 rare inherited metabolic disorders that in many cases originate from mutations that destabilise glycosidase 3D folding precluding its transportation to the lysosomes, which leads to substrate accumulation at the lysosomes and cellular dysfunction, with severe symptoms. An emerging therapeutic approach employs small molecules, called pharmacological chaperones (PCs). PCs bind and stabilize the folding of mutant lysosomal enzymes, allowing proper cellular translocation to the lysosome, reducing substrate accumulation. However, there is still no drug already on the market based on this concept and the PCs discovered until now lack the necessary effectiveness to replace other therapies. One important reason is that the complex mechanisms underpinning the enzyme stabilization operated by chaperones are poorly understood in structural terms and currently under debate. Understanding the mechanism will provide more rational criteria and guiding principles for the design of improved PC drugs. In this proposal we are interested in providing novel structural approaches to understand the mechanism of action of new PCs for efficient treatment in Gaucher and Fabry diseases, as two of the more prevalent LSDs. We will develop a powerful high-resolution combined protocol including mass spectrometry (MS) and nuclear magnetic resonance (NMR) to: (i) provide a novel methodological approach for the discovery of PCs, (ii) apply the novel protocol to a small library of promising new ligands, and (iii) deepen our understanding of the mechanism of action of PCs in structural terms by combining the novel MS/NMR protocol with very long molecular dynamics simulations of wild-type and mutant glycosidases. Besides the potential for high-impact of the project, it will also allow the experienced researcher, Dr E.Casal, to be trained in a wide range of new skills, adding to her strong previous experience in MS.

Mots clés : protein carbohydrate interactions, nmr spectrosocopy, pharmacological chaperones, molecular, dynamics, glycosidase inhibitors

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

MACROIMAGING is a highly interdisciplinary project encompassing the preparation and optimisation of innovative fluorogenic imaging tools with high selectivity for metastasis-associated macrophages. The metastatic potential of tumours is defined by the tumour microenvironment (TM), where macrophages are the most abundant cells. However, the role of macrophages in the TM remains elusive mainly because of the lack of technologies to target these unique populations of cells in vivo. CD11b+ metastasis-associated macrophages are recruited by metastasing cancer cells. Their depletion reduces the number and size of metastasis, suggesting that their recruitment is essential for persistent growth of cancer cells. However, there is a need for imaging tools that report the localisation and cell fate of these macrophages to understand how they help tumour cells to progress in the TM. By means of Dynamic Combinatorial Chemistry, libraries of cyclic peptides will be generated from individual tetrapeptides through reversible disulfide bonds. Governed by thermodynamics, DCC will amplify cyclic peptides showing high affinity for CD11b+ macrophage receptors, involved in the development of metastasis. This technique will supply specific cyclic peptides targeting CD11b. Click chemistry (i.e. CuAAC) will allow the conjugation of these peptides to macrophage-specific fluorophores to generate FLUOROMACS. FLUOROMACS will enable selective imaging of CD11b+ macrophages by means of receptor-mediated endocytosis. Selectivity will be confirmed in vitro using macrophages from normal cohorts and knockouts. Finally Fluoromacs will be optimised as in vivo imaging probes for metastasis-associated macrophages. In a nutshell, MACROIMAGING will provide the first generation of chemical probes for imaging metastasis-associated macrophages in vivo. This methodology will also have enormous impact in other areas of chemical biology, such as protein recognition, drug discovery and theranostics.

Mots clés : imaging tumour microenvironment metastasis dynamic combinatorial chemistry fluorogenic probes cyclic peptides

Participants :
- University of Edinburgh (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €