Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet MRCKa in cancer (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Metastasis is the primary reason for cancer death, and metastatic spread drastically worsens the prognosis of cancer patients. As cell migration is the biological process underlying the spread of cancer cells, better understanding of it is crucial for the development of novel therapies in reducing cancer invasion and increasing patient survival. Yet, little has been accomplished in terms of the development of anti-metastasis drugs. MRCKa is an effector of Rho GTPase, and molecular studies have suggested it to play important roles in cancer cell migration. However, the potential of targeting MRCKa in metastasis has not been validated due to the lack of in vivo evidence and specific inhibitors. Hence, this project aims to validate MRCKa as an important drug target for the treatment of metastatic cancers. The first objective aims to investigate the role of MRCKa in cancer development and metastasis by utilizing a breast cancer model on MRCKa knockout mice. Secondly, MRCKa was reported to influence cell migration by multiple mechanisms, including promoting cell contraction, reducing actin turnover, and filopodia formation. To better define the molecular signaling of MRCKa during metastasis, the importance of these effector pathways in cancer cell migration will be investigated. Specifically, MRCKa knockout breast cancer cell line derivatives will first be generated, and their ability to migrate and invade studied in 3D spheroid cultures. The importance of the effector pathways will be investigated through targeted gene inactivation and inhibitors. Finally, MRCKa has two closely related family members, MRCKb and MRCKg, and also shares functional similarities with ROCK1 and ROCK2. With the aim to obtain a more efficient inhibition of cancer cell migration, the third objective seeks to investigate the overlapping functions of related kinases through combining knockouts of MRCKa in breast cancer cells with knockouts of MRCKb, MRCKg, ROCK1 and ROCK2.

Mots clés : metastasis, rho gtpase, in vivo modeling, cell migration

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet PB_dormancy (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Metastatic disease is the leading cause of cancer deaths, yet our understanding of this process and therapeutic choices are extremely limited. The recent explosive development of high-throughput technologies in genomics and proteomics has begun to unravel the complexity of cancer biology, highlighting the need to approach the study of cancer from a systems biology perspective. Results of recent studies have underscored the crucial roles of the tumor microenvironment as well as cell-intrinsic processes, such as autophagy, in cancer cell survival and dissemination. These surviving cells may lay dormant or be triggered to proliferate and establish active metastatic lesions after a variable period of time. I propose an innovative project in which I will exploit the unique opportunity to dissect molecular mechanisms controlling breast cancer dormancy and metastasis employing cutting-edge technologies in the field of functional genomics. This technology includes several state-of-the-art technical advances in the fields of in vitro and in vivo modeling of tumor cell dormancy, functional forward genomics using the PiggyBac transposon-based system for insertional mutagenesis screens, next generation sequencing, advanced bioinformatics and in vitro and in vivo functional validation studies. This project will identify critical molecular processes involved in breast cancer progression and potential therapeutic targets against breast cancers at high risk for recurrence and poor prognosis. Thus, it is expected that this project will provide future translational research avenues, enhance my position to be at the forefront of cancer research and provide the opportunity to establish myself as an independent researcher following the completion of this fellowship.

Mots clés : tumor cell dormancy, breast cancer, metastasis, insertional mutagenesis, piggybac, forward functional genomics, tumor modelling, in vivo cell imaging, genetic engineered mouse models

Participants :
- Regional Government of Andalusia (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet BEAUTIPHUL MIND (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Methodological developments have equipped scientists with unprecedented opportunities to characterize brain structure and functional organization and relate it to behaviour. Yet to date, no clinically relevant tools, grounded in this neurobiology, have been developed that inform clinical outcomes in psychiatric disorders. Specifically, in autism – one of the most common neurodevelopmental conditions – there is still little knowledge about the neurobiological underpinnings of different clinical outcomes with regard to core symptoms and adaptive daily living skills. While some individuals worsen, others do better over time. Like in many realms of medicine where biomarkers have revolutionized treatment, there is also an urgent need to develop such neurobiologically-grounded predictors for clinical outcomes in autism. To date, the majority of studies have analysed small, cross-sectional samples across single neuroimaging modalities with case-control comparisons to find mean group effects. However, this standard approach ignores the large sample variation in autism. The overarching objective of my MSCA Fellowship is to establish a multimodal, longitudinal characterization of the individual neurobiological signatures that are predictive of clinical outcomes in autism. I will integrate both structural and functional neuroimaging modalities for a fine-grained characterization of the neural phenotypes in autism. Using normative modelling, I will characterize at the level of the individual (rather than with group averages) how each individual with autism is different from the neurotypical pattern of such a multimodal brain characterization and how it relates to behaviour, genetic risk and clinical outcome. This novel approach has the potential to transform clinical management in autism, leading to the development of neuroscientifically-informed, targeted interventions. I will also provide the research community with novel tools that pave the way for precision medicine.

Mots clés : autism spectrum disorder, neuroimaging, structural and functional magnetic resonance imaging, normative modelling

Participants :
- University of Zurich (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191149.44 €
Projet MOSTAPDE (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Micro/nano-electromechanical system (M/NEMS) resonant mass sensors have attracted utmost interest over the past two decades. This is due to their wide range of applications, especially in biochemistry, for instance weighing single molecules, nanoparticles, and even monitoring the growth of living cells. However, their performance is significantly decreased when operated at ambient air and measurements take a considerable time. Therefore, there are two main challenges for MEMS resonant mass sensors: (i) the improvement of the quality factor at ambient atmospheric pressure; (ii) the realization of real-time monitoring with a closed-loop control and interface circuit system. Additionally, higher sensitivity is always a desirable property to further increase the performance of mass sensors. In this project, entitled “MOde-localized mass Sensors with Thermal Actuation and Piezoresistive DEtection (MOSTAPDE)”, I aim addressing aforementioned challenges by combing thermal actuation and piezoresistive detection for MEMS resonators. With this approach a quality factor of several thousand at ambient pressure can be achieved. As a further novel approach, it is proposed to weakly couple two resonators and exploit the phenomenon of mode localization; by using the amplitude ratio as readout metric compared to the commonly used frequency modulation method; in this way the sensitivity can be enhanced by 2-3 orders of magnitude. Furthermore, the inherent common mode rejection property of mode-localized sensors can be exploited for higher robustness. Finally, particle contamination and blockage are avoided as the proposed sensors do not require small electrode-gaps as conventional capacitive sensors. For the microfabricated sensors, a closed-loop control circuit will be constructed to enable real time monitoring. We plan to demonstrate the concepts for measuring particulate matter, which is a major air pollutant, as a practical application of mass sensing.

Mots clés : mass sensor, mode localization, thermal actuation, piezoresistive detection, quality factor, sensitivity, closed loop circuit

Participants :
- KU Leuven (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 178320.0 €
Projet Cryoetch (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Microchips have caused a revolution in electronics over the last few decades. Following Moore's law, much effort has been put into continuously shrinking electronic feature dimensions. Indeed, typical feature sizes of semi-conductor decreased from 10 µm in 1971 to 14 nm in 2014. With the shrinkage of feature sizes, plasma etching plays a more and more important role due to its anisotropy during surface processing. However, to go beyond 14 nm features, current state-of-the-art plasma processing faces significant challenges, such as plasma induced damage. Recently, one such novel process with limited plasma damage is cryogenic etching of low-k material with SF6/O2/SiF4 and CxFy plasmas. In this project, the fundamental mechanisms of the plasma, and its interaction with the surface, for these gas mixtures, will be studied to improve cryogenic plasma etching. For this purpose, numerical models (a hybrid Monte Carlo - fluid model and molecular dynamics model) will be employed to describe (i) the plasma behavior for SF6/O2/SiF4 and CxFy gas mixtures applied for cryogenic etching, and (ii) the surface interactions of the plasma species with the substrate during etching. Furthermore, cryogenic etch experiments will also be conducted to validate the modeling results during the secondment. Such an interdisciplinary project, including chemistry, physics, mathematics, computer modeling and chemical engineering, will definitely widen the applicant’s expertise in different plasma investigation approaches.

Mots clés : plasma etching, plasma chemistry, plasma physics, plasma surface interactions, computer, modelling

Participants :
- University of Antwerp (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160800.0 €
Projet POSEIDOMM (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Microplastics represent an increasing threat to aquatic ecosystems, with potential impacts on the cycling of fundamental elements and ecological consequences at all trophic levels. Low-density polyolefins, like polyethylene and polypropylene, are the most common plastics produced and are ubiquitous in marine environments. Floating on the sea-surface, they can have direct and indirect impacts on the sea-surface microlayer (SML), a key interface for biochemical and photochemical processes controlling gas exchange between the ocean and the atmosphere. The SML is an enriched biofilm of organic biological material aggregating and favouring high microbial activity. The effects of an increasing presence of microplastics on the cycling of organic matter in the surface ocean are not well understood, and yet they may have a major impact on this key interface. POSEIDOMM will investigate the influence of microplastics on the photochemical and biological processes in the SML. We will verify the effect of microplastic pollutants on the formation of a surface-active biofilm, the implications for microbial cycles and for the photochemical generation of reactive chemical species and labile organic compounds. The goals of POSEIDOMM are to provide a chemical and biological characterization of the microplastic-biofilm aggregates in the SML, to quantify the photochemical cycling of such aggregates and to identify the implications of this cycling on gas exchange and on the microbial carbon cycle. This will be achieved through a trans-disciplinary approach combining innovative spectroscopic and biological analyses to study the SML in controlled microcosms and in-situ mesocosm studies. Through a close cooperation with leading European partners, POSEIDOMM will close major gaps in our understanding of the interaction of micropollutants with marine biological processes and atmospheric gas exchange.

Mots clés : microplastic pollution, sea surface microlayer, dissolved organic matter, marine gels, microbial loop, photochemistry, air sea gas exchange

Participants :
- University of Siena (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 180277.2 €
Projet ZeoSynMech (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Microporous materials are crystalline, framework structures that contain pores of less than 2 nm. They commonly exhibit robust hydrothermal stability and are used in a wide range of areas including catalysis, separations, ion exchange and adsorption where their shape and size selectivity often shows superior performance over other materials. They are formed by crystallization from amorphous inorganic oxides, but the underlying mechanisms that govern the crystallization of microporous materials are poorly understood, despite extensive work in this area. This lack of understanding means that the development of new materials and compositions is an inefficient trial and error process mainly guided by heuristics. In this work I propose to study the formation principles of microporous materials through 3D spatiotemporal element mapping and monitoring the incorporation of spectroscopically active and catalytically interesting heteroatoms, namely copper and titanium, in distinct framework structures. This proposal uses two distinct approaches (ex-situ STXM and in-situ spectroscopy) to study two different inorganic chemistries (aluminophosphate and silicate) with two different spectroscopically active heteroatoms (copper and titanium) and four different microporous material frameworks (AFI, CHA, MFI and MWW) in order to probe the underlying crystallization mechanisms behind microporous material synthesis and crystallization. The unprecedented combination of 3D spatiotemporal element mapping at various stages of crystallization combined with in-situ spectroscopic studies of catalytically active elements will lead to previously unavailable information about the underlying mechanisms governing the formation of these materials. These insights will lead to innovations in synthesizing both known and novel materials and compositions.

Mots clés : microporous materials, zeolites, crystallization mechanisms, in situ spectroscopy, spatiotemporal characterization

Participants :
- Utrecht University (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165598.8 €
Projet MsInfection (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Microsporidia are emerging pathogens of high priority that infect humans, and most animals. Microsporidiosis can be life-threatening and cause severe damage in the eyes, brain, muscles, respiratory, and urinary tracts. These obligate intracellular parasites also present a unique case of reductive and divergent evolution. They possess the smallest eukaryotic genome and unique cellular features such as the smallest eukaryotic cytoplasmic ribosomes and a specialised infection apparatus, the polar tube. Inside the host, microsporidia replicate through distinct life stages to form infective spores that are released into the environment upon host cell lysis. However, the molecular events involved in the pathogen’s commitment to each life stage, host cell lysis, formation, and eversion of the polar tube, remain unclear. This lacunae in understanding microsporidia are due to a lack of biochemical or structural data and the absence of systematic in vivo studies. Thus, studying this medically and economically relevant pathogen is critical for designing drugs and preventive regimes to curtail their transmission. Towards this, MsInfection aims to provide the first comprehensive and mechanistic insights into microsporidian life-cycle progression and host cell invasion. The life cycle stages of microsporidia species with varied tissue tropism will be analysed structurally and transcriptomically at the single-cell level, using Electron Microscopy (EM) and single cell-RNA sequencing (scRNA-seq). A combination of these transformative technologies will enable a systematic determination and visualisation of the molecular events driving intracellular development, and the assembly of infection apparatus and tissue niche selection.

Mots clés : microsporidia, cryo sbf, cryo electron tomography, single cell transcriptomics, electron microscopy, polar tube

Participants :
- Umeå University (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 191852.16 €
Projet MicroMISTRANS (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Microsporidia are ubiquitous and poorly treatable eukaryotic obligate intracellular pathogens that threaten human health and industrMicrosporidia are poorly treatable eukaryotic pathogens that threaten human health and industrially valuable insects, fish, and cattle. Despite Microsporidia being recognized as emerging pathogens that require development of new drugs, many aspects of their biology remain totally unexplored due to a lack of appropriate genetic tools and because only a handful of laboratories in the world can grow and manipulate Microsporidia in infected host organisms or cell cultures. This proposal involves a promising scientist with a background in biochemistry and molecular biology and who will move to a host laboratory in Newcastle University, UK – a renowned center for excellent training of young researchers, and a leading research center in the field of pathogen evolution. The researcher will undertake a multidisciplinary investigation, combining microbiology, proteomics, and molecular biology, in order to investigate how Microsporidia diversify their proteomes through error-prone protein synthesis (mistranslation). The researcher’s training at the host laboratory – in cultivating and manipulating Microsporidia in mammalian cell lines for proteomic and toxicity studies – will synergistically complement the researcher’s expertise in molecular biology of protein synthesis. Completing the project will equip the researcher with a rare, increasingly valuable and transferable skill of Microsporidia experimental biology that will be a key asset in his transition to an independent research career. The project will deliver the first detailed insights into the ability of Microsporidia to produce myriad protein isoforms from their genes as a result of highly inaccurate translation. The outcome of this project will have general implications for understanding how eukaryotic pathogens can modulate their interactions with the host and evade host immune systems.

Mots clés : microsporidia, fungal pathogens, intracellular parasites, genetic code mistranslation

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

Migration by nationals of sub-Saharan countries to the Sahara, often assimilated by African and European public institutions to departures to Europe, have, over the last decade, become the object of increased surveillance. The European Union has put migration at the heart of its relations with Africa, and finances a broad range of programmes that aim at a better management of migration in the Sahara. Ranging from encouragement of legal reforms to assistance in the repatriation of migrants, via equipping border posts with sophisticated means of control, EU interventions in the area take different forms, but they all have in common that little is known of their actual impact and side-effects on the ground. The aim of this research project is to study the nature and practical results of European intervention in migration issues in the central Sahara, and its global cost, by combining an exhaustive analysis of European policies with empirical fieldwork, with a view towards understanding and correcting the representations and assumptions that underpin them. The project will be hosted by the International Migration Institute (IMI) at the University of Oxford. The IMI is a leading research centre with regards to international migration and the legality and legitimacy of international intervention. Training at and collaboration with the IMI would allow the researcher to develop an innovative theoretical framework for future research, leading to a critical turn in his career. Results of the research will be of considerable academic and public interest. Most importantly, it will have important implications for European migration policy, producing reports that should become required reading for everybody involved in these matters. The candidate will do his utmost, during and after the fellowship, to reach this potential institutional audience.

Mots clés : migration, policies, development, state, border management, sahara, niger, chad

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