Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet MemTrain (Horizon 2020, appel à projets 2018)
Action : Cofund Doctoral programme
Statut du projet : SIGNED

All organisms, from bacteria to humans are made of cells surrounded by membranes, which define them, separating them from their environment. Membranes precisely control what enters and leaves cells and how cells interact with each other and molecules in their environment. All these processes are fundamental to life; by harnessing and understanding them, we have the potential to influence human and animal health and disease, and generate improved microorganisms for biotechnological applications in the food, chemical and drug sectors. The membrane has traditionally proven relatively intractable to study, mainly due to its hydrophobic nature. However, recent technological and methodological advances, with key inputs by Aston University, have enabled this field to progress rapidly. There is now an urgent need for increased research training in this area. There is established and emerging evidence for the involvement of the membrane in a wide variety of industrially-relevant processes, encompassed by MemTrain’s three core themes of medicines discovery, biotechnology and underpinning technology development. MemTrain is a five-year multidisciplinary, intersectoral PhD training programme for 12 PhD researchers. This programme will train the next generation of researchers who are primed to work on developing a new understanding of how to harness the full potential of cell membranes by working the interface of industrial and academic science. To work across these traditional boundaries, researchers will require a diverse skillset enabling them not only to undertake fundamental research but to apply this knowledge to current real-world problems underpinned by excellent communication and transferable skills. Innovative, collaborative training programmes within MemTrain will equip these research leaders with these vital skills, allowing them to drive the future of intersectoral research across Europe and the world.

Mots clés : membrane

Participants :
- Aston University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 976320.0 €
Projet DReM-PCM (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

All-dielectric optical metasurfaces have recently attained much attention due to their ability to provide higher efficiencies than the more conventional plasmonic metasurfaces, and for their ability to readily work in both reflection and transmission. However, the functionality of traditional dielectric-based metasurfaces is fixed-by-design, i.e. the optical response is fixed by the size, arrangement and index of the nanoresonators. A far wider range of applications in many important technological/industrial fields, ranging from communications, to sensing, robotics, displays and much more, could be addressed if active/reconfigurable control were possible. One promising all-dielectric reconfigurable metasurface approach arises from the combination of high-index dielectric nanostructure arrays with chalcogenide phase-change materials (e.g. GeSbTe alloys). The latter can be electrically, optically or thermally switched between their crystalline and amorphous states, or to intermediate states between the two, with ultra-low energy consumption in a non-volatile manner and exhibit remarkably different optical properties between phases. It is therefore possible to achieve an all-dielectric reconfigurable metasurface by continuously tuning the phase states of the chalcogenide alloy. However, very few dielectric metasurface designs incorporating phase-change materials have been explored to date, and those that have been reported are switched through ex-situ means, while some form of in-situ switching is definitely required to meet real device applications. To achieve this objective, we will (1) theoretically design and experimentally fabricate two reconfigurable all-dielectric phase-change metasurfaces whose in-situ switching is electrically realised by an integrated microheater and by a crossbar structure respectively, and (2) continuously tune the optical response of the designed metasurfaces for potential optical applications such as Lidar type beam steering).

Mots clés : metasurface, in situ switching, phase change materials

Participants :
- University of Exeter (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €
Projet Co-coAssembly (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Almost all fundamental biological processes involve protein complexes and therefore, efficient folding and assembly of homo- and hetero-oligomers is critical for cellular functionality and integrity. Recent studies have shown that many protein complexes assemble co-translationally by one fully-synthesized subunit engaging another subunit that is still in nascent state (co-post assembly). An ongoing study in the Bukau lab now revealed that assembly can also occur by interaction of two partner nascent chains (co-co assembly). Co-co assembly is mostly employed for the formation of homo-oligomers and exists in all kingdoms of life.. Despite initial evidence of its existence, very little is known about the molecular mechanisms driving co-co assembly. This includes information on whether co-co assembly requires co-localization of two polysomes or can happen on one polysome.. Furthermore, it is currently unclear whether co-co interactions require preceding nascent chain folding steps and to what extent co-translationally acting chaperones coordinate the process and the impact of translation speed on co-co assembly. I propose to study mechanisms of co-co assembly using the dimeric chorismate mutase (PheA) as a representative top candidate from a high throughput screen for co-co assembling protein complexes in E. coli. Employing cryo-electron tomography, I will analyse the three dimensional arrangement of E. coli ribosomes in the context of a polysome to assess how organization of translational machinery allows co-co assembly. Moreover, I will study the co-translational cascade of folding steps of chorismate mutase by utilizing FRET on in vitro prepared nascent chains. Finally, I plan to explore the impact of co-translationally acting chaperones and translation kinetics on co-co assembly, by performing disome-selective profiling analysis in chaperone mutant cells lacking Trigger Factor and DnaK and in mutants that synthesize proteins with reduced translation kinetics.


Participants :
- Heidelberg University (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 174806.4 €
Projet NewLoops (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Almost all we know about particle physics and the Standard Model comes from scattering experiments and our ability to predict them via scattering amplitudes (these measure probabilities of scattering processes). To meet the impressive technological advances of particle colliders like the Large Hadron Collider at CERN, new tools and concepts have emerged over the last 25 years. More than giving methods, they have triggered a revolution in our understanding of the formal microscopic structure of particle physics, a subject people thought they knew everything about. My program is based on a set of formulæ due to Cachazo, He & Yuan (CHY), that challenge the way we think about scattering amplitudes. They relate to 'twistor' ideas and string theory. The former aims at manifesting the geometry of field theories, but failed so far to grasp their quantum-ness. The latter, in spite of its mathematical beauty, has the drawback of having additional contributions that are hard to decouple from the field theory ones. The CHY formulæ retain the advantages of both methods, and lead to a variety of remarkable expressions for scattering amplitudes in a increasing number of theories, including gauge, gravity and scalar theories. In a crucial work, I showed that these methods actually carry over to the first quantum correction: this was the first time ever that twistor methods were shown to work at the quantum level. My project aims to extend this and reformulate the full pertubative quantum expansion of field theories in the CHY language. This would be a major conceptual advance. I explain that to do so will require to understand a more fundamental object called Null String, whose quantization will shed light on my 'quantum CHY formalism'. I also propose applications of the formalism of interest for LHC physic, like a third order calculation for the 2 to 3 gluon scattering in gauge theory, that all other existing methods have failed to determine so far.

Mots clés : high energy physics, scattering amplitudes, string theory, gauge theories and gravity, precision calculations

Participants :
- European Organization for Nuclear Research (Suisse) — Coordinator, beneficiary, Recherche, subvention : 175419.6 €
Projet SYN-CHARGE (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Alpha-synuclein (aSN) is an intrinsically disordered protein (IDP) expressed by neurons, and well-known to aggregate in so-called Lewy bodies (LB) that are a hallmark of Parkinson’s disease (PD) and other LB disorders. Despite extensive research, the mechanisms underlying its toxicity in these disorders still remains to be understood. In this project, I will determine whether aSN can interact with other disordered proteins in a novel, mean-field type interaction, focusing on the disordered loop of the neuronal plasma membrane Ca2+ ATPase (PMCA). I will study this using biophysical techniques, in particular NMR, ITC and SAXS/SANS. This project will improve the understanding of aSN and its interactions and has the potential to pave the way for new discoveries, especially in drug design. I will gain important experience in project design and management, a research network in Europe, and take a significant step towards independence. I will undertake this project at the University of Copenhagen in the research group of Professor Birthe B. Kragelund, an expert in the field of IDP research. The Kragelund group has recently joined the BRAINSTRUC Consortium: a group of researchers working on the structural characterization of neuronal proteins. Thus, they required a postdoctoral researcher with a strong background in neuroscience and structural biology. I was uniquely qualified to take this position as I have been working on neurodegenerative proteins for several years and structurally characterized the IDP associated with Huntington’s disease. Professor Kragelund has experience supervising productive postdoctoral researchers, an extensive European network, and has access to the state-of-the-art facilities necessary to complete this project. I have recently acquired preliminary data to indicate that the two proteins (aSN and PMCA) interact directly. This project has the potential to change how we understand proteins associated with neurodegeneration and their interactions.

Mots clés : intrinsically disordered proteins, idps

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 219312.0 €
Projet SOCIALBRAINCIRCUITS (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Also known as velocardiofacial or DiGeorge syndrome, 22q11.2 deletion syndrome (22q11.2DS) is currently considered as the highest genetic-based vulnerability factor for neuropsychiatric disorders, such as autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorders and schizophrenia. Noteworthy, this microdeletion leads to a wide range of peripheral and central symptoms, including severe deficits in face memory and social cognition, which remain incurable to date. Thus, the present proposal aims at delineating the neuroanatomical substrates of social behavior in order to identify new therapeutic avenues for social deficit in velocardiofacial syndrome and its associated neuropsychiatric disorders. To this purpose, we will use a very solid murine model of 22q11.2DS, the LgDel+/- mouse, which similarly displays deficits in social interaction, to investigate the respective interventions of the oxytocin (OT) and the dopamine (DA) system in the implementation of normal versus altered social behavior, at critical time periods (first post-natal days and adolescence). Specifically, preliminary findings from the host laboratory suggest that early alterations of the OT system, by preventing proper GABA switch in the medial prefrontal cortex (mPFC), leads to abnormal mPFC regulation of DA function in the nucleus accumbens and/or amygdala, and subsequent social deficits at adulthood in LgDel+/- mice. We will address this hypothesis by using a multidisciplinary strategy encompassing genetics, molecular biology, biochemistry, tracing methods, cell culture, as well as viral and behavioral approaches. The originality of the present project, which resides in our will to identify the developmental trajectories of social behavior, together with a reciprocal transfer of theoretical, practical and transferrable skills between the host laboratory and me, will allow me to develop independent research projects and a competitive research career.

Mots clés : 22q11 deletion syndrome, social behavior, prefrontal cortex, nucleus accumbens, amygdala, oxytocin, dopamine, gaba, glutamate

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 168277.2 €
Projet CircaDopamine (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Alterations in sleep/wakefulness behavior are among the most debilitating and highly prevalent non-motor symptoms of many neurological and psychiatric disorders that originate from perturbations of the Dopamine (DA) system. Currently, no effective therapeutic strategies are available to alleviate these symptoms. Inspired by my Ph.D results, the current proposal aims to investigate in detail the role of dopamine in the regulation of sleep and circadian rhythms. The main question under investigation is; By what mechanisms DA regulates sleep and circadian rhythms and how are these affected in diseases (such as Parkinson)? Two transgenic mouse models will be used; the first model (MitoPark) shows, like in Parkinson’s disease (PD) patients, a progressive age-dependent neurodegeneration of DA neurons. The second model (CircaDA) lacks functional clock gene oscillations selectively in DA neurons. Using polysomnography in MitoPark mice, a detailed investigation of the consequences of DA loss on sleep regulation will be performed. In-vivo multiunit electrophysiology will be used in both mouse models to study the role of the circadian changes in DA neurotransmission in driving and/or synchronizing the electrophysiological properties of striatal and cortical neurons. Finally, selective DA receptor drugs will be combined with in-vitro patch clamp electrophysiology and in-vitro Per2-bioluminescence to investigate the molecular pathways used by DA to modulate multiple electrophysiological correlates of clock gene oscillations. Collectively, this proposal holds promising fundamental and translational insights for sleep problems experienced by patients suffering from DA-related disorders and is expected to significantly contribute in fostering the academic career of the researcher and the competences of the hosting laboratory in Neurodegenerative diseases.

Mots clés : dopamine, circadian rhythms, sleep regulation

Participants :
- Leiden University Medical Center (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 177598.8 €
Projet BIOMA (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : SIGNED

Alterations of the gut microbiota are implicated as a contributory factor in obesity-related metabolic dysregulation. Bacteriocins are antimicrobial peptides produced by bacteria of many genera, including several probiotic strains. These peptides are often very specific and can kill target species without causing collateral damage to host bacterial populations. Since bacteriocins are gaining credibility as precise modulators of the human microbiome, bacteriocin-producer strains are an interesting strategy to address obesity prevention and/or treatment. However, rigorous experimental methods are required to assess this. The aim of BIOMA is to study the impact of a set of different bacteriocin-producing strains with probiotic traits, on the composition of the gut microbiota and on metabolic abnormalities in obesity, through the use of wild type strains and derived mutants that no longer produce the bacteriocins. The proposal involves two complementary approaches: 1) In vitro fermentation systems that simulates the anaerobic and dynamic environment of the distal colon will be used to assess the effect of bacteriocins production on taxonomic profiles and diversity of gut microbial populations. 2) In vivo male and female murine models will be used to study changes in microbiota and whether these changes are associated with a reduction in body weight gain and an improvement in inflammatory and metabolic profiles. A secondment at Artugen (interface of academia and industry) will be a first step to face the challenging incorporation of bacteriocin-producing probiotics into foods and pharmabiotics. From a clinical perspective, the under-utilization of bacteriocins can be ascribed to a lack of awareness of what they can achieve. The outcome of BIOMA will impact clinical practice in the foreseeable future, providing an overview of the potential of bacteriocins as microbiota modulators and as a possible strategy in the prevention/management of obesity and metabolic disorders.

Mots clés : bacteriocins, microbiome, gut microbiota, lactic acid bacteria, obesity, microbial diversity

Participants :
- National University of Ireland (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 184590.72 €
Projet SPLICANCER (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Alternative splicing (AS), by affecting nearly 90 percent of human genes, is the major contributor to protein diversity. Mutations that disrupt AS regulatory sequences are a widespread source of human diseases. Various evidences suggest that an AS reprogramming is critical in cell adaptation during cancer development. In spite of increasing interest in the potential oncogenic role of AS, little is known about the molecular mechanisms behind its deregulation during the somatic to the cancer cell transformation. Our aim is to contribute to the characterisation of AS reprogramming during the somatic to the proliferative cancer cell transformation using myosin VI as model system. Recent studies from the host lab reported how myosin VI AS modulates its interactome leading to different cellular functions (endocytosis for the long isoform and cell migration for the short one). The lab found that alternative myosin VI splicing is aberrantly regulated in cancer, where exon skipping dictates cell addiction to myosin VIshort for tumour cell migration.In this proposal, we intends to 1) Identify the myosin VI’s alternative splicing regulators and define their role in vitro, 2) identify common splicing-regulated events that occur during the establishment of a fully polarized epithelial architecture and that are possibly deregulated in cancer (AS reprogramming), 3) assess whether cancer stem cells express a specific set of the identified AS genes.Preliminary results revealed that myosin VI isoforms expression can be switch on/off in selective culture conditions. We will take advantage of this beahviour to set up our analysis based on a multidisciplinary approach that includes biochemical, mass spectrometry and cellular biological assayes. The new set of information will gained with this proposal will be instrumental to understanding the molecular mechanism at the basis of AS (de)regulation for myosin VI and more in general for cell transformation during cancer progression.

Mots clés : alternative splicing, rna binding proteins, cell migration, cell polarization, oncogenic mechanisms

Participants :
- FIRC Institute of Molecular Oncology (Italie) — Coordinator, beneficiary, Recherche, subvention : 168277.2 €
Projet REVEAL (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Although East Antarctica is regarded as a keystone in the Rodinia and Gondwana supercontinents and is a pivotal component of the global climatic system it remains the least known continent on Earth. With REVEAL we aim to unveil the crustal structure, tectonic architecture and evolution of several major frontier regions in East Antarctica. The project will also address large-scale geological controls on bedrock topography, subglacial hydrology and ice sheet dynamics. Our models and interpretations of potential field data will enable us test several hypotheses regarding the effects of collision, accretion and rifting on East Antarctica. This has significant implications for comprehending the impact of supercontinental assembly and break up on the structure and evolution of East Antarctica. Using state of the art three dimensional modelling, we will obtain an enhanced understanding of intraplate mountain building in the enigmatic Gamburtsev Subglacial Mountains region. This is highly significant, as these mountains were critical for East Antarctic Ice Sheet development. The enhanced knowledge of subglacial geology that will derive from our analyses of the Recovery Frontier and Wilkes Land will facilitate new assessments of the influence of geological boundary conditions on the dynamics and the stability of these potentially more vulnerable marine-based parts of the East Antarctic Ice Sheet. The REVEAL project has a strong international dimension and will deliver several high-profile publications and dissemination activities. It will provide unique and timely training and career development opportunities for the experienced researcher.

Mots clés : east antarctica, magnetic and gravity anomalies, imaging and modelling, collision and rifting, mountain building, supercontinental assembly and break up, ice sheet dynamics

Participants :
- UK Research and Innovation (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 183454.8 €