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

Many animal species generate acoustic signals for social communication and are faced with the challenge to distinguish external from self-generated sounds. How does the brain accomplish this when all sounds are coming in through the ear? It requires that self- generated and external sounds are separated at some point in the central auditory system. Copies of motor commands indicate to auditory brain areas when self-generated sounds are expected to arrive. This feedforward signaling suppresses neural responses in primary auditory nuclei, as well as the auditory cortex. Neurons that are activated with self- vocalization are also found in the auditory cortex. Yet, how the signal arrives there and where along the auditory processing pathway neural encoding of self-generated and external sounds diverge, is largely unknown. These are challenging questions to address because single-cell activity needs to be recorded simultaneously across several distant brain regions. This is currently only possible with fluorescent imaging techniques, but adult vertebrate brain tissue is too opaque for large-scale optical access. Danionella translucida (DT) is a transparent, miniature fish that vocalizes in social contexts and is therefore uniquely suitable for studying whole-brain activity of auditory processing during self- vocalization. Here I propose to generate an unbiased, whole-brain map of neural activity correlated with vocal self-representation and its cancellation. For this, I will establish stimulations of fictive vocalizations in DT and combine these with auditory playback while performing whole-brain calcium imaging. This data will offer unprecedented insights into vocal-auditory interactions across a vertebrate brain.

Mots clés : auditory vocal interaction, efference copy, vocal motor control, fictive behavior, whole  brain imaging

Participants :
- Charité - Universitätsmedizin Berlin (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 162806.4 €
Projet BioCointegration (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Mathematics
Statut du projet : SIGNED

Many biological systems can be seen as networks of interconnected oscillating units. Unraveling how they interact, coordinate and influence each other in a random environment is essential for understanding systems such as the dynamic brain. The problem is that the current statistical methods are insufficient for solid data analysis. To solve this problem, I will elaborate the methodology of cointegration analysis, which has been applied mainly in econometrics, to provide a principled statistical framework for analyzing experimental data from neuronal systems. I will work on this project under the supervision of Professor Susanne Ditlevsen at the University of Copenhagen (UCPH).

Mots clés : cointegration, biological oscillators, coupling, eeg data

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet GlycoPeptides (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Many important biological processes involve binding of proteins to carbohydrates, including the recruitment of immune cells to tissues by proteins called selectins. The core binding requirement of all three types of selectins is a four sugar unit called the Sialyl LewisX epitope. However, affinity for this epitope alone is low. Further requirements for binding of selectins to their glycoprotein ligands include other carbohydrate and protein moieties, as well as sulfation of the carbohydrate or tyrosines. Open questions include what is necessary and sufficient for tight binding to each selectin, what sorts of ligands can bind to all selectins, and how the binding requirements can be presented on a synthetic scaffold. Answers to these questions will lead to a better understanding of the selectins, tools for future biological studies, and hopefully new medications for the many immune disease processes in which their abnormal functioning has been implicated. I will combine my background in peptide selection technologies with the host expertise in lectins and bio-orthogonal chemistry to bring the power of evolution-based techniques to bear on these questions. Carbohydrates and sulfotyrosines will be incorporated in a scaffold of genetically tagged macrocyclic peptides, then selection pressure will be applied to a hugely diverse library of random structures. This will provide ligands that can bind to each selectin, as well as ligands that can bind to all selectins, and subsequent comparison of these ligands will illuminate the particular requirements for interaction with each selectin, as well as revealing shared features recognized by all. In addition to an increased understanding of the selectins, through this project I will gain new expertise in the glycosciences, share my unique experience with in vitro peptide selections using genetic code reprogramming – a technique not currently used in any laboratory in Europe – and kick-start my independent research career.

Mots clés : glycoscience, carbohydrate chemistry, glycosylated peptides, lectins, in vitro evolution, mrna display, genetic code reprogramming, macrocyclic peptides, de novo peptide discovery

Participants :
- Utrecht University (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 177598.8 €
Projet SSFI (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Molecular movies depicting chemical reactions via attosecond (10^-18 s) snapshots, which vastly improve our understanding of molecular dynamics is within our grasp. Strong-field imaging techniques under development, such as photoelectron holography, promise just this. However, up until very recently all strong-field theoretical models have neglected spin and spin-orbit coupling. Initial work including spin in the initial state, along with recent experiments, has shown that spin in strong-field processes is vitally important, leading to different ionisation probabilities which in turn may alter the all important electron dynamics. In this project, I will utilise and develop cutting edge theoretical frameworks to fully include electron spin for strong-field processes in atoms and molecules. I will develop a semi-analytic model, which fully includes spin and spin-orbit coupling for single active electron and two active electron cases. This is motivated by the long history of semi-analytic methods that have been developed in this field, which have enabled unprecedented access into the electron dynamics for strong-field processes. As such, developing a model for spin will reveal deep new physical insight. I will validate the methodology by exploiting my supervisors expertise and contacts, collaborating with theorists employing complementary cutting-edge numerical models and with the only group of experimentalists to have performed spin measurements on strong-field processes. A proper treatment will allow more advanced and robust imaging techniques. I will explore the use of spin to enhance existing imaging processes such as photoelectron holography. Furthermore, I will develop the semi-analytic model for two electrons and explore spin entanglement and correlation with momentum in two-electron ionisation processes, to design entirely new imaging procedures. This analysis will also open up the possibility of exploiting this system for quantum information purposes.

Mots clés : strong field physics, spin, electron holography, non sequential double ionisation

Participants :
- Aarhus University (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet SEDiLINK (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Monitoring datasets available to evaluate past mining impacts on catchment and coastal environmental quality are severely limited in temporal extent presenting a major hindrance to effective decision making for management of legacy pollution to achieve the goals of the EU Water Framework Directive and Mining Waste Directive. The “Sediment linkage between land, river and sea: evaluating impacts of historic mining on sediment quality in the coastal zone” (SEDiLINK) research project will develop an innovative sedimentological approach to overcome these important challenges and close this substantial knowledge gap. The SEDiLINK approach will bring together established techniques (e.g. Pb-210 geochronology) with new approaches in evaluating riverine ecosystems (e.g. Pb isotope fingerprint) and deliver an integrated toolkit for evaluation of mine waste impacts. The extensive metal mining history of Tamar River Basin and coastal zone, southwest UK, offers an ideal test-bed in which to develop the novel and powerful SEDiLINK approach for wider application in other EU contaminated fluvial and coastal ecosystems requiring longer term remediation legacy pollution. Through developing this tool, the candidate will gain new scientific and technical skills in cutting edge isotopic fingerprinting techniques working with multidisciplinary and multinational groups in UK and Spain, developing and complementing her previous knowledge in radiotracer applications. This period of advanced training and mobility will underpin maturation and independence as a leading EU researcher.

Mots clés : catchment sediment dynamics, sedimentation, floodplain, salt marsh, coastal management, mining pollution, isotopic fingerprinting

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

Monoclonal Antibodies (mAbs) have gained an important place in the therapeutic arsenal of anticancer drugs. mAbs are glycoproteins containing a conserved N-linked glycosylation site at residue Asn297 of the fragment crystallisable (Fc). Most of the mAbs approved by the EMA are commercialized as a complex mixture of glycoforms at this site. It is well stablished that the precise chemical structure of the N-linked glycan modulates the effector functions mediated by the Fc domain. Specifically, for cancer treatment applications, the lack of fucose on the glycan structure contributes to enhance the effector functions of the antibodies, via increased affinity of IgG1 for FcgRIIIa on immune cells. New strategies to glycoengineering mAbs with homogenous glycoforms and lacking fucose core on their glycan structures have become a priority for the biopharmaceutical industry in order to obtain “biosuperior” anticancer drugs. Here, we will engineer a novel fucosidase enzyme that can act on fully glycosylated mAbs in order to simplify the chemoenzymatic synthesis of antibody drugs, based on the host laboratory expertise in Carbohydrate Active Enzymes. We will address three specific aims: (1) to define the structural basis of EndoS antibody specificity; (2) to elucidate the molecular mechanisms of IgG defucosylation by AlfC; and (3) to engineer an enzyme with fucosidase activity and specific for IgG. The GlycoMabs project will provide me an excellent and unique career opportunity by learning new skills in structural biology, protein engineering and project management which will grant me a leading independent position. Moreover, I will explore the industry interest in the application of our novel enzymes to generate homogeneous and afucosylated antibodies through an intersectoral secondment. Altogether, we will contribute to construct the next generation of therapeutic glycoengineered mAbs to tailor the immune reactions and increase their clinical potency.

Mots clés : carbohydrates, glycans, glycobiology, glycosyltranferases, glycoside hydrolyses, glycosylation, glycoprotein

Participants :
- CIC bioGUNE (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet deCrYPtion (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

More than 190 species belong to the Mycobacterium genus. Among those, several are pathogenic to human and animals. The high number of human lives lost and the economic consequences of livestock infection are important incentives in the control and eradication of the responsible organisms. M. tuberculosis, one of the causative agents of tuberculosis (TB), is the most problematic representative: in 2016, 1.7 million deaths worldwide have been attributed to TB. Like for other infectious organisms, antibiotic resistances have appeared in Mycobacterium. Thus, there is a fundamental need to develop new antimycobacterial drugs. The inhibition of enzymes belonging to the Cytochrome P450 (CYP) protein family has been shown to suppresses the growth of several Mycobacterium species, making CYPs targets for drug development. Unfortunately, most CYPs are considered orphan: proteins for which no physiological function is known. The deCrYPtion action aims to define the physiological function of a selected set of mycobacterial CYPs. It will prove determinant in the development of new antibiotics. I will perform a large-scale comparative genomics analysis of the CYPs encoded by Mycobacterium species, in order to define orthologous groups and identify, for each, conserved partners and pathway context. This approach is extremely powerful (even if not frequently used) and allow to propose physiological functions, based on the information obtained. Specific CYPs to be characterized will be selected based on a set of stringent considerations, including their potential as drug targets. A preliminary analysis illustrates the approach that will be used. A combination of complementary biochemical, genetics and physiological experiments will be performed to validate the hypotheses generated. deCrYPtion will be undertaken within the Centre for Cytochrome P450 Biodiversity, under the supervision of Prof Steven Kelly, at Swansea University (Wales, United Kingdom).

Mots clés : enzyme of unknown function, cytochrome p450, orphan, mycobacterium, tuberculosis, smegmatis, azole, antibiotic, drug, resistance, comparative genomics, sequence similarity network, hypotheses

Participants :
- Swansea University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet NePLeP (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

More than 600 Netherlandish seventeenth century paintings decorate the walls of Ledreborg Palace (Lejre, Denmark). The painting collection, of which a large share presumably was brought together in the first half of the eighteenth-century, consists mostly of mass-produced paintings, a novel commodity of the seventeenth century. Fascinatingly, Ledreborg Palace is not the only collection in Denmark which displays a strong emphasis on Netherlandish paintings: at least 2 other (also not disclosed) collections are known. However, the question why the Danish seem to have had a strong interest in Netherlandish paintings remains unanswered. This research will contribute to understanding the strong interest in Netherlandish paintings in Denmark during the seventeenth through eighteenth centuries by focusing on the collection of Ledreborg Palace. All the paintings will be thoroughly examined from an art historical viewpoint, however, also technical studies such as infrared and X-ray images will be carried out in order to understand also the artists working methods in their mass-production endavours to supply the entire European continent with affordable paintings. The overall result will be an improved understanding of the spread of Netherlandish art and the means by which this could be done. All the achieved data will be accessible for researchers and the public through an open-access database with 600 annotated paintings including an art historical and technical study of a carefully selected part of these hitherto undocumented and unstudied paintings. Simultaneously the latest expertise in socio economic art history will be employed to situate the paintings in a European framework of the seventeenth century and their importance to the society of today. The project will provide the young professional researcher with new and essential training to become an expert in the application both technical instruments and socio-economical study of Netherlandish paintings.

Mots clés : netherlandish art, denmark, examination of paintings, multidisciplinary research

Participants :
- National Gallery of Denmark (Danemark) — Coordinator, beneficiary, Recherche, subvention : 200194.8 €
Projet MAPSYNE (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

More than one billion people worldwide (165 million in Europe) suffer from diseases of the central nervous system (CNS). With Europe's aging societies, the European Commission identified brain research as one of the key research areas under healthcare (https://ec.europa.eu/research/health/). Many neurodegenerative diseases are still without cure (e.g., Parkinson’s, amyotrophic lateral sclerosis (ALS) and Alzheimer’s) and repeated failures in clinical trials increase the demand for novel screening technologies to be implemented in the early phases of drug discovery. Recent studies show that synaptic dysfunction is involved in CNS diseases. New technologies for neuronal screening targeting synaptic and network activity, combined with disease model cells in vitro, will enable novel functional assays for CNS drug discovery. This project aims to develop MAPSYNE, a Miniaturized Automated Patch-clamp SYstem combined with high-density microelectrode arrays (HD-MEAs) for multi-scale functional mapping of NEuronal networks. Patch-clamp allows detection of synaptic events and action potentials (APs) of single cells, while HD-MEAs record APs of thousands of neurons in parallel (also track APs propagating along axons). Combining the two methods will allow access to neuronal electrical signals across spatial and temporal scales. MAPSYNE's main objectives are (1) the development of hardware and software for a fully automated mini-patching system on HD-MEAs and (2) proof-of-concept experiments using primary and human induced pluripotent stem cell (h-iPSC)-derived neuronal networks. MAPSYNE will be designed for long-term, label-free recording of cell cultures. Other applications include local application of drugs (e.g, synaptic blockers on neuronal compartments). After this project, the ER envisions the commercialization of MAPSYNE, and eventually, its usage for preclinical CNS drug discovery.

Mots clés : patch clamp electrophysiology, multielectrode arrays technology, synaptic activity, network connectivity mapping, human induced pluripotent stem cell derived neurons, axons

Participants :
- Maxwell Technologies (Switzerland) (Suisse) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 187419.6 €
Projet OPRAS (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Mosquito-borne diseases present one of the greatest threats to human health. Mosquitoes find humans by detecting human body odour and CO2 with their olfactory system. This project addresses the fundamental and still unresolved question of how odorant valence is coded in the brain and why odorants that are attractive (positive valence) at low concentrations, switch to being repulsive (negative valence) at high concentrations. This phenomenon of valence switch is well conserved throughout the animal kingdom and represents an ideal paradigm to address a key question in the neurosciences, i.e. how information processing in neuronal networks leads to behavioural responses. To advance the understanding of valence coding and olfactory processing, the Experienced Researcher (ER) will capitalise on her detailed knowledge of the evolutionary well conserved olfactory system of the fruitfly Drosophila melanogaster, using its powerful genetic and experimental approaches (e.g. Riabinina et al, 2015, Nature Methods; Gao et al, 2015, Nature Neuroscience). The key goal of the project is to identify patterns of neuronal activity that code for odorant valence. To achieve this goal, we will record responses of small subsets of genetically labelled second-order olfactory neurons by patch-clamp while activating olfactory receptor neurons optogenetically or by odorants of known behavioural valence. We will apply statistical and machine learning techniques to detect parameters of neuronal activity, indicative of odorant valence. This project is significant for three reasons. First, it will dramatically improve our understanding of the mechanisms of olfactory processing likely applicable across species. Second, it will create new genetic reagents and experimental solutions, widely applicable across research areas and model organisms. Third, it will create a solid foundation for future development of powerful olfactory control strategies of insect disease vectors.

Mots clés : olfaction, drosophila, odour valence

Participants :
- University of Manchester (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet UnequaLives (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : SIGNED

Most countries experienced major increases in life expectancy in the second half of the 20th century. This progress has meant that people are living longer on average and, at the same time, ages at death have become compressed to a narrow band of ages within populations. In other words, ages at death have become more similar, or lifespan inequality has decreased as populations live longer. The research I propose is driven by three major objectives: 1) Pioneer a powerful, theory-based methodology to analyze how age-specific patterns of mortality drive changes in life expectancy and lifespan inequality (variation in age at death), 2) Apply these methods to analyze recent patterns of life expectancy and lifespan inequality in low mortality countries, including Europe, and 3) Expand terms of discourse about the effects of violence on population health by analyzing a neglected perspective, namely lifespan inequality in contexts of high violence by sex. The data used in this project come from open-access databases, including the Human Mortality Database, the Global Burden of Disease, and the Global Peace Index. This project is timely because recent trends in several countries indicate that continued improvements in longevity are not inevitable, with stalls in life expectancy occurring in some low mortality countries, such as the UK and USA, and increasing premature mortality resulting from violence in contexts such as Latin America and Middle East. These recent dynamics indicate increasing complexity underpinning population health improvements and highlight the need to analyze population health through the lens of lifespan inequality. This has significant implications for policy, as it reveals emerging forms of inequalities that highlight the importance of adopting inequality-based metrics for evaluating population health around the globe.

Mots clés : population health, life expectancy, lifespan variation, lifespan inequality, mortality, demography, decomposition, mathematical demography

Participants :
- University of Oxford (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 224933.76 €