Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet Nano-axo-syn (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neurons in the brain have extensive dendritic arbours that receive thousands of synaptic inputs all along it. The transformation of all these inputs to an output in a single neuron occurs through the integration of synaptic events and the generation of an action potential (AP) at the axon initial segment (AIS). The AIS, therefore, is the site that controls neuronal output by gating the generation of APs. It has been recently shown that this neuronal compartment can be reorganized following a change in neuronal activity and that this structural plasticity is associated with a change in neuronal excitability. In addition, the AIS of pyramidal neurons is innervated by a specific type of inhibitory interneuron, a Chandelier cell, that forms axo-axonic connections specifically with it. Therefore, the AIS can be seen as a short stretch of axon that brings together molecules critical for AP initiation (e.g. - voltage-gated channels) and synaptic proteins essential for the local modulation of excitability. The interplay between these two compartments at the nanoscale level is not known. At classical excitatory and inhibitory synapses, the nanoscale molecular organisation of synaptic proteins has been shown to be a key factor in modulating the efficiency of synaptic transmission between neurons. However, the precise molecular organisation of axo-axonic synapses is still poorly understood, as is its role in regulating neuronal output. We propose to decipher this organisation in mouse brain slices using the state-of-the-art super-resolution microscopy combined with electrophysiology. Once the nanoscopic arrangement elucidated, we will study how it is modified during activity-dependent forms of plasticity and how this, in turn, leads to changes in neuronal excitability. Finally, we will establish how this neuronal output hub is organized in a mouse model of schizophrenia in which synaptic transmission between pyramidal neurons and Chandelier cells is altered.

Mots clés : chandelier cells, axo axonic synapses, axon initial segment, neuronal output, molecular organisation, super resolution microscopy, schizophrenia

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet Schizophrenia Organoids (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neuropsychiatric disorders account for 1/5 of the total disease burden in Europe causing mental anguish and decreased quality of life for those affected, especially for schizophrenia patients. An intriguing theory suggests that altered brain development results in schizophrenia, and the selective cellular defects in parvalbumin (PV) inhibitory interneurons observed in schizophrenic patient brains. However, the role of altered interneuron development in producing these pathophysiological hallmarks of schizophrenia is currently unknown due to a lack of cellular models of human interneuron development. Cerebral organoids are a revolutionary in vitro model of embryonic brain development generating complex brain circuits and recapitulating many aspects of interneuron development. The generation of organoid tissue from hiPSCs allows for the growth of patient-specific brain tissue. Therefore, the current proposal will develop a cerebral organoid schizophrenia model to analyze PV-interneuron development. First, cerebral organoids will be grown from patient-derived hiPSCs genetically modified to include a PV-GFP reporter. Using this reporter, genome-wide PV-specific gene expression will be analyzed to identify deregulated developmental pathways during PV-interneuron development. Second, a phenotypic analysis of PV-interneuron development will determine how PV-interneuron synaptic morphology and/or migration are altered in this cerebral organoid schizophrenia model. These assays are relevant to disease-related pathology, and will include axonal morphological analysis and a novel organoid co-culture migration assay. These results will determine the role of interneuron development in the pathophysiology of neuropsychiatric disease for the first time in human tissue. Understanding the developmental mechanisms of schizophrenia will address a major unmet therapeutic need by inspiring new avenues of innovative therapeutic strategies.

Mots clés : cerebral organoids, schizophrenia, interneuron development, parvalbumin interneurons, cortical development

Participants :
- Austrian Academy of Sciences (Autriche) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 178156.8 €
Projet LightForNuLAND (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Neutrino Physics is one of the areas of Particle Physics with the highest potential for discoveries. DUNE, a long-baseline neutrino-oscillation experiment, will study the neutrino mass ordering and the charge-parity violation in the next decade using liquid argon time projection chamber (LArTPC) detectors. Until DUNE begins, the only opportunity to study actual neutrino interactions in LArTPCs is the Short-Baseline Neutrino (SBN) Program at Fermilab. SBND, the near detector of the SBN Program, will collect the largest statistics of neutrino interactions, enabling the resolution of anomalies which could be caused by additional neutrinos, cross-section measurements in many relevant channels for SBN and DUNE, and Beyond-Standard-Model (BSM) searches. The goal of this fellowship is for Dr Crespo to make a high-visibility contribution to SBND at CIEMAT. Specifically, the objectives are 1) commission the data acquisition and trigger systems of SBND, a critical contribution to the experiment; 2) develop the simulation and reconstruction of scintillation light in the detector, which is crucial for the cosmic-ray background rejection in a near-surface experiment like SBND; 3) develop a search for BSM Heavy Neutral Leptons, which could explain the smallness of the neutrino mass, using the Fermilab neutrino beam. Dr Crespo will receive first-hand training by the CIEMAT group, which has broad experience in simulating and reconstructing scintillation light in LArTPCs, and led this work for one of the DUNE prototypes. The supervisor, Dr Gil-Botella, is the Leader of the Far Detector Dual-Phase Photon-Detection System for DUNE. Dr Crespo will strengthen the CIEMAT contribution to SBND. He is a member of SBND since 2015, and is an expert in the readout and trigger systems, and the Co-Convener of Astroparticle and Exotic Physics in MicroBooNE, another SBN experiment. This project will reintegrate Dr Crespo in the EU, bringing his expertise, and fostering EU and US collaboration.


Participants :
- Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (Espagne) — Coordinator, beneficiary, Recherche, subvention : 172932.48 €
Projet BACCO (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Neutron stars, black holes and white dwarfs, collectively known as compact objects, are born when normal stars die. Besides being of broad interest in astronomy, compact objects offer unique tools for the study of nuclear physics and cosmology. The density in the core of neutron stars exceeds that of an atomic nucleus, which makes them the densest stable objects that we can observe in the Universe. When accreted matter falls onto the surface of a neutron star or a white dwarf, it is piled up and compressed, becoming fuel for nuclear reactions. Despite significant progress during the last decades, fundamental questions about the physics of neutron stars, white dwarfs and thermonuclear burning remain unanswered. During this Fellowship, the Researcher will compare recent burst discoveries with numerical simulations performed in collaboration with the Host Group, in order to answer crucial open questions at the crossroads between compact objects and thermonuclear burning. The multi-disciplinary approach of this project, which combines X-ray astronomy, nuclear physics and hydrodynamic simulations, will provide the Researcher with new and valuable skills.

Mots clés : neutron stars, white dwarfs, thermonuclear burning

Participants :
- Universitat Politècnica de Catalunya (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 158121.6 €
Projet TISSUENEU (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neutrophils follow daily cycles of release from and migration back into the bone marrow, where they are eliminated. After searching for the presence of neutrophils across multiple tissues of healthy mice under steady state, my host laboratory found neutrophils in most of the tissue analyzed. These findings require the study of the role of neutrophils in their tissue of destination. Several studies have shown that neutrophil clearance might be a significant source of homeostatic signals able to functionally modulate the tissues and organs where they are eliminated. In addition, specific functions for neutrophils in the spleen have already been described. I hypothesize that neutrophils may have important roles for the homeostasis and functioning of the tissues that they infiltrate, and that they acquire tissue-specific phenotypes that favor their local functions. To understand neutrophil homeostatic functions within the tissue, I will first characterize the transcriptome of 7 different subsets of neutrophils population from intestine, lung, muscle, skin, spleen, blood and bone marrow by RNA-sequencing. In addition, to investigate weather neutrophil heterogeneity within the tissues is a stochastic or a tissue-educated mechanism I will perform single cell RNA sequencing (sc-RNA-seq) of blood neutrophils to characterize the presence of a neutrophil tissue-specific signature in the blood. Moreover, I will combine next generation sequencing techniques with the use of different transgenic mouse models to uncover tissue specific regenerative functions of neutrophils in the skeletal muscle and the skin. Results obtained in this proposal aim to challenge the classical conception about neutrophils as a homogenous population of terminally differentiated cells with functions restricted to inflammation and to explore their hetroogeneity and expand our knowledge about their specific functions during tissue homeostasis.

Mots clés : neutrophils, tissue homeostasis, immune regulation of the stem cell niche, tissue specific immune functions, tissue regeneration

Participants :
- Ministry of Health (Espagne) — Coordinator, beneficiary, Recherche, subvention : 158121.6 €
Projet OPN-Can (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

New fields are rapidly emerging that provide exciting and unforeseen opportunities to target disease. This is especially relevant for difficult-to-treat tumours where, despite decades of promising research, successful clinical translation of therapeutic options remains intractable. The interrelated fields of mechanobiology and biomimetic engineered disease models have come to the fore in the last decade1–3 and provide a range of opportunities to investigate therapeutic modalities4. These fields have implications for cancer research in three major aspects: 1) dissection of the cell biology governing microenvironmental sensing; 2) development of biomimetic platforms that enhance both the relevance (accuracy) of experimental models and our understanding of tumour biology, especially at the level of microenvironment and cell signalling; and 3) creation of analysis tools to quantify cell sensing. In this MSCA Global Fellowship, I propose a formative advanced research training period at one of the world’s leading institutions of cell and molecular biology and bioengineering (UCB) to learn and apply state-of-the-art biomimetic platforms for a novel tumour biology research project investigating osteopontin(OPN)-CD44 in mechanosensitive glioblastoma invasion. This interdisciplinary collaboration will match the expertise of UCB in biomimetic tumour invasion modelling of the biomechanical and biochemical properties of glioblastoma with my expertise in matricellular biology developed through my prior postdoctoral studies of osteopontin in liver disease. On my return to Europe at KCL, this will provide a springboard to establish an innovative independent research program in promising and underinvestigated tumour biology. I will transfer the knowledge learned at UCB to establish to investigate hepatocellular carcinoma invasion with biomimetic models. This work will ultimately benefit the development of anti-invasive adjuvant therapies.

Mots clés : osteopontin, tumour invasion

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 251857.8 €
- University of California System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet AdvancedStarForm (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

New stars form within large turbulent complexes harboring several thousands of solar masses of cold gas: the molecular clouds. The diffuse gas collapses gravitationally and heats up via compression until nuclear fusion reactions ignite and the star comes to life. The full description involves an intricate interplay between large-scale environmental factors and small-scale processes close to the star, connecting a number of physical mechanisms, including magnetic fields, self-gravity, radiative transfer, and time dependent chemistry. The aim of the project is to construct a unified description of star formation, from large to small scales, using the world's most advanced numerical physics. A two-way approach will be used: the global approach (I) will deal with the dynamics of interstellar gas on the turbulent cloud scale, while the local approach (II) will concentrate on the formation of the protostellar seed. The objectives are: - Ia. Carry out a parameter study of the effects of cloud mass, turbulence, radiative transfer, and magnetization on stellar populations in giant molecular clouds - Ib. Create a realistic model for protostellar radiative and outflow feedback and examine its effects on the star formation efficiency - Ic. Quantify the effects of supernova-triggered star formation - IIa. Simulate the formation of single protostars using extremely detailed physics (non-ideal MHD, multi-frequency radiative transfer) - IIb. Incorporate for the first time into the simulations a chemistry module which interacts with the gas and radiation field - IIc. Study episodic accretion events in protostars to try and explain under-luminous young stellar objects. This is an ambitious, strongly multidisciplinary program, which fits perfecty in the research activities of the host institute. To ensure the project's success, I have a proven record of working with the different numerical techniques required, as well as an excellent understanding of astronomical observations.

Mots clés : star formation, computational astrophysics, radiation hydrodynamics, magnetic fields, astro chemistry

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet PVB-ASD (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Social Sciences and Humanities
Statut du projet : CLOSED

New theories of Autism Spectrum Disorders (ASD) based on Predictive Coding have been proposed in recent years. These theories are motivated by the increasing empirical support for predictive coding models of the brain and the unprecedented amount of autism symptoms that can be explained by this framework. Recently, Van de Cruys et al. (2014) proposed the "High Inflexible Precision of Prediction Errors in ASD" theory, suggesting that individuals with ASD have difficulties in differentiating random variability from relevant learnable regularities in the world, and that this may explain their peculiar behaviour in cognitive and perceptual tasks as well as some of their affective issues. This could be rooted in altered meta-learning processes (learning about what is "learnable"). However, empirical investigations of some of the theory’s critical hypotheses are missing. Here we assess these hypotheses using neuroimaging methods (EEG and fMRI) and tasks that integrate attention orienting, probabilistic learning and perceptual organization in vision. Specific objectives: A- Investigating if meta-learning processes are affected in ASD and which neural networks are involved. B- Understanding where and when these mechanisms are altered in the hierarchy of visual information processing. C- Identifying potential neural markers of ASD and relating these to individual differences. This theory was proposed by the host lab. It currently develops state-of-the art multidisciplinary investigations bridging basic and clinical research. However, the lab lacks a researcher with both clinical and neuroimaging expertise at the moment. My expertise will be critical in integrating these lines of research and assessing their theory. During the fellowship I will gain new neuroimaging research skills and improve my ability to integrate theoretical models with clinical research. The university will host ECVP 2019, a unique opportunity for networking, dissemination and learning of management.

Mots clés : autism, predictive coding, attention, perceptual organization, fmri, predictive processing, meta learning

Participants :
- KU Leuven (Belgique) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172800.0 €
Projet AlgCoustics (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Next generation biomass resources such as marine seaweed and micro-algae have advantages in comparison to terrestrial lignocellulosic biomass as they can grow on non-arable land at higher areal productivities. Aquatic biomass can provide renewable energy (e.g. biodiesel, bioethanol and biogas) as well as high-value molecules such as carotenoids, fatty acids, carbohydrates, proteins and food fibres, which can be used in food, feed, cosmetics, biomaterials, nanostructures and pharmaceutical industries. However, in order to greatly increase the economic viability of aquatic biomass, all components found in the biomass need to be valorized. Unfortunately, valorization of multiple biomass components is not possible using current/conventional biorefinery technologies, where up to 90% of the biomass is being treated as a waste. The value of these broken-down compounds sees more than a ten-fold reduction, rendering the biorefinery economically unfeasible. Therefore, in furtherance of developing multiproduct biorefineries, selective and economically feasible extraction and separation technologies will need to be developed and implemented. Significant microalgal cell disruption and extraction advances have been recently made by employing external fields such as lasers, ultrasonic waves and microwaves, in combination with less aggressive solvents and ionic liquids. However, the issues regarding the use of chemicals and multiple separation stages remain. Thus, we are proposing a game-changing single-step disentanglement and separation of microalgal high-value components by using acoustic waves at different frequencies allowing thus a complete process fine-tuning and eliminating the need for chemicals. Moreover, by including our previously-developed ultrasound disruption technology, the whole cell breakdown, extraction and separation steps could be reduced to one single process governed and finely-tuned through the employed frequency ranges.

Mots clés : algal biorefineries, ultrasonic disentanglement, fractionation, acoustophoresis

Participants :
- Wageningen University & Research (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187572.48 €
Projet nAChRs-CRC-PCa-IF-RI (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : TERMINATED

Nicotinic acetylcholine receptors (nAChRs) are transmembrane ligand gated ion channels composed of five subunits and encoded by 16 genes. Depending on the subunit composition nAChRs have different properties and functions. It is widely accepted that smoking tobacco is correlated with several types of cancers and that nicotine and tobacco-derived nitrosamines are known to activate nAChRs contributing to oncogenic processes. To date the question of whether nAChRs contribute to the cellular malfunctions involved in prostate and colon cancer still remains unanswered. Our preliminary results show for the first-time different expression levels of nAChRs subunits in prostate and colon cancer cell lines. Most strikingly is the clear difference of expression of nAChRs subunits between cancerous vs. non-cancerous cells, depending on the aggressiveness and cell type. The question arises whether these differences have a physiological impact. In the present project I will investigate the pathophysiological role of nAChRs in prostate and colorectal cancer. My aim is to (1) Identify and characterize nAChRs involved in prostate and colon cancer; (2) study the role of nAChRs in migration, proliferation and invasion in prostate and colon cancer; (3) the influence of a duplicated isoform of the α7 nAChR subunit, dupα7, and its anti-angiogenic properties in CRC and PCa; and (4) the role of chemotherapeutic drugs, which could augment nAChRs expression in cancer and contribute to chemoresistance. The present project will be performed at the laboratory of Dr. Peinelt University of Bern, an established research group with a focus on the pathophysiology of ion channels in prostate and colorectal cancer and in collaboration with the Urology Department of the University Hospital Inselspital Bern. The Marie Curie IF will help me to further develop leadership skills, scientific maturity and independence and will be crucial for my aim to obtain an independent academic position in the future.

Mots clés : nicotinic acetylcholine receptors, ion channel, cancer, prostate cancer, colon cancer, pharmacology

Participants :
- University of Bern (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203149.44 €