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

Neural correlates of goal-directed behavior have been extensively studied with functional Magnetic Resonance Imaging (fMRI). This has allowed identifying the functional specialization of subregions in prefrontal cortex (PFC). In particular, medial PFC (MPFC) is involved in error monitoring, cognitive control, reward prediction and motivation, while dorsolateral PFC (DLPFC) supports working memory and goal-maintenance. Though useful, such characterization has neglected one fundamental aspect: network interactions. A mechanistic understanding of how MPFC and DLPFC interact in orchestrating goal-directed behavior is still lacking. Both regions seem to be involved in both prediction and error signalling mechanism, and in motivation-driven task-preparation. To date, no theoretical account has reconciled these findings, nor explained how MPFC and DLPFC interact in producing such effects. Here we propose a novel framework, where error signals generated by MPFC train error representations in DLPFC. These representations are reactivated when the same circumstance recurs and drive proportional MPFC involvement to prevent the error from happening again (by deploying adequate neural resources). The goal of the project is to test this theory by combining the excellent spatial resolution of fMRI with the excellent temporal precision of EEG in conjunction with precise quantitative predictions based on computational models of PFC. Simultaneous EEG-fMRI recordings will allow testing PFC network dynamics, both in a simple sensory prediction paradigm, and in a paradigm modulating motivation, aiming at demonstrating a shared underlying principle. This research programme will provide a neurofunctional characterization of how PFC network interactions drive goal-directed behaviour in both prediction and motivated task engagement. This work has important implications for future studies on PFC both in healthy subjects and in patients with motivation disorders.

Mots clés : cognitive neuroscience, simultaneous eeg fmri, mpfc, dlpfc, prediction, motivation, error, computational modeling, network

Participants :
- Radboud University Nijmegen (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165598.8 €
Projet CREST UNDER TENSION (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : TERMINATED

Neural crest cells (NCC) are a unique vertebrate-specific population of multipotent cells that contribute to the development and evolution of the vertebrate head. During embryonic development, cranial NCC give rise to a variety of hard and soft tissue cells including osteoblasts, chondrocytes, odontoblasts, glia and neuronal cells. Whilst we understand a great deal about how growth factors and soluble chemicals determine the generation, migration, proliferation, survival and differentiation of the neural crest, nothing is known about how mechano-regulatory factors influence NCC fate. Recent evidence has shown that mesenchymal stem cell fate and cell behaviours are controlled by mechano-regulatory signals via the actinomyosin skeleton, and the co-transcriptional effectors, Yap and Taz. Given that NCC are similarly exposed to different mechanoregulatory influences from stiff and soft matrices and tensions generated by the differential growth and morphogenesis of adjacent epithelial and mesenchymal structures, it is hypothesized that NCC differentiation is also mechano-regulated. This proposal will use in vitro and in vivo approaches to test this hypothesis and determine if NCC fate is governed by mechano-regulatory signals, the differential regulation of the actinomyosin skeleton and Yap/Taz. The proposal will provide novel insight into the mechanisms of embryonic cell differentiation and craniofacial birth defects. Additionally, as neural crest stem cells have been identified in the adult, it will provide an understanding of how these may be manipulated to generate specific cell populations for tissue repair. The proposal will test a novel hypothesis and provide research training in a unique interdisciplinary skill set encompassing biology and engineering at the forefront of research field in addition to transferable skills. The Fellow will be mentored by two internationally recognised supervisors, who are experts in developmental biology and engineering.

Mots clés : developmental biology, cell biology, mechanotransduction, neural crest cells

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

Neural tube closure (NTC) is a fundamental process during vertebrate embryogenesis, which leads to the formation of the central nervous system. Defective NTC leads to neural tube defects (NTDs), which are one of the most common human birth defects. During NTC Convergent Extension (CE) leads to the narrowing and elongation of the neural plate (NP) and Apical Constriction (AC) drives the bending of the tissue. While the role of the aforementioned morphogenetic events for NTC has been studied extensively how the development of tissues mechanically coupled with the NP affects NTC remains poorly understood. Here, we aim to elucidate the influence of surface ectoderm (SE) and somitic mesoderm (SM) morphogenesis on NTC. To achieve our goals, we will employ an interdisciplinary research plan using Xenopus laevis and mouse embryos as model systems. First, to understand the contribution of SE and SM morphogenesis on NTC (AC and CE) we will specifically inhibit these processes using morpholino mediated protein knock-down in Xenopus embryos and tissue-specific knock-out and knock-in models in mice embryos. Subsequently, we will directly assess the impact of SE and SM tissue tension on NTC by modulating tissue tension in Xenopus embryos through optogenetic tools and mutant constructs in conjunction with live imaging. We will go on to examine how SE and SM influence the mechanical landscape of the NP using force inference techniques in Xenopus and mouse embryos in conjunction with loss of function approaches described above. Finally, we will examine how mechanical coupling between the NP with both the SE and SM affects the mechanosensitive elements responsible for CE and AC. Overall the data produced by the proposed work will uncover the role of SE and SM morphogenesis on NTC expanding our understanding of human NTDs, while at the same time providing precious insights with respect to the coordination and coupling of mechanical force generators during embryonic development.

Mots clés : neural tube closure, apical constriction, convergent extension, xenopus, mouse, embryogenesis

Participants :
- University of Cyprus (Chypre) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 157941.12 €
Projet STOICISM (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Neurodegeneration, such as Alzheimer’s disease, currently affects 15 million people in the US with a death rate of 29.5% among 65+ years old and produces a cost around 200 billion dollars per annum. These type of pathologies are caused by neuronal communication failures in multi-scales of the cortical microcolumns. Neuroscience has historically provided theories and experiments to explain the signal propagation and neurodegeneration inside cortical microcolumns, but these behaviours are far from being fully explained. The newly formed research area of molecular communications can bring light to this challenge by using information and communication theory in this scenario. A novel interdisciplinary methodology (multi-scale modelling + neurological modelling + information theory) can analyze and quantify the dynamics in the synaptic plasticity and provide further understanding about cortical microcolumns. With this approach, STOICISM project aims to i) model the multi-scale cortical microcolumn neurology; ii) model and quantify the neuronal communication; iii) investigate the long-term plasticity dynamics and control strategies. STOICISM will develop a complete in-silico model of the 2mm cortical microcolumn that will account for its multi-scale communication. The synaptic plasticity variation will be modelled as a stochastic model based on in-vitro experimentation of the neuron-astrocyte communication. This action requires the researcher to move to a world-center in computational biophysics, such as BioMediTech, where he can get appropriate training, perform biological experiments and collaborate with other top researchers while being supervised by the renowned leading academic Prof. Jari Hyttinen. STOICISM will change the way we understand the effects of neurodegeneration which will enable future non-invasive detection and drug discovery, potentially creating a longer-term impact on the ageing society.

Mots clés : molecular communications, multi scale modeling, information theory, neuron astrocytes, cortical, microcolumns, synaptic plasticity

Participants :
- Tampere University (Finlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 202680.96 €
Projet SYNPARK (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neurodegenerative diseases affect more than 6 million people in Europe, and its prevalence is growing as population ages, hence it is a timeliness health challenge we are facing as a society. Parkinsonism is the 2nd most prevalent neurodegenerative form, being Parkinson’s disease (PD) the most frequent, whereas 20% of the patients are diagnosed with atypical parkinsonisms (AP). Despite presenting some clinical overlap, AP tends to be more therapy-resistant and have faster degeneration rates than PD. SYNPARK is an interdisciplinary project that will investigate the discriminative power of different imaging markers’ modalities in parkinsonisms. Improving diagnostic accuracy is crucial as disease-modifying therapies are becoming available for PD. For this challenge, I propose a multidisciplinary approach: from the in-vivo synaptic molecular brain assessment (using positron emission tomography, PET), the whole-brain connectomics organisation (using magnetic resonance imaging, MRI) to the clinics. I will conduct the outgoing phase in one of the world’s PET leading centres in Toronto to test the clinical validity of a new generation PET tracer in AP/PD. My host return institution (Barcelona) has pioneered the research on machine learning (ML) techniques that are revolutionising the medical sciences field to improve parkinsonisms’ differential diagnosis at the single-patient level by means of whole-brain MRI connectomics information. My current expertise and the proposed ambitious training objectives will position me at the forefront of this exciting new avenue in medical sciences and will enhance my professional independence for research leadership. Overall, the synergies established between these two leading centres are expected to have a tremendous impact on the understanding of AP/PD brain pathophysiology and its diagnostic accuracy, and ultimately enhancing a revolution in personalised medicine, a futuristic therapy that is increasingly becoming a reality.

Mots clés : structural mri connectivity, functional mri connectivity, positron emission tomography, atypical parkinsonism

Participants :
- University of Barcelona (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 232497.6 €
- Centre for Addiction and Mental Health (Canada) — Partner, organization partner, Autres, subvention : 0.0 €
Projet NeuroMOF (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Neurodegenerative diseases severely affect patients’ health resulting in poor quality life and significant impact on global healthcare costs. The mayor challenge is the bypass of the blood-brain barrier (BBB), limiting the diffusion of therapeutic cargo to the central nervous system (CNS). Although emerging technologies based on nanomedicine (liposomes, polymers, etc.) are a promising approach to overcome the BBB, their clinical application is still limited by their lack of in vivo efficacy. In view of this scenario, a new class of nanoscaled porous Metal-Organic Frameworks (nanoMOFs) has attracted great attention in the biomedical domain. NanoMOFs present several advantages compared to classic nanocarriers: i) their chemical & structural versatility, allowing a suitable biocompatibility and the potential control of their in vivo fate, ii) exceptional loading of challenging ingredients (cosmetics, enzymes, drugs...) together with controlled release under physiological conditions; iii) green and scalable synthesis; iv) lack of in vitro & in vivo toxicity; v) interesting imaging properties. Latest biomedical advances have been focussed to tackle typical administration routes (e.g. oral, intravenous or cutaneous). However, the targeted delivery to the brain has not been under the spotlight within the scientific community. Thus, the aim of this proposal is to develop a biosafe and efficient nanoMOF platform for brain delivery. Two original strategies will be undertaken to overcome the BBB: targeting by external functionalization with BBB-specific ligands & enzyme immobilization (self-propelled nanomotors), facing up the challenge to control the orientation, stability, density and distribution (symmetric/asymmetric) of the surface agent. Apart from a full physicochemical characterization of these prototypes, BBB crossing will be first assessed by simple and 3D in vitro models and finally, by preliminary in vivo assays.

Mots clés : self propulsion, autonomous, engineered nanomofs, targeting, neurological disease, brain

Participants :
- Madrid Institute for Advanced Studies (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet Degradation_ID (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neurodevelopmental disorders (NDDs) are genetically extremely heterogeneous with mutations in more than 1000 genes being causative. NDD-related genes and encoded proteins are involved in a wide range of various biological processes. Recently, several genes involved in protein degradation have been implicated in NDDs. This suggests that defects in protein homeostasis may be a recurring theme in neurodevelopment and cognition. We have recently identified de novo mutations in the nuclear E3-ubiquitin ligase complex component FBXO11 in 20 patients with a variable neurodevelopmental disorder. Loss-of function or haploinsufficiency of FBXO11 is the most likely mechanism for FBXO11-related NDDs. The pathomechanism of how FBXO11deficiency may lead to (neuro)-developmental defects has yet to be established. The objective of this project is to understand the role FBXO11 defects may play in the development of NDDs. In aim 1 I will focus on deciphering the molecular function of FBXO11 using two complementary approaches: identifying FBXO11 substrates using affinity-purification mass-spectrometry approaches and identifying pathways affected by FBXO11 dosage alterations using transcriptomic approaches. The identification of FBXO11 substrates and downstream pathways will lead to a better understanding of its role in neurodevelopment and in NDDs. In aim 2 I will characterize the role of Fbxo11 in neurodevelopment by modeling Fbxo11 deficiency in Drosophila melanogaster and investigate the potential to manipulate phenotypes by supplementation of fly food with proteasome activators. Collectively, this project will furthermore open a window to better understand the role alterations of protein degradation may play for NDDs in general.


Participants :
- Universitätsklinikum Erlangen (Allemagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 131104.8 €
- University of Bern (Suisse) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 43701.6 €
Projet NVU-Chip (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Statut du projet : CLOSED

Neurological disorders affect many people's life, contributing to significant mortality and morbidity in the modern world, with 16.5% of global deaths and are the leading cause of disability, affecting 276 million people's daily lives. Many of these diseases, including Alzheimer’s and Multiple Sclerosis, are related with the impaired blood-brain barrier (BBB) function. Unfortunately, neither animal models of the neurovascular unit (NVU) nor in vitro cultures of primary or immortalized human brain microvascular endothelial cells (BMVECs) alone effectively mimic the barrier, and transporter functions of the BBB observed in humans. Thus, there is a great need for human NVU models to recapitulate in vivo human physiology in health and disease conditions and understand the cellular mechanisms and changes in disease conditions. This project aims to develop a 3D NVU model to identify the cell-type-specific responses to diverse inflammatory stimuli in the NVU. The NVU-Chip project will the first model providing such a complex cellular environment in a unique microfluidic device to fully recapitulating human NVU in vitro utilizing relevant mechanobiological forces. Additionally, The NVU-Chip will improve the state-of-the-art by incorporating cyclic mechanical strain in a BBB model for the first time. This project will combine and amend the state-of-the-art stem cell technologies to differentiate all brain cells, and advanced microfabrication approaches to design and fabricate the microfluidic chips using the most appropriate materials ECM coatings for co-culturing all cell types in the same device. The human-based NVU-Chip model will also give a new approach for studying cellular responses to diverse inflammatory stimuli, identifying key inflammatory factors of CNS related diseases. Outcomes of the NVU-Chip project will enhance the existing knowledge and technologies, yielding high-impact journal publications, as well as potential commercial product in the long term.

Mots clés : organ on a chip, neurovascular unit, microfluidic device design, mechanobiology, inflammation, immune response, cellular interaction, induced pluripotent stem cells, brain diseases

Participants :
- Sabancı University (Turquie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 157355.52 €
Projet STEM ZAP (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neurological disorders, such as multiple sclerosis (MS), that involves degeneration of the myelin sheath exact a social and economic toll on the EU estimated at 14.6 billion Euros per year. Consequently therapies capable of regenerating damaged myelin are an important clinical goal. The aim of this fellowship is to develop new strategies for the replacement of myelin through the use of embryonic stem (ES) cells. We propose to achieve this aim by identifying novel signalling molecules capable of enhancing the generation of myelin-forming oligodendrocytes from ES cells. Membrane depolarisation enhances myelination during postnatal development, and can promote the differentiation of ES-OL cells. However, the impact of depolarisation on the generation of oligodendrocytes from ES cells (ES-OL) is unknown, as are the signalling molecules driving depolarisation-induced ES cell differentiation. Filling these gaps has the potential to deliver new methods for increasing the supply of pro-myelinating ES-OL capable of regenerating damaged myelin. This fellowship will unite supervisor Dr Fulton’s expertise in oligodendrocyte biology and optogenetics with Dr Otsu’s knowledge and skills in novel methods for the efficient production of ES-OL. In addition, partner organisations from the commercial and clinical sectors will add additional expertise that will enhance the project’s research capacity, and ensure success in its goal of developing novel pathways towards myelin regeneration.

Mots clés : optogenetics, oligodendrocyte precursor cell, myelination, multiple sclerosis

Participants :
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet SYNPT (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Neuronal communication primarily occurs at synapses. Recent studies have suggested a key role for protein synthesis and degradation in the regulation of synaptic structure, function and plasticity by changing the abundance of select synaptic proteins in a spatially confined manner. Remodeling of the synaptic proteome is accomplished by, for example, regulated degradation via the ubiquitin proteasome system or by autophagy. Autophagy has been shown to modulate synaptic vesicle numbers and neurotransmission, yet its exact role in the regulation of synaptic function is poorly understood. The proposed project aims at the dissection of the role of autophagy in synaptic protein turnover. Using combined genetic, biochemical, molecular and cellular biology approaches as well as cutting-edge imaging in neurons I will identify presynaptic proteins that are regulated by autophagy and will define the contribution of autophagy to synapse composition and function. Furthermore, I will determine which mechanisms underlie the selective targeting of presynaptic proteins to the autophagy pathway. Taken together these studies will contribute fundamental knowledge about autophagy in neurons and will provide new insights for understanding how autophagy contributes to synaptic plasticity and protein degradation in health and disease.

Mots clés : synaptic plasticity, presynapse, autophagy

Participants :
- Forschungsverbund Berlin (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 159460.8 €