Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : BREATHE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497125.0 €

Surfactant Protein B (SP-B) deficiency and Cystic Fibrosis (CF) are severe, fatal inherited diseases affecting the lungs of ten thousands of people, for which there is currently no available cure. Although gene therapy is a promising therapeutic approach, various technical problems, including numerous physical and immune-mediated barriers, have prevented successful application to date. My recent studies were the first to demonstrate the life-saving efficacy of repeated pulmonary delivery of chemically modified messenger RNA (mRNA) in a mouse model of congenital SP-B deficiency. By incorporating balanced amounts of modified nucleotides to mimic endogenous transcripts, I developed a safe and therapeutically efficient vehicle for lung transfection that eliminates the risk of genomic integration commonly associated with DNA-based vectors. I also assessed the delivery of mRNA-encoded site-specific nucleases to the lung to facilitate targeted gene correction of the underlying disease-causing mutations. In comprehensive studies, we show that a single application of nucleases encoded by nucleotide-modified RNA (nec-mRNA) can generate in vivo correction of terminally differentiated alveolar type II cells, which more than quadrupled the life span of SP-B deficient mice. Together with my working group, I aim to further develop this technology to enhance the efficiency and safety of nec-mRNA-mediated in vivo lung stem cell targeting, providing an ultimate cure by permanent correction. Specifically, we will test this approach in humanized mouse models of SP-B deficiency and CF. Developing and genetically engineering humanized models in vivo will be a critical step towards the safe translation of mRNA based nuclease technology to the clinic. With my competitive edge in lung-transfection technology and strong data, I feel that my group is uniquely suited to achieve these goals and to make a highly valuable contribution to the development of an efficient treatment.

Mots-clés : modified messenger rna,in vivo gene correction
Projet ERC : MAT_STOCKS (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Klagenfurt — Pays : Autriche — Rôle : Partner
Acronyme de l'entité : AAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Sustainability transformations imply fundamental changes in the societal use of biophysical resources. Current socioeconomic metabolism research traces flows of energy, materials or substances to capture resource use: input of raw materials or energy, their fate in production and consumption, and the discharge of wastes and emissions. This approach has yielded important insights into eco-efficiency and long-term drivers of resource use. But due to its focus on flows, socio-metabolic research has not yet incorporated material stocks or their services, thereby not fully realizing its analytic potential. MAT_STOCKS addresses this gap by developing a consistent typology, indicators and databases of material stocks and their services, building upon economy-wide material flow analysis. It will create a comprehensive, global, national-level, validated material stocks and services database as well as maps of material stocks from remote-sensing data. This will allow analyzing the stock/flow/service nexus and underpin highly innovative indicators of eco-efficiency overcoming limitations of current approaches which mainly relate resource use or emissions to population and GDP. New insights on stock/flow/service relations, the relevance of spatial patterns and options for decoupling will be used to create a dynamic model to assess option spaces for transformations towards sustainable metabolism. MAT_STOCKS will identify barriers and leverage points for future sustainability transformations and the SDGs, and elucidate their socio-ecological and political implications. Our preliminary analyses suggest that unravelling the stock/flow/service nexus provides a crucial missing link in socio-metabolic research because it explains why, how and where patterns of material and energy use change or remain locked-in. Thereby, important analytical insights will be introduced into the largely normative and local discourses on the transformation towards a sustainable society.

Mots-clés : socioeconomic metabolism,social ecology,material flow analysis,energy flow analysis
Projet ERC : MAT_STOCKS (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Humboldt-Universität zu Berlin — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : HU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 529375.0 €

Sustainability transformations imply fundamental changes in the societal use of biophysical resources. Current socioeconomic metabolism research traces flows of energy, materials or substances to capture resource use: input of raw materials or energy, their fate in production and consumption, and the discharge of wastes and emissions. This approach has yielded important insights into eco-efficiency and long-term drivers of resource use. But due to its focus on flows, socio-metabolic research has not yet incorporated material stocks or their services, thereby not fully realizing its analytic potential. MAT_STOCKS addresses this gap by developing a consistent typology, indicators and databases of material stocks and their services, building upon economy-wide material flow analysis. It will create a comprehensive, global, national-level, validated material stocks and services database as well as maps of material stocks from remote-sensing data. This will allow analyzing the stock/flow/service nexus and underpin highly innovative indicators of eco-efficiency overcoming limitations of current approaches which mainly relate resource use or emissions to population and GDP. New insights on stock/flow/service relations, the relevance of spatial patterns and options for decoupling will be used to create a dynamic model to assess option spaces for transformations towards sustainable metabolism. MAT_STOCKS will identify barriers and leverage points for future sustainability transformations and the SDGs, and elucidate their socio-ecological and political implications. Our preliminary analyses suggest that unravelling the stock/flow/service nexus provides a crucial missing link in socio-metabolic research because it explains why, how and where patterns of material and energy use change or remain locked-in. Thereby, important analytical insights will be introduced into the largely normative and local discourses on the transformation towards a sustainable society.

Mots-clés : socioeconomic metabolism,social ecology,material flow analysis,energy flow analysis
Projet ERC : MoMa-STOR (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2990937.5 €

Sustainable energy generation by water, wind, and solar has reached in the EU a mature and economic state, but further growth to tackle the climate crisis has faltered because more economic, scalable and sustainable energy storage concepts are missing. The groups of both PIs have a proven track record in this area but, interestingly they were able just recently to perform first experiments indicating big potential gains in performance. The Simon group identified a specific ion organization in nanoporous carbon electrodes leading to enhanced capacity. He also evidenced fast, new pseudocapacitive redox contribution in metal carbides of still unclear origin. The Antonietti group could not only build from oxidation stable noble carbons a 6.5 Volt supercapacitor, but also show that in those new device major storage peaks come from solvent structure changes. In another work, massive sub-potential deposition of Na-metal was observed is the Schottky transition layers of hybrid materials, thus making sodium batteries potentially save and efficient. The general aim of MoMa-STOR is to address such fundamentally new, non-classical and non-technically covered modes of energy storage and to develop the related materials base for them, to design the next generation of energy storage devices. These new modes include a) energy storage by desolvation and matrix change, b) reversible high energy bulk structure transition, and c) metal-metal and metal-semiconductor heterojunction interface effects. New modes will be carefully analysed with advanced electrochemical techniques, including quartz crystal microbalance, differential electrochemical mass spectroscopy, combined with in situ X-ray and Raman spectroscopy for instance, to gain a precise physico-chemical picture of the operation principles. In operando high resolution electron microscopy and EELS will complete the molecular understanding of the processes.

Mots-clés : electron storage,low dimensional nanomaterials,supercapacitor,ionic liquid,in operando analytics
Projet ERC : MoMa-STOR (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Université de Toulouse — Pays : France — Rôle : PI
Acronyme de l'entité : UT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2661274.11 €

Sustainable energy generation by water, wind, and solar has reached in the EU a mature and economic state, but further growth to tackle the climate crisis has faltered because more economic, scalable and sustainable energy storage concepts are missing. The groups of both PIs have a proven track record in this area but, interestingly they were able just recently to perform first experiments indicating big potential gains in performance. The Simon group identified a specific ion organization in nanoporous carbon electrodes leading to enhanced capacity. He also evidenced fast, new pseudocapacitive redox contribution in metal carbides of still unclear origin. The Antonietti group could not only build from oxidation stable noble carbons a 6.5 Volt supercapacitor, but also show that in those new device major storage peaks come from solvent structure changes. In another work, massive sub-potential deposition of Na-metal was observed is the Schottky transition layers of hybrid materials, thus making sodium batteries potentially save and efficient. The general aim of MoMa-STOR is to address such fundamentally new, non-classical and non-technically covered modes of energy storage and to develop the related materials base for them, to design the next generation of energy storage devices. These new modes include a) energy storage by desolvation and matrix change, b) reversible high energy bulk structure transition, and c) metal-metal and metal-semiconductor heterojunction interface effects. New modes will be carefully analysed with advanced electrochemical techniques, including quartz crystal microbalance, differential electrochemical mass spectroscopy, combined with in situ X-ray and Raman spectroscopy for instance, to gain a precise physico-chemical picture of the operation principles. In operando high resolution electron microscopy and EELS will complete the molecular understanding of the processes.

Mots-clés : electron storage,low dimensional nanomaterials,supercapacitor,ionic liquid,in operando analytics
Projet ERC : SYNNOVATE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Synapses are a hallmark of the brain, showing remarkable anatomical and molecular complexity, and central to the aetiology and progression of hundreds of brain diseases. The vertebrate brain has a vast potential synapse diversity arising from the differential distribution of combinations of proteins into individual synapses. This has led to the recognition that “synaptome mapping” needs to be developed where the expression level of individual proteins is robustly measured in individual synapses across the whole brain. We developed a novel and unique ‘synaptome discovery and imaging platform’ that links the molecular organisation of synapses with the spatial and temporal anatomical diversity of individual synapses and charts molecular synaptome maps across the brain. This platform enables routine and rapid quantification of genetically encoded molecular markers, with multiple functionalities, in almost a billion synapses in hundreds of brain regions of the mouse and generates statistically robust synapse catalogues and molecular maps of the brain. We have uncovered remarkable new neuroanatomical features and revealed a synaptic molecular architecture at the systems-wide scale. We have discovered this architecture is radically reorganised by mutations that cause schizophrenia, intellectual disability and autism. We have also shown these new methods can label activity-dependent reorganisation of single synapses at a whole brain scale, enabling the tracing of synaptic memory engrams. Our goals are to understand how synaptome maps develop and are reorganized by mutations causing cognitive disorders; examine experience-dependent map plasticity during development, following learning and electrophysiological stimulation in normal animals and those carrying cognitive disorder mutations. We also plan to develop computational approaches based on synaptome maps and freely distribute genetic and image analysis tools to promote synaptome mapping in the community.
Projet ERC : CellCellEM (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499885.0 €

Synapses are intercellular junctions specialized for coordinated cell-cell communication throughout the nervous system. They are organized by cell-adhesion molecules (CAMs) that bi-directionally orchestrate neuronal communication. Latrophilins (LPHNs) are a unique sub-family of CAMs that play critical roles in structuring the synaptic architecture through multifaceted interactions with a large variety of synaptic partners. Mutations in LPHN have been associated with neurodevelopmental and neuropsychiatric disorders. Despite their gravity, the mechanism governing LPHN synaptic activities remain elusive. To further our understanding of LPHN-mediated cell-cell communication, we suggest to characterize these receptors’ interactions with their intracellular and extracellular partners. For this purpose, we propose to adopt a hybrid approach driven primarily by cryo-EM, a state-of-the-art technique capable of dissecting the molecular mechanisms of super-molecular assemblies at extremely high spatial resolutions, which is our group’s main field of expertise. The cryo-EM studies will be complemented by cryo electron tomography (cryo-ET), fluorescence microscopy and biochemical approaches. Our specific aims are: Aim 1: Dissect the molecular mechanisms of LPHN activation by combining cryo-EM with biochemical methodologies. Aim 2: Characterize the LPHN interactome through cryo-EM and fluorescence microscopy. Aim 3: Resolve the architecture of the LPHN interactome at a close-to-native environment through cryo-ET. Our experimental strategy will generate a quantitative, near-atomic resolution view of LPHNs and the mechanism by which they interact with their synaptic partners and instigate trans-synaptic signal transduction. These data will be vital for understanding LPHN-mediated cell-cell communication as well as the mechanisms governing trans-synaptic interactions and could potentially highlight novel approaches to treat neurodevelopmental and neuropsychiatric disorders.

Mots-clés : cryo em,cryo et,gpcr,cell cell adhesion
Projet ERC : SYNAPTOME (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1738561.0 €

Synapses participate in all our thoughts and actions and are damaged in over 100 genetic brain disorders. Synapses are the hallmark of brain complexity, being present in vast numbers and containing thousands of different proteins. Unravelling this complexity to get at the functional logic embedded within is a major challenge in neuroscience. We recently characterised excitatory synapse molecular diversity across the whole mammalian brain, revealing a remarkable 3D organisation of synapse types across the different regions – the ‘synaptome architecture’. This architecture is reorganised in genetic diseases, is important in structural and functional connectivity across the brain, and provides a mechanism for the storage and recall of information. But what of the fundamental, functional cellular building block of this architecture – the single neuron and its dendritic tree? Crucially, very little is known about the distribution of synapse types on individual neurons and what this actually means for brain function. The overarching goal of SYNAPTOME is to define single-neuron synaptome architecture (SNSA). We will develop new genetic labelling and computational approaches to systematically map SNSA in the mouse brain. We will identify the SNSA of specific functional types of neurons and determine whether neurons share a canonical SNSA. We will reveal how the SNSA is built during development and how it is relevant to the connections between neurons and their physiological properties and functional output. We will ask if the SNSA can direct us to the specific synapses damaged in genetic disorders. These studies will uncover fundamental design principles inherent in the building blocks of the brain that link genome, proteome and synaptome with the architecture and function of individual neurons and their organisation into brain-wide networks. The new tools, resources and knowledge that SYNAPTOME will bring will have wide application in neuroscience and disease research.

Mots-clés : synapse,neuron,anatomy,image analysis,synaptome
Projet ERC : C.NAPSE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université Claude Bernard - Lyon 1 — Pays : France — Rôle : PI
Acronyme de l'entité : Lyon I
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1856500.0 €

Synaptic scaffolding molecules control the localization and the abundance of neurotransmitter receptors at the synapse, a key parameter to shape synaptic transfer function. Most characterized synaptic scaffolds are intracellular, yet a growing number of secreted proteins appear to organize the synapse from the outside of the cell. We recently demonstrated in C. elegans that an evolutionarily conserved protein secreted by motoneurons specifies the excitatory versus inhibitory identity of the postsynaptic domains at neuromuscular synapses. We propose to use this system as a genetically tractable paradigm to perform a comprehensive characterization of this unforeseen synaptic organization. Specifically, this project will pursue 4 complementary aims: 1) Identify and characterize a comprehensive set of genes that organize and control the formation and maintenance of these scaffolds through a series of genetic screens based on the direct visualization of fluorescent acetylcholine and GABA receptors in living animals. 2) Solve the spatial synaptic organization of these scaffolds at a nanoscale resolution using super-resolutive and correlative light and electron microscopy, and analyze their dynamic behavior in vivo by implementing Single Particle Tracking imaging in living worms. 3) Decipher the role of the synaptomatrix in the organization of synaptic extracellular scaffolds and evaluate its functional contribution at the physiological and molecular levels using a candidate gene strategy and innovative imaging. 4) Analyze the formation and decline of these scaffolds at the lifetime scale and evaluate the role of synaptic activity and aging in these processes by taking advantage of the possibility to follow identified synapses over the entire life of C. elegans. Using powerful genetics in combination with cutting-edge in vivo imaging and electrophysiology, we anticipate to identify new genes and new mechanisms at work to regulate normal and pathological synaptic function.

Mots-clés : synapse,synaptic scaffold,acetylcholine receptor,gaba receptor,extracellular matrix,c  elegans,genetic screen,super resolutive microscopy,clem
Projet ERC : SensoNMDA (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1200000.0 €

Synaptic variability between neuronal connections is thought to contribute to brain’s remarkable information processing capacities. In the adult brain, the density as well as subunit composition of synaptic NMDA receptors (NMDARs) varies considerably between synapses and between neurons. Despite the well documented heterogeneity of NMDARs the functional relevance of such diversity is poorly known. In the past, the functional relevance of such NMDAR diversity has been mostly considered in the context of neuronal development and long-term synaptic plasticity. Model simulations have highlighted that dendritic computations are strongly influenced by synaptic NMDARs densities and biophysical properties. Here I propose to directly study the consequence of NMDAR diversity in shaping integration properties of single neurons in primary somatosensory cortex (S1). To achieve this I will decompose this broad question into three specific tasks. 1-Assessment of NMDAR heterogeneity in glutamatergic neurons and study how this variability shapes dendritic integration. 2-Study the impact of NMDARs in signal computation among cortical interneurons. 3-Investigate the functional relationship between endogenous NMDAR modulators and NMDAR diversity. I plan to use an array of genetic, optogenetic and pharmacological tools in combination with imaging and electrophysiological techniques to achieve the proposed objectives. Importantly, in vivo electrophysiology and two-photon imaging will be used to assess the functional relevance of NMDARs heterogeneity in single neuron computational strategies during sensory stimulation. I expect to reveal that NMDAR diversity plays a fundamental role in sensory information processing by tuning the relative recruitment of inhibitory and excitatory neurons during sensory stimuli. This work will provide an original and important data set demonstrating how NMDARs diversity provides cortical neurons with the possibility to compute complex sensory information.

Mots-clés : dendritic integration,nmda receptors,sensory information