Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : VIROME (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Liège — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499950.0 €

Symbiotic and pathogenic microbes are major environmental factors that play fundamental roles in shaping host immunity. Such dynamic interactions between commensals or pathogens and the host must be finely regulated to balance protective immune responses and induction of regulatory pathways. While frequently underestimated, immune imprinting by viruses is a key determinant for variation in disease susceptibility. Numerous evidence shows that a history of infections trains the innate immune system for the long term. Amongst the cells that are trained, monocytes are highly heterogeneous and are involved in essential biological processes such as anti-microbial activity, immunomodulation or macrophage-niche replenishment. While the current paradigm states that monocyte fate and function are driven by the local microenvironment, a recent study has shown that monocytes are primed in the bone marrow for functional properties. Here, we want to explore how and where monocyte development and function are educated by symbiotic (Murid herpesvirus 4) or pathogenic (Pneumonia Virus of Mice) viruses and with which potential outcomes for long-term immunity. To this end, we have devised three main aims. First, following infections, we will characterize monocytes and their progenitors by classical immunophenotyping, functional assays and unbiased single-cell RNA-seq in combination with ATAC-seq, to investigate in-depth how and where viruses shape monocytes and monocyte-derived cells. Second, molecular mechanism(s) underlying monocyte priming after infections will be assessed. In particular, based on literature and preliminary results, we postulate that bone marrow CD169+ macrophages could play a key role in early monocyte priming. Third, the consequences of virus-driven monocyte training will be investigated at steady state and upon heterologous challenges. Such research could provide the proof of concept that viral education of bone marrow monocytes shapes long-term innate immunity.

Mots-clés : symbiotic and pathogenic viruses,bone marrow monocyte imprinting,long term traning immunity,bone marrow cd169  macrophages,transcriptomic and epigenetic profiling,mouse models
Projet ERC : REMIND (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Lausanne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499991.0 €

Synapse loss is the major correlate of cognitive impairment in many neurodegenerative diseases. Recent literature suggests that microglia, which mediate synaptic pruning during brain development, can be responsible for synapse loss in neurodegeneration. Although the underlying mechanisms are poorly understood, growing evidence indicates that dysfunctional microglia affect synapses number and function in pathology. Genome-wide association studies reveal that the majority of risk genes associated with neurodegenerative disorders are highly expressed in microglia. While such studies clearly implicate these cells in the pathogenesis of the disease, little is known about the causal mechanisms that link microglial risk variants to loss of synapses. We will identify the molecular mechanisms involved in microglia-mediated synapse loss. We will also generate novel in vitro and ex vivo models of ‘risk microglia’, by introducing genetic variants associated with cognitive impairment –alone or in combination- specifically in microglia, taking advantage of CRISPR/ Cas9 genome editing techniques. These goals will be achieved by combining cutting-edge transcriptomics and proteomics with mouse models of intense synaptic remodelling, to reveal the unique molecular signature of ‘shaper microglia’. A multidisciplinary approach will allow the extensive characterisation of risk models, by combining metabolic analysis, synaptic phagocytosis and degradation assays, with super-resolution microscopy, and novel genetically encoded labelling methods. With the knowledge generated here, we aim at developing and validating in vivo novel drugs- and nanobodies-based approaches for effective targeting of pathological pruning. In summary, REMIND will focus on: 1) Identifying molecular players in microglial-mediated synapse loss 2) Generating ‘risk microglia’ models, to asses the role of genetic variants associated with neurodegeneration 3) Developing novel strategies for targeting prunining

Mots-clés : microglia,synapse loss,synaptic pruning,neurodegeneration,risk genetic variants,cognitive impairment
Projet ERC : MoNaLISA (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : KTH Royal Institute of Technology — Pays : Suède — Rôle : PI
Acronyme de l'entité : KTH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1725000.0 €

Synaptic function is difficult to analyze in living neurons using conventional optics, since the synaptic organelles and protein clusters are small and tightly spaced. The solution to this problem can come from the field of super-resolution fluorescence microscopy, or nanoscopy. However, the current approaches to nanoscopy are still far from reaching this goal. Single molecule-based approaches (including STORM and PALM) provide high spatial resolution, but slow recording, insufficient for live imaging. Ensemble approaches (including SSIM and STED) are able to record faster, but with poorer resolution or with high, potentially toxic, laser powers. It is currently impossible to image the same neuron for hours and days, with both high spatial (~30 nm) and temporal (10-1000 Hz) resolution, and with minimal photodamage. My aim is to fill this gap, by developing, for the first time, a microscope that combines the advantages of both single molecule-based and ensemble approaches. I will base the microscope on RESOLFT, a low-photodamage ensemble approach that I have pioneered recently. I will use line patterns to speed up the recording and 2photon-switching for 3D ability. I will combine this with sensitive detection schemes that allow single-molecule detection and counting, relying on my previous expertise with PALM and GSDIM. The new set-up, termed molecular nanoscale long-term imaging with sequential acquisition (MoNaLISA), will track neuronal organelles and proteins on different time scales, spanning from milliseconds to days, with a resolution close to the molecular scale. To obtain the first proof-of-principle results, I will address several issues still open in the synaptic transmission field, relating to synaptic vesicle recycling, biogenesis and degradation. Overall, my project will introduce a novel paradigm to imaging in the life sciences, which will enable fast and quantitative nano-imaging of cells and tissues.

Mots-clés : super resolution fluorescence microscopy,nanoscopy,imaging,synaptic vesicle,resolft,fluorescence
Projet ERC : C.NAPSE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 421875.0 €

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 : DYNADIFF (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : TU Dresden — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Synchrotron instrumentation plays a key role in the discovery of novel high performance materials. However, their application is limited to beam time available at large synchrotron facilities. The transfer of synchrotron based methods to a wider market of laboratory instrumentation poses significant market potential for SMEs and promotes accelerated materials discovery in industry. Responsive porous materials such as metal-organic frameworks are already recognized as highly selective adsorbents suitable to revolutionize separation processes by replacing established cryogenic distillation equipment in terms of enhanced energy efficiency and lower CO2 footprint. To unlock the potential of responsive porous adsorbents, industrial research departments, research institutes and academic institutions require advanced tools for analyzing dynamic solids in situ in the presence of gas mixtures in parallel to measuring mixture adsorption isotherms and diffraction patterns. DYNADIFF focuses on the development of an advanced adsorption chamber for parallelized (in situ) adsorption-diffraction analytics suitable for laboratory diffractometer adaption. The successful project completion will enable the commercialization of an advanced in situ instrument at reduced cost for laboratory use to promote the accelerated discovery and analysis of novel porous materials for highly selective and energy efficient gas separation processes and improved energy storage.

Mots-clés : gas separation,porous materials,metal organic frameworks,advanced instrumentation,responsive materials
Projet ERC : RNA ORIGAMI (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Aarhus University — Pays : Danemark — Rôle : PI
Acronyme de l'entité : AU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999935.0 €

Synthetic biology aims at re-engineering organisms for practical applications by designing novel biomolecular components, networks, and pathways. The field is expected to lead to cheaper drugs, sustainable fuel production, efficient diagnosis and targeted therapies for diseases. However, a major obstacle to achieve these goals is our limited ability to rationally design biomolecular structure and function. By contrast, the field of DNA nanotechnology has so far demonstrated an unprecedented ability to design and self-assemble well-defined molecular shapes, although the production method of thermal annealing is not compatible with cells. We have recently demonstrated a breakthrough method, called RNA origami, which allows the design of RNA molecules that fold into well-defined nanoscale shapes during their synthesis by an RNA polymerase. In this proposal I aim at extending this technology to produce RNA-protein nanostructures and at demonstrating their application in synthetic biology. My primary scientific hypothesis is that understanding the folding process during synthesis will help us to design nanostructures that can be produced in cells. I will design a general RNA-protein architecture that is compatible with folding during synthesis. I will investigate folding kinetics to be able to design and program the dynamical folding process. Based on this, RNA-protein nanostructures will be designed, expressed in cells, and verified, for the formation of the desired shapes. We will develop new functionalities by both rational design and selection approaches with the aim of obtaining multivalent-binding and switching properties. Finally, the functional RNA-protein nanostructures will be applied in proof-of-concept experiments to demonstrate efficient, multivalent targeting of subcellular structures, biosensing of a variety of intracellular analytes, metabolic channeling of biosynthesis pathways, and complex control of transcriptional networks.

Mots-clés : rna nanotechnology,bionanotechnology,biomolecular nanotechnology
Projet ERC : MIRASYS (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149190.0 €

Systemic sclerosis (SSc) is a life-threatening autoimmune connective tissue disorder of unknown cause, characterised by fibrosis of the skin and internal organs. SSc affects approximately 160.000 patients worldwide and is associated with life-long burden of disease. Early detection of SSc is currently impossible as diagnosis is typically based on a combination of late-stage clinical symptoms. Current diagnostics, however, are based on late clinical manifestations. There is a need for actionable biomarkers for early-stage diagnosis and disease monitoring. Based on proprietary ERC research specific microRNA (miRNA) profiles were found that positively correlates with clinical progression and complications of SSc. Its expression was elevated in subjects who demonstrated symptoms that can precede SSc onset by years. These findings provide strong support for the prognostic and diagnostic properties of the miRNA panel in SSc. MIRASYS has been designed to accelerate the commercialisation of a panel of highly potent miRNAs that have breakthrough diagnostic potential in SSc. MIRASYS will be used to validate these findings by setting miRNA expression level boundaries for SSc development and to incorporate these in a diagnostic assay. MIRASYS will also assess the commercial feasibility of setting-up a dedicated spin-off company to commercialise the technology. The team has analysed the IP landscape for similar approaches for SSc and no prior art on the specific miRNAs was found. In the MIRASYS ERC PoC Grant, the team will further investigate the IP position and formulate a strong IP strategy including the steps towards full Freedom to Operate. The MIRASYS team consists of experienced science and business professionals. The team has developed several business models which need to be assessed thoroughly through in-depth market research. The results need to be consolidated into a strong business plan that will be presented to investors and strategic investors.

Mots-clés : biomarkers,medical diagnostics
Projet ERC : TRADITION (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Autonomous University of Barcelona — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UAB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1454792.5 €

TRADITION aims to understand the long-term trajectory of human interaction with coastal resources and its legacy to present day small-scale fisheries in Latin America. Founded on traditional knowledge rooted in the past, small-scale fisheries are a crucial source of food and livelihood for millions of people worldwide, and play a pivotal role in poverty eradication in developing countries. A thorough recognition of the cultural and socio-economic significance of Latin American fisheries requires a temporal component that only archaeology and history can provide. TRADITION will investigate a 4000-year record of coastal exploitation in one of the world's most threatened tropical environments: the Atlantic forest of Brazil. We will draw together archaeological, palaeoecological, historical and ethnographic records to address fundamental questions that impinge upon our current understanding of the development of small-scale fisheries in this region. How did coastal economies adapt to the spread of agriculture? What was the impact of past climate and environmental changes on coastal populations? What was the impact of European colonisation of the Americas on the development of small-scale fisheries? What was the role of historical institutions and regulations in the negotiation between traditional and modern practices in small-scale fisheries? How have the historical practices and events shaped current small-scale coastal communities, and can this knowledge benefit current management strategies. The answers will help us understand how coastal economies responded to unprecedented societal and environmental changes by adapting their subsistence practices, technology and culture, while contributing to the foundation of coastal societies in Latin America.
Projet ERC : TRADITION (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of York — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 422314.5 €

TRADITION aims to understand the long-term trajectory of human interaction with coastal resources and its legacy to present day small-scale fisheries in Latin America. Founded on traditional knowledge rooted in the past, small-scale fisheries are a crucial source of food and livelihood for millions of people worldwide, and play a pivotal role in poverty eradication in developing countries. A thorough recognition of the cultural and socio-economic significance of Latin American fisheries requires a temporal component that only archaeology and history can provide. TRADITION will investigate a 4000-year record of coastal exploitation in one of the world's most threatened tropical environments: the Atlantic forest of Brazil. We will draw together archaeological, palaeoecological, historical and ethnographic records to address fundamental questions that impinge upon our current understanding of the development of small-scale fisheries in this region. How did coastal economies adapt to the spread of agriculture? What was the impact of past climate and environmental changes on coastal populations? What was the impact of European colonisation of the Americas on the development of small-scale fisheries? What was the role of historical institutions and regulations in the negotiation between traditional and modern practices in small-scale fisheries? How have the historical practices and events shaped current small-scale coastal communities, and can this knowledge benefit current management strategies. The answers will help us understand how coastal economies responded to unprecedented societal and environmental changes by adapting their subsistence practices, technology and culture, while contributing to the foundation of coastal societies in Latin America.
Projet ERC : Transopera (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Leipzig University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499998.0 €

TRANSOPERA investigates the politics of opera in the Habsburg Empire between the Congress of ‘Transopera’ investigates the politics of opera in the Habsburg Empire between the Congress of Vienna and the outbreak of World War One. With its emphasis on transnational exchanges between the Empire’s different parts and on Austria’s multinational concept of state, my project challenges traditional narratives that have tended to highlight the role of opera as a tool of political nationalism. Instead, the Empire supported opera (the form and the repertoire) as a means to create cultural and intellectual connections between its different peoples, as well as between its political centre and its many peripheries. Following a cross-disciplinary agenda, my project responds to two distinct fields of scholarship so as to establish a new paradigm in our understanding of nineteenth-century opera: the contextual analysis of opera production and its reception; and new trends in Habsburg history, which have moved away from a narrow focus on ethnic and linguistic conflict to examine the role of national hybridity, of dynastic loyalty, and of social structures such as religion, class or gender that cut across national boundaries. ‘Transopera’ connects these two fields of scholarship through a shared challenge to methodological nationalism. It combines cultural and intellectual history to investigate five areas of opera production that deeply marked the monarchy's social, political and cultural life: the role of Italian opera in uniting the Empire culturally across its different crownlands and nationalities; the use of national vernaculars in opera production across the Empire; the function of opera in the context of dynastic representation; the role of grand opéra in staging historical narratives that connected the monarchy to events elsewhere in Europe; and finally, a focus on opera in the Empire’s Southern and Eastern peripheries, as a way of building bridges with its political centre.

Mots-clés : opera,habsburg empire,theatre,europe,nationalism,transnational history