Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : WePredict (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Bern — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1555650.0 €

Microbiota dysbiosis is associated with chronic inflammatory diseases such as allergy, inflammatory bowel diseases, cancer and metabolism-related disorders. It has been reported that exposure to microbial and dietary components early in life may program the immune system to develop tolerance or susceptibility to chronic inflammatory diseases with age. We have recently shown that vigorous immune response induced by gut microbiota at weaning, prevents the development and exacerbation of chronic inflammatory diseases in adult mice. Such immune response is termed the “weaning reaction”. Antibiotic exposure and/or excessive fats intake during this critical window dysregulate the weaning reaction and increase the subsequent susceptibility to develop immunopathology. However, our current knowledge of the biological processes underlying the weaning reaction remains largely unknown. Here we aim to determine the biological processes of the weaning reaction and define the microbial and nutritional signatures at weaning that predict the susceptibility to adult pathology. These aims will be assessed using high-throughput sequencing, machine-learning algorithms and axenic and gnotobiotic mice models. Our project will help deciphering how nutrition and microbiota at weaning orchestrate the immune system development and impact adult chronic inflammatory pathologies susceptibility.

Mots-clés : microbiota,intestine,early life,inflammatory bowel diseases,obesity,predict,immune memory,tolerance,susceptibility,b cells,regulatory t cells,epigenetic
Projet ERC : MicroCONtACT (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Hungarian Academy of Sciences — Pays : Hongrie — Rôle : PI
Acronyme de l'entité : MTA
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Microglia are the main immune cells of the brain, but their role in brain injury is highly controversial due to the difficulties in selectively manipulating and imaging microglial actions in real time. Specifically, it is unclear whether microglia control neuronal survival after injury via shaping the activity of complex neuronal networks in vivo. To this end, we have combined fast in vivo two-photon imaging of neuronal calcium responses with selective microglial manipulation for the first time. Our data suggest that microglia constantly monitor and control neuronal network activity and these actions are essential to limit excitotoxicity and neuronal death after acute brain injury. We also identify microglia as key regulators of spreading depolarization in vivo. However, the underlying mechanisms remained unexplored. Here, I propose that microglia control neuronal excitability and based on preliminary data I set out to investigate how this occurs. We will combine selective, CSF1R-mediated microglia depletion with advanced neurophysiological methods such as in vivo calcium imaging and intracranial EEG for the first time, to reveal how microglia shape activity of complex neuronal networks in the healthy and the injured brain. Then, we will study microglia-neuron interactions from the network level to nanoscale level using in vivo two-photon imaging and super-resolution microscopy. We will apply novel chemogenic and optogenetic approaches to manipulate microglia in real time, assess their role in neuronal activity changes and investigate the molecular mechanisms in vitro and in vivo. Our unpublished data also suggest that inflammation – a key contributor to brain diseases – could disrupt microglia-neuron signaling and we set out to investigate the underlying mechanisms. By using state-of the-art research tools that had not been applied previously in this context, our studies are likely to reveal novel pathophysiological mechanisms relevant for common brain diseases.

Mots-clés : microglia,microglia neuron interactions,brain injury,inflammation,excitotoxicity,spreading depolarization
Projet ERC : MicroSynCom (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : German Center for Neurodegenerative Diseases — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DZNE
Type d'entité : Recherche
Financement ERC de l'entité : 1687476.0 €

Microglia are the resident tissue macrophages of the brain and represent cells of the innate immune system. Looking at microglia from the immunological perspective, much is known about their role during inflammatory processes, factors that activate them and how they response e.g by releasing cytokines to mount an inflammatory response. This response has been shown to be detrimental during disease processes and lead to pruning/loss of synapses, a task microglia carry out also during development. Although microglia obviously play an important role in synaptic pruning and loss, it remains an open question, whether microglia are involved in the process of synapse formation under physiologic conditions. Therefore, the main hypothesis of MicroSynCom is that microglia represent the mediator of synapse formation or linker between pre- and post-synapse: sensing neurotransmitter release at highly active pre-synaptic sites and actively orchestrating the formation of new spines from the dendrite. I propose to investigate and reveal the underlying mechanisms of this tripartite microglia synapse communication process. Therefore, we will use two-photon stimulated emission depletion microscopy (2P-STED), novel viral and genetically encoded sensors for neurotransmitters, as well as optogenetic and chemogenetic manipulation tools. These methods will be combined with behavior test in freely moving, but also head-fixed mice to visualize microglia mediated synapse formation in awake mice. This will allow us for the first time to visualize, investigate and reveal the mechanisms establishing this novel role of microglia as the mediator of synapse formation in life animals and relate it to physiologically relevant neuronal network rewiring.

Mots-clés : microglia,synapse formation,dendritic spine,rewiring,two photon,in vivo imaging,learning and memory
Projet ERC : PolTube (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Umeå University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Microsporidia are opportunistic fungal pathogens that infect organisms as evolutionarily divergent as protists and mammals. Due to their growing impact on the global food supply chain, the environment, and human health, these unusual spore-forming organisms have been classified as emerging pathogens of high priority. Intriguing cell biological features that are central to microsporidian infectivity and pose challenges to drug development are poorly understood due to a lack of structural information and the absence of genetic tools. As energy parasites, microsporidia survive with the smallest eukaryotic genome and without classical mitochondria through an obligate intracellular lifestyle. A fascinating infection mechanism, which involves a long, hollow protein structure, is essential for efficient host invasion. The microsporidia-specific infection apparatus consists of several structural proteins that form the polar tube, which is used to inject the entire cytoplasm from the infectious spore into the host cell. Here, we will use an innovative approach to provide the structural and mechanistic basis of the microsporidian infection mechanism by using cutting-edge structural biology techniques and novel developed in-vivo tools. By studying the endogenous polar-tube, we will identify new elements and provide an architectural model of the invasion organelle. Reconstitution and biochemical characterization of the major components of the polar tube, followed by high-resolution cryo-EM studies, will unravel the polar tube protein interaction network and provide near-atomic information to complement the architectural model. Together with the development of genetic methods to tag, visualize and manipulate components in-vivo, we will provide a comprehensive model of the infection process, give insights into the specialization and evolution of a fascinating and understudied organism and deliver ground-breaking tools to open new frontiers in microsporidian research.

Mots-clés : microsporidia,polar tube,cryo em
Projet ERC : ComplexSwimmers (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Gothenburg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497500.0 €

Microswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing. However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale. This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers. To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications.

Mots-clés : microswimmers,active brownian motion,far from equilibrium physics
Projet ERC : DRAIOCHT (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : National University of Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 130310.0 €

Microwave ablation produces a small and highly controllable heating zone, ideal for the thermal treatment of a range of medical conditions where damage to adjacent structures is a significant risk. Potential applications range from the treatment of small soft-tissue cancers to the management of various venous disorders. The DRAIOCHT project will involve the design, development and pre-clinical evaluation of a novel microwave ablation device for the treatment of disorders of the venous system. The proposed device will provide a new low cost therapeutic medical device, that places greater value on the protection of crucial functional tissue and nerves compared to current ablation devices on the market. The project is of significant economic and societal benefits due to the high prevalence of venous diseases in Europe.

Mots-clés : microwave ablation,varicose veins,venus disease,electrical stimulation,medical devices
Projet ERC : Natural BionicS (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Medical University of Vienna — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3193976.0 €

Missing a limb leads to dramatic impairments in the capacity to move and interact with the environment and to a substantial worsening in quality of life. This deficiency is also associated with a large portion of the sensory-motor cortex facing neural deafness. Missing or damaged limbs can in principle be substituted by robotic limbs, connected to humans with neural interfacing. Despite massive research efforts, however, the bionic reconstruction of limbs currently faces important translational challenges. We aim at filling this gap between academic research and clinical impact with a patient-centric approach that synergistically combines breakthroughs in surgery (Aszmann), neural interfacing (Farina), and robotics (Bicchi). We propose to surgically create bio-connectors (compacted in a bio-hub) to access the spinal cord circuitries by using biological pathways of encoding and decoding neural information. Neural interfacing with the bio-hub will determine an input/output information flow with the spinal cord by decoding the activity of spinal neural cells (output) and stimulating transplanted biological afferent organs (input). The sensory-motor image of the missing limb emerging from this interfacing will be projected in soft robotic arms/legs that will embed kinematic synergies and tactile-proprioceptive functions, intimately matched with the neural sensory-motor synergies extracted from the bio-hub. In this way, Natural BionicS aims at creating a fully integrated, symbiotic replacement of human limbs with robotic parts that the user will feel and command as part of the body. This aim will be achieved with clinical translation aided by the establishment of a Bionic Clinical Board of the three PIs. Here the options of bionic reconstruction will be explored for each patient on a bi-monthly basis, the engineering solutions will be adapted to the clinical challenges, and patients will be identified who best profit from the radical new developments of Natural BionicS.

Mots-clés : prosthetics,neural interfacing,rehabilitation engineering,reconstructive surgery,bionic medicine,soft robotics,sensory motor integration
Projet ERC : Natural BionicS (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3508170.0 €

Missing a limb leads to dramatic impairments in the capacity to move and interact with the environment and to a substantial worsening in quality of life. This deficiency is also associated with a large portion of the sensory-motor cortex facing neural deafness. Missing or damaged limbs can in principle be substituted by robotic limbs, connected to humans with neural interfacing. Despite massive research efforts, however, the bionic reconstruction of limbs currently faces important translational challenges. We aim at filling this gap between academic research and clinical impact with a patient-centric approach that synergistically combines breakthroughs in surgery (Aszmann), neural interfacing (Farina), and robotics (Bicchi). We propose to surgically create bio-connectors (compacted in a bio-hub) to access the spinal cord circuitries by using biological pathways of encoding and decoding neural information. Neural interfacing with the bio-hub will determine an input/output information flow with the spinal cord by decoding the activity of spinal neural cells (output) and stimulating transplanted biological afferent organs (input). The sensory-motor image of the missing limb emerging from this interfacing will be projected in soft robotic arms/legs that will embed kinematic synergies and tactile-proprioceptive functions, intimately matched with the neural sensory-motor synergies extracted from the bio-hub. In this way, Natural BionicS aims at creating a fully integrated, symbiotic replacement of human limbs with robotic parts that the user will feel and command as part of the body. This aim will be achieved with clinical translation aided by the establishment of a Bionic Clinical Board of the three PIs. Here the options of bionic reconstruction will be explored for each patient on a bi-monthly basis, the engineering solutions will be adapted to the clinical challenges, and patients will be identified who best profit from the radical new developments of Natural BionicS.

Mots-clés : prosthetics,neural interfacing,rehabilitation engineering,reconstructive surgery,bionic medicine,soft robotics,sensory motor integration
Projet ERC : DELMIT (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Gothenburg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999985.0 €

Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that encode for 13 of the about 90 proteins present in the respiratory chain. All proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA-encoded genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance is an important cause of neurodegeneration and muscle diseases. The common result of these defects is either mtDNA depletion or accumulation of multiple deletions of mtDNA in postmitotic tissues. The long-term goal (or vision) of research in my laboratory is to understand in molecular detail how mtDNA is replicated and how this process is regulated in mammalian cells. To this end we use a protein biochemistry approach, which we combine with in vivo verification in cell lines. My group was in 2004 the first to reconstitute mtDNA replication in vitro and we have continued to develop even more elaborate system ever since. In the current application, the major focus is studies of the mitochondrial D-loop region, a triple-stranded structure in the mitochondrial genome. The D-loop functions as a regulatory hub and we will determine how initiation and termination of mtDNA replication is controlled from this region. We will also determine the physical organization of the mtDNA replication machinery at the replication fork and establish how mtDNA deletions, a classical hallmark of human ageing, are formed.

Mots-clés : dna polymerase,helicase,primase,ageing and mitochondria
Projet ERC : NEUROMITO (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1500000.0 €

Mitochondria generate most of the energy cells require to function. Deficits in the mitochondrial energy-generating machinery affect 1:5,000 children and cause progressive, debilitating, and usually fatal pathologies collectively known as primary mitochondrial disease. To date, there is no cure for mitochondrial disease and existing treatments are highly ineffective and mostly palliative. High-energy-requiring cells, such as neurons, are especially affected in mitochondrial disease. However, not all neuronal populations are equally affected. Furthermore, the molecular determinants of neuronal vulnerability to mitochondrial disease have not been adequately elucidated, representing a challenge for the development of efficient treatments for these pathologies. To improve on current knowledge on mitochondrial disease and to provide better therapeutic targets, this project focuses on developing ground-breaking mouse genetics and molecular biology tools that will allow the identification and dissection of the molecular determinants of neuronal vulnerability in mitochondrial disease with unprecedented definition. We will develop novel techniques to isolate both the mitochondrial and cytosolic translatome by using ribosomal tagging in vivo as well as to assess intact mitochondrial function with cell-type specificity and temporal resolution. These novel approaches will have a high impact in mitochondrial disease, with the overall aim of identifying novel therapeutic targets that will lead to effective treatments for mitochondrial disease. Furthermore, the high applicability of the tools generated will allow significant breakthroughs in the research of other pathologies with mitochondrial affectation such as diabetes or neurodegenerative processes.

Mots-clés : mitochondrial disease,encephalopathy,cell specific,in vivo,mouse genetics
Projet ERC : RevMito (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Koç University — Pays : Turquie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 463519.07 €

Mitochondrial DNA (mtDNA) encodes several proteins playing key roles in bioenergetics. Pathological mutations of mtDNA can be inherited or may accumulate following treatment for viral infections or cancer. Furthermore, many organisms, including humans, accumulate significant mtDNA damage during their lifespan, and it is therefore possible that mtDNA mutations can promote the aging process. There are no effective treatments for most diseases caused by mtDNA mutation. An understanding of the cellular consequences of mtDNA damage is clearly imperative. Toward this goal, we use the budding yeast Saccharomyces cerevisiae as a cellular model of mitochondrial dysfunction. Genetic manipulation and biochemical study of this organism is easily achieved, and many proteins and processes important for mitochondrial biogenesis were first uncovered and best characterized using this experimental system. Importantly, current evidence suggests that processes required for survival of cells lacking a mitochondrial genome are widely conserved between yeast and other organisms, making likely the application of our findings to human health. We will study the repercussions of mtDNA damage by three different strategies. First, we will investigate the link between a conserved, nutrient-sensitive signalling pathway and the outcome of mtDNA loss, since much recent evidence points to modulation of such pathways as a potential approach to increase the fitness of cells with mtDNA damage. Second, we will explore the possibility that defects in cytosolic proteostasis are precipitated by mtDNA mutation. Third, we will apply the knowledge and concepts gained in S. cerevisiae to both candidate-based and unbiased searches for genes that determine the aftermath of severe mtDNA damage in human cells. Beyond the mechanistic knowledge of mitochondrial dysfunction that will emerge from this project, we expect to identify new avenues toward the treatment of mitochondrial disease.

Mots-clés : yeast,mitochondrial dna,mitochondrial disease,proteostasis,molecular genetics,model organisms,unbiased screens and selections