Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ODE (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Universitätsklinikum Erlangen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2008062.0 €

Osteocytes are long-lived cells within the bone matrix that have a variety of functions in the control of bone remodeling. They are the most frequent cells of the bone by far and mediate the regulation of the mechanical loading-induced bone renewal at the systemic level. Little is known how osteocytes die and how this process affects local bone homeostasis. Nonetheless several local bone diseases such as fracture, osteonecrosis and arthritis are characterized by enhanced osteocyte death and local bone resorption. My preliminary data show that osteocytes, when dying, undergo secondary necrosis, due to their secluded localization within the bone and the absence of phagocyting cells. Hence substantial amounts of damage-associated molecular patterns (DAMPs) are released into the bone micro-environment. I can show that DAMPs effectively osteoclast differentiation via binding to the C-type lectin receptor Mincle. My proposal ODE aims to characterize osteocyte death, the nature of the released DAMPs and the molecular link between osteocyte death and stimulation of osteoclasts. I specifically aim to delineate, in which way osteocytes die within the bone matrix (apoptosis, necrosis, necroptosis, ferroptosis or pyroptosis) and which specific DAMPs are released into the bone marrow via the canalicular network. In this context, local bone diseases such as fracture, osteonecrosis and arthritis will be investigated. In aim 1, I will molecularly characterize osteocyte cell death and block the corresponding death pathways. In aim 2, I will determine putative molecular mechanisms driving osteoclast maturation through the pathways triggered by myeloid specific C-type lectin receptors. In aim 3, I will test the molecular mechanisms of osteocyte death-induced osteoclastogenesis. Overall, my proposal will gain new insights into local bone homeostasis, i.e. the molecular regulation of osteocyte death and the molecular links to an altered local bone microenvironment.

Mots-clés : osteocytes,damps,c type lectin,osteoclasts,bone diseases
Projet ERC : DREAM (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Our ability to communicate using language in conversation is considered the hallmark of human intelligence. Yet, while holding a dialogue is effortless for most of us, modelling this basic human skill by computational means has proven extremely difficult. In DREAM, I address this challenge by establishing a new computational model of a dialogue agent that can learn to take part in conversation directly from data about language use. DREAM stands at the crossroads of the symbolic and the sub-symbolic traditions regarding the nature of human cognitive processing and, by extension, its computational modelling. My model is grounded in linguistic theories of dialogue, rooted in the symbolic tradition, but exploits recent advances in computational learning that allow the agent to learn the representations that it manipulates, which are distributed and sub-symbolic, directly from experience. This is an original approach that constitutes a paradigm shift in dialogue modelling --- from predefined symbolic representations to automatic representation learning --- that will break new scientific ground in Computational Linguistics, Linguistics, and Artificial Intelligence. The DREAM agent will be implemented as an artificial neural network system and trained with task-oriented conversations where the participants have a well-defined end goal. The agent will be able to integrate linguistic and perceptual information and will be endowed with the capability to dynamically track both speaker commitments and partner-specific conventions, leading to more human-like and effective communication. Besides providing a breakthrough in our capacity to build sophisticated conversational agents, DREAM will have substantial impact on our scientific understanding of human language use, thanks to its emphasis on theory-driven hypotheses and model analysis.

Mots-clés : dialogue modelling,computational semantics and pragmatics
Projet ERC : SPIN (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Pennsylvania — Pays : Etats-Unis — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 69805.0 €

Our ability to remember past events and experiences lies at the core of cognition and behaviour. But how do fleeting moments get converted into durable memory traces? Recent work has highlighted the pivotal role of post-learning sleep for successful memory consolidation, the process of stabilising new memories over time. However, little is known about the neurophysiological mechanisms through which the sleeping brain consolidates new memories. Not only has this left a gap in our understanding of memory formation as a whole, but also the means to modulate memories during sleep have remained underexplored. SPIN will test the exciting hypothesis that particular electrophysiological signatures of sleep, namely sleep spindles, are the mechanistic vehicle driving memory consolidation. Specifically, I hypothesise that in coordination with hippocampal reactivation events, sleep spindles are deployed to cortical learning sites where they induce lasting structural changes. Using intracranial recordings from the human hippocampus (measuring single neuron firing and associated ‘ripple’ oscillations) and from an array of cortical areas, we will first establish whether spindles are temporally aligned with hippocampal reactivation events. Next, we will use high-density scalp EEG and functional as well as structural MRI in healthy participants to test whether spindle deployment to cortical learning sites predicts structural changes in these regions. To assert causality, we will examine the effects of invasive spindle perturbation in patients on memory consolidation. Finally, we will experimentally enhance local spindles to harness their potential as a tool for boosting human memory. In sum, SPIN will use an unprecedented array of human brain recording and stimulation techniques to provide a mechanistic link between learning, sleep and structural brain changes, culminating in novel tools to enhance human learning and memory.

Mots-clés : memory,sleep,consolidation,brain imaging,brain stimulation
Projet ERC : CIL2015 (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1993802.59 €

Our aim is to dissect the mechanisms of contact inhibition of locomotion (CIL), a process whereby migrating cells collide and repel each other, as it is now clear that CIL is pivotal to understanding embryogenesis and pathologies such as cancer. We have developed an in vivo model using Drosophila macrophages (hemocytes), along with novel analytical tools, to examine the contact inhibition response in cells during development. We therefore have an unprecedented opportunity to address CIL in a genetically tractable organism within a physiologically relevant setting. This model has revealed that a precisely controlled CIL response is a significant driving force behind the acquisition of embryonic patterns, and recent data show that this precision requires a series of synchronized changes in cytoskeletal dynamics. Our central hypothesis is that key to this cellular ‘dance’ is mechanosensation of the collision, which integrates subsequent signaling mechanisms to choreograph the steps of the contact inhibition process. The first part of this proposal will elucidate the molecular mechanisms controlling CIL by exploiting our unique ability to live image and genetically dissect this process in Drosophila. We will also take an interdisciplinary approach to elucidate the mechanical aspects of the response, which will allow us to examine the feedback between signaling pathways and the physical forces of the CIL response. We will subsequently extend our detailed understanding of the CIL process, and our novel set of analytical tools, to mammalian cell types and model systems. This will allow us to develop new assays to directly probe the mechanics of CIL and begin to investigate the function of this underexplored process in other cell types. This in depth knowledge of the response places us in the best position to extend our understanding of CIL to new physiologically relevant scenarios that in the future will impact on human health.
Projet ERC : SINDAM (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Durham University — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 809766.27 €

Our atmosphere appears to be a reservoir of inert gaseous molecules, while in reality, it is also composed of a plethora of highly reactive molecules and radicals. Among these are the volatile organic compounds (VOCs) that contribute substantially to both global warming and air pollution. Detailed atmospheric models attempt to describe the incredibly complex network of chemical reactions resulting from VOC oxidation in our troposphere and to predict its composition, paramount for informing societal and political decisions and regulations. A surprising observation, though, is that the role of sunlight in the reactions of VOC intermediates is scarcely understood, even though excited-state dynamics, triggered by sunlight absorption, initiate most of the atmosphere’s chemistry. This lack of information is partly due to the challenge in conducting photochemical experiments on transient VOC species. As a result, VOC-related chemical mechanisms are mostly based on a ground electronic state chemistry, leading to some critical deviations between the predicted and observed composition of the atmosphere. Also, vastly neglecting the rich photochemistry of these VOC species leads to a poorer understanding of their resulting environmental impact. This project, SINDAM, launches the field of in silico atmospheric photochemistry by using recent breakthroughs in theoretical and computational chemistry to establish the importance of photochemical processes of VOCs in the atmosphere, either in isolation or in contact with water molecules. SINDAM will answer the simple yet critical question: how ubiquitous are photophysical and photochemical effects in the atmospheric chemistry of VOCs? Hence, this project will stimulate an exciting new synergistic area at the edge between theoretical and atmospheric chemistry, leading to a real, societal impact by improving the predictive power of atmospheric models in the context of global warming and air quality.
Projet ERC : SINDAM (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 689690.73 €

Our atmosphere appears to be a reservoir of inert gaseous molecules, while in reality, it is also composed of a plethora of highly reactive molecules and radicals. Among these are the volatile organic compounds (VOCs) that contribute substantially to both global warming and air pollution. Detailed atmospheric models attempt to describe the incredibly complex network of chemical reactions resulting from VOC oxidation in our troposphere and to predict its composition, paramount for informing societal and political decisions and regulations. A surprising observation, though, is that the role of sunlight in the reactions of VOC intermediates is scarcely understood, even though excited-state dynamics, triggered by sunlight absorption, initiate most of the atmosphere’s chemistry. This lack of information is partly due to the challenge in conducting photochemical experiments on transient VOC species. As a result, VOC-related chemical mechanisms are mostly based on a ground electronic state chemistry, leading to some critical deviations between the predicted and observed composition of the atmosphere. Also, vastly neglecting the rich photochemistry of these VOC species leads to a poorer understanding of their resulting environmental impact. This project, SINDAM, launches the field of in silico atmospheric photochemistry by using recent breakthroughs in theoretical and computational chemistry to establish the importance of photochemical processes of VOCs in the atmosphere, either in isolation or in contact with water molecules. SINDAM will answer the simple yet critical question: how ubiquitous are photophysical and photochemical effects in the atmospheric chemistry of VOCs? Hence, this project will stimulate an exciting new synergistic area at the edge between theoretical and atmospheric chemistry, leading to a real, societal impact by improving the predictive power of atmospheric models in the context of global warming and air quality.
Projet ERC : EditMHC (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Goethe University Frankfurt — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2181250.0 €

Our body constantly encounters pathogens or malignant transformation. Consequently, the adaptive immune system is in place to eliminate infected or cancerous cells. Specific immune reactions are triggered by selected peptide epitopes presented on major histocompatibility complex class I (MHC-I) molecules, which are scanned by cytotoxic T lymphocytes. Intracellular transport, loading, and editing of antigenic peptides onto MHC-I are coordinated by a highly dynamic multisubunit peptide-loading complex (PLC) in the ER membrane. This multitasking machinery orchestrates the translocation of proteasomal degradation products into the ER as well as the loading and proofreading of MHC-I molecules. Sampling of myriads of different peptide/MHC-I allomorphs requires a precisely coordinated quality control network in a single macromolecular assembly, including the transporter associated with antigen processing TAP1/2, the MHC-I heterodimer, the oxidoreductase ERp57, and the ER chaperones tapasin and calreticulin. Proofreading by MHC-I editing complexes guarantees that only very stable peptide/MHC-I complexes are released to the cell surface. This proposal aims to gain a holistic understanding of the PLC and MHC-I proofreading complexes, which are essential for cellular immunity. We strive to elucidate the mechanistic basis of the antigen translocation complex TAP as well as the MHC-I chaperone complexes within the PLC. This high-risk/high-gain project will define the inner working of the PLC, which constitutes the central machinery of immune surveillance in health and diseases. The results will provide detailed insights into the architecture and dynamics of the PLC and will ultimately pave the way for unraveling general principles of intracellular membrane-embedded multiprotein assemblies in the human body. Furthermore, we will deliver a detailed understanding of mechanisms at work in viral immune evasion.

Mots-clés : membrane proteins,macromolecular complexes,er quality control,membrane transporters,fluorescence labeling,chemical biology,super resolution microscopy
Projet ERC : GEOSTICK (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Hull — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2581155.0 €

Our coasts, estuaries, & low-land river environments are some of the most sensitive systems to sea-level rise & environmental change. In order to manage these systems, & adapt to future changes, we desperately need to be able to predict how they will alter under various scenarios. However, our models for these environments are not yet robust enough to predict, with confidence, very far into the future. Moreover, we also need to improve how we use our understanding of modern environments in reconstructing paleo-environments, where significant assumptions have been made in the way in which relationships derived from the modern have been applied to ancient rocks. One of the main reasons our models, & geological interpretations, of these environments, are not yet good enough is because these models have formulations that are based on assumptions that these systems are composed of only non-cohesive sands. However, mud is the most common sediment on Earth & many of these systems are actually dominated by biologically-active muds & complex sediment mixtures. We need to therefore find ways to incorporate the effect of sticky mud & sticky biological components into our predictions. Recent work my colleagues & I have published show just how important such abiotic-biotic interactions can be: inclusion of only relatively small (<0.1% by mass) quantities of biological material into sediment mixtures can reduce alluvial bedform size by an order of magnitude. However, this is just a start & there is much to do in order to advance our fundamental understanding & develop robust models that predict the combined effects of abiotic & biotic processes on morphological evolution of these environments under changing drivers & conditions. GEOSTICK will deliver this advance allowing us to test how sensitive these environments are, assess if there are tipping points in their resilience & examine evidence for the evolution of life in the ancient sediments of early Earth and Mars.

Mots-clés : sediment transport,delta environments,climate change,planetary science,morphodynamics,geomorphology,sustainability,climate adaptation
Projet ERC : nextDART (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Technical University of Denmark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : DTU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499070.0 €

Our current ability to map T-cell reactivity to certain molecular patterns poorly matches the huge diversity of T-cell recognition in humans. Our immune system holds approximately 107 different T-cell populations patrolling our body to fight intruding pathogens. Current state-of-the-art T-cell detection enables the detection of 45 different T-cell specificities in a given sample. Therefore comprehensive analysis of T-cell recognition against intruding pathogens, auto-immune attacked tissues or cancer is virtually impossible. To gain insight into immune recognition and allow careful target selection for disease intervention, also on a personalized basis, we need technologies that allow detection of vast numbers of different T-cell specificities with high sensitivity in small biological samples. I propose here a new technology based on multimerised peptide-major histocompatibility complex I (MHC I) reagents that allow detection of >1000 different T-cell specificities with high sensitivity in small biological samples. I will use this new technology to gain insight into the T-cell recognition of cancer cells and specifically assess the impact of mutation-derived neo-epitopes on T cell-mediated cancer cell recognition. A major advantage of this new technology relates to the ability of coupling the antigen specificity to the T-cell receptor sequence. This will enable us to retrieve information about T-cell receptor sequences coupled with their molecular recognition pattern, and develop a predictor of binding between T-cell receptors and specific epitopes. It will ultimately enable us to predict immune recognition based on T-cell receptor sequences, and has the potential to truly transform our understanding of T cell immunology. Advances in our understanding of T cell immunology are leading to massive advances in the treatment of cancer. The technologies I propose to develop and validate will greatly aid this process and have application for all immune related diseases.

Mots-clés : t cell detection,mhc multimers,multiplex,technology development,cancer,mutation derived antigens,neo epitope mapping,tcr sequencing,prediction algorithms
Projet ERC : NEUROGOAL (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 : 1499933.0 €

Our daily life is a complex chain of decisions and actions that shapes our behaviors. Individuals tend to choose the best action possible among different alternatives through “goal-directed” decision-making. Given that action-selection is supposed to occur on the basis of the individual subjective evaluation of the relative costs and benefits of each action, two types of information need to be integrated within choice-specific neuronal representations: the causal consequences of an action (outcome) and the value of the outcome. The prefrontal cortex (PFC) appears to be well suited to organize such action-selection. However, despite the growing interest in decision-making over the past few years, the neuronal and synaptic mechanisms underlying goal-directed action-selection in normal and pathological conditions remain elusive. By using two-photon imaging over long-time frames in behaving mice, our project will first determine how alternative choices are encoded by specific neuronal representations in the PFC, and how they are compared during decision-making to select to best action possible. To achieve flexible behaviors in a dynamic environment, individuals must rapidly update these representations according to the difference between the predicted and the obtained outcome. Many cortical and subcortical structures act in coordination to encode and process changes in the outcome value, but the synaptic underpinnings remain unknown. Our proposal will take full advantage of in vivo methods combining electrophysiology, optogenetic and genetically-encoded calcium indicators to address the causal relationship between subcortical population dynamics and prefrontal neuronal processing during decision-making and behavioral flexibility. Finally, given that motivational alterations are observed in many human neuropsychiatric disorders including autism, we will tackle synaptic, cellular and behavioral decision-making deficits in a mouse model of autism.

Mots-clés : decision making,synaptic plasticity,prefrontal cortex,amygdala,dopamine,in vivo,cranial window,head restrained mice,in vivo two photon imaging,optogenetics,calcium imaging,patch clamp