Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CancerFluxome (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1481250.0 €

The metabolism of cancer cells is altered to meet cellular requirements for growth, providing novel means to selectively target tumorigenesis. While extensively studied, our current view of cancer cellular metabolism is fundamentally limited by lack of information on variability in metabolic activity between distinct subcellular compartments and cells. We propose to develop a spatio-temporal fluxomics approach for quantifying metabolic fluxes in the cytoplasm vs. mitochondria as well as their cell-cycle dynamics, combining mass-spectrometry based isotope tracing with cell synchronization, rapid cellular fractionation, and computational metabolic network modelling. Spatio-temporal fluxomics will be used to revisit and challenge our current understanding of central metabolism and its induced adaptation to oncogenic events – an important endeavour considering that mitochondrial bioenergetics and biosynthesis are required for tumorigenesis and accumulating evidences for metabolic alterations throughout the cell-cycle. Our preliminary results show intriguing oscillations between oxidative and reductive TCA cycle flux throughout the cell-cycle. We will explore the extent to which cells adapt their metabolism to fulfil the changing energetic and anabolic demands throughout the cell-cycle, how metabolic oscillations are regulated, and their benefit to cells in terms of thermodynamic efficiency. Spatial flux analysis will be instrumental for investigating glutaminolysis - a ‘hallmark’ metabolic adaptation in cancer involving shuttling of metabolic intermediates and cofactors between mitochondria and cytoplasm. On a clinical front, our spatio-temporal fluxomics analysis will enable to disentangle oncogene-induced flux alterations, having an important tumorigenic role, from artefacts originating from population averaging. A comprehensive view of how cells adapt their metabolism due to oncogenic mutations will reveal novel targets for anti-cancer drugs.

Mots-clés : computational biology,bioinformatics,isotope tracing,cancer metabolism,metabolic flux analysis  mfa,constraint based modeling  cbm
Projet ERC : SERENiTi (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : Ghent University — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The microKinetic Engine (μKE), an existing user-friendly software for steady-state simulation purposes which is ready for commercialization, will find a totally new application area by incorporating the ability to account for important transient occurrences commonly encountered in industry, e.g., startup, shutdown and perturbations of the continuous flow reactor operation. The implementation of a transient solution strategy will also render the software more robust, even for steady-state simulations. It will allow a smoother, more ‘serene’ evolution towards the mathematical solution of the set of equations describing the simulated process/reaction. Regarding reaction kinetics determination, implementing the possibility of transient kinetic data analysis will provide a deeper insight into the underlying reaction mechanism. Catalyst deactivation, as an inevitable transient phenomenon, will be explained and addressed either in a global manner, or even in terms of microkinetics, i.e., elementary reaction steps.

Mots-clés : software,simulation,regression,reaction mechanism,transient phenomena,elementary steps,kinetics
Projet ERC : Homo.symbiosus (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Assistance publique - Hôpitaux de Paris — Pays : France — Rôle : Partner
Acronyme de l'entité : AP-HP
Type d'entité : Recherche
Financement ERC de l'entité : 200000.0 €

The microbiomics revolution has favoured the recognition of the gut as a true organ and the importance of man-microbes symbiosis in health and disease. Derived from a long co-evolution the latter has been challenged by numerous environmental triggers, modern lifestyles, changes in birth modalities, nutritional transition and therapeutic attitudes. A large fraction of the human population has tentatively entered a man-microbes dysbiotic state characterized by altered interactions between microbiome and host features with auto-aggravating crosstalk signals. The result is increased incidence of incurable immune-mediated diseases of modern societies that affect a third the human population on earth today and for which current therapeutics only address symptoms alleviation, rather than considering man as a holobiont. In this context and its resulting threat for the human species, I will carry out a project geared to open a new era of individualized preventive care and novel gut ecology-based therapeutic approaches. The project will assemble insights and contributions from theoretical to experimental ecology, quantitative and functional microbiomics, preclinical work, cohort studies and clinical trials, so as to: • Validate the concept of critical transition and alternative stable state as it applies to a shift from man-microbes symbiosis to disease-prone man-microbes dysbiosis • Assess the potential of diet alone to promote such a shift • Model the symbiosis-to-dysbiosis transitions and derive predictors of tipping points • Propose counter-measures that may allow to break vicious circles and restore a balanced, health-prone, man-microbes symbiosis by concomitantly acting upon microbiome and host features • Validate strategies to reinforce ecological robustness and restore man-microbes symbiosis Based on a paradigm shift, the proposed work will set the grounds for future personalized preventive nutrition and clinical management considering man as a true holobiont.

Mots-clés : intestinal ecology,host microbiota symbiosis,critical transition,dysbiosis,microbiotherapy
Projet ERC : PREDATOR (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Université Catholique de Louvain — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499688.0 €

The model predatory bacterium Bdellovibrio bacteriovorus feeds upon other Gram-negative bacteria, including pathogenic strains. Upon entry inside the periplasmic space of the prey envelope, B. bacteriovorus initiates an exquisite developmental program in which it digests the host resources while ensuring the osmotic stability of its niche. In the periplasm, the predator cell grows as a polyploid filament, before releasing a variable, odd or even number of daughter cells upon a non-binary division event. The progeny is then liberated to hunt for new prey. B. bacteriovorus is now attracting a revived attention as several in vivo models of infection established its promising “living antibiotic” potential. Despite this remarkable lifestyle, the fields of bacterial cell biology and antibiotics research still lack a comprehensive understanding of how this micro-predator thrives inside the envelope of other bacteria. Indeed, the molecular factors behind the non-canonical cell biology of B. bacteriovorus are still largely mysterious. My goal is to tackle this question by unraveling the novel mechanisms that control key processes of the fascinating cell cycle of this bacterium, using a unique combination of quantitative live imaging of predation at the single-cell level, bacterial genetics and molecular biology. Specifically, I aim to (i) uncover how the genetic information is organized, copied and partitioned in a polyploid cell before non-binary division, (i) shed light on factors that polarize the predator cell, and (iii) discover prey envelope features that influence the predation cycle. Because the biology of B. bacteriovorus stands beyond textbook standards, our results will provide mechanistic insight into important biological questions that remained unexplored using “classical” model species. If successful, this project will advance bacterial cell biology, while offering an innovative contribution to the fight against antibiotics-resistant pathogens.

Mots-clés : bacterial cell biology,chromosome replication and segregation,protein subcellular localization,live imaging of bacterial cells,bacterial predation,quantitative fluorescence microscopy
Projet ERC : FIRM (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of London — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 571954.25 €

The molecular communication between mitochondria and nucleus is an integrated bi-directional crosstalk - anterograde (nucleus to mitochondria) and retrograde (mitochondria to nucleus) signalling pathways. The mitochondrial retrograde response (MRR) is driven by defective mitochondrial function, which increases cytosolic reactive oxygen species (ROS) and Ca2+. Metabolic reprogramming is a key feature in highly proliferative cells to meet the energy needs for rapid growth by generating substrates for cellular biogenesis. In these mitochondria retro-communicate with the nucleus to induce wide-ranging cytoprotective effects exploited to develop resistance against treatment and sustain uncontrolled growth. Recently, the mitochondrial management of cholesterol-derived intermediates for the synthesis of steroids has been demonstrated as a determinant in the oncogenic reprogramming of cellular environment. We hypothesise that cholesterol-enriched domains facilitate the communication between remodelled mitochondria and nucleus to expedite MRR. This mechanism may be exploited during abnormal cell growth in which cholesterol metabolism and associated molecules are increased. This application capitalizes on expertise in cell signalling and metabolism to interrogate core pathways and unveil molecular sensors and effectors that define form and function of the MRR by: I. Elucidating the mechanism of metabolic regulation of MRR, describing the role exerted by cholesterol trafficking; II. Unveiling microdomains for mito-nuclear communication established by remodelled, autophagy escaped, mitochondria; III. Validating protocols to modulate and target MRR for diagnostic and therapeutic benefit; The experimental plan will (i) define a molecular signalling axis that currently stands uncharacterized, (ii) provide mechanistic knowledge for preventive, and (iii) therapeutic applications to counteract deficiencies associated with stressed, dysregulated mitochondria.

Mots-clés : mitochondria,inter organelles communication
Projet ERC : QCDforfuture (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1438003.0 €

The momentous discovery of the Higgs boson in 2012 marked the start of a new era in particle physics. The increase in energy of collisions at the Large Hadron Collider (LHC) this year allows us to probe fundamental physics at an energy scale which has been out of reach until now. This presents a challenge to particle theory to keep pace with these developments, and respond to the fact that Standard Model interactions will have different features in this new energy range. We must understand these differences in order to extract as much information as possible from LHC data, and in particular to identify any signs of new physics. My framework, High Energy Jets, is the only tool of its kind to include the dominant high-energy corrections to all orders in the strong coupling and these have already been shown to be necessary to describe data at the lower collisions energies of 7 and 8 TeV. However, these corrections alone are not enough. My proposed research programme will develop a novel and powerful framework for theoretical predictions based on the lessons learned from LHC Run I. In particular it will combine the necessary high-energy corrections with state-of-the-art next-to-leading-order (NLO) fixed-order descriptions. A separate objective is to combine the high-energy corrections with the resummation contained in parton shower programs. This is necessary to describe data in regions where there is both evolution in rapidity and transverse momentum. The ultimate goal is to combine all three: high-energy corrections, NLO calculation and parton shower. Separate theoretical objectives will significantly improve our understanding of the underlying theory, which should ultimately enhance our description of data far beyond any current prediction. This will be the most complete description of quantum chromodynamics at colliders to date, and will be essential for the exploitation of future data from the LHC and beyond.
Projet ERC : FlowMachines (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Sony (United Kingdom) — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 0.0 €

The music industry has seen its profits decrease drastically since 2000, challenged by other forms of entertainment such as video games and the internet, as well as by illegal download and piracy. However, there is a growing activity in the so-called music synchronization business: music composed, retrieved, or otherwise produced to fit with the many constraints of videos, movies, games or commercials. Synchronized music has to satisfy complex constraints, specified temporally (specific events at specific moments, or, in the case of interactive music, specific moods matching the player’s situation, etc.). Major movie, game and advertisement companies devote considerable budgets to get synchronized music by famous artists. Producing such synchronized music is a costly process currently performed manually by well-known artists or specialized studios. This results in prohibitive costs for high-quality synchronized music, that only a few professional customers can afford. The commercial value of synchronized music lies in the style of the composer. Style is what makes an artist’s music easily recognizable: Paul McCartney has a unique composition style, Joao Gilberto has a distinctive guitar accompaniment style, and Take 6 are well known for their incomparable harmonization style. Producing operational representations of style is precisely the subject matter of the ERC project Flow-machines, which already produced scientific and technical breakthroughs: turning style into a new content type is within reach. The next step is to explore commercial strategies to exploit style. The goal of this PoC project is to apply these techniques to synchronized music, and to study three business models in the movie, game and advertisement sectors. The project will: 1) develop a style manipulation prototype for synchronized music, 2) evaluate the prototype in the key industrial sectors and 3) clear legal issues related to the exploitation of style information.

Mots-clés : music industry,content generation,constraints,synchronization,style,games,film industry
Projet ERC : Myelination (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 480304.98 €

The myelin sheath is a plasma membrane extension that is laid down in regular spaced segments along axons of the nervous system. In the central nervous system it is formed by oligodendrocytes that spirally wrap their plasma membrane around axons to generate a highly abundant, tightly packed stack of membranes with unique structural properties. Previously, myelin has been regarded as an inert and purely insulating membrane, but it now appears that myelin is metabolically active, providing metabolic support to the underlying axon and participating in information processing by modulating velocity and synchronicity of nerve impulses in neuronal networks. In addition, myelination is not limited to the period of early post-natal development, but continuous into adulthood where it appears to be regulated by neuronal stimuli. This paradigm shift should be fuelled by new knowledge about myelin biology. Here, we plan to fill this gap by addressing the molecular basis of myelin growth, plasticity and remodelling. We will determine the factors that determine whether and to what extent an axon will be myelinated or not, the forces that drive myelin around the axon, the structural basis of myelin plasticity and the mechanisms of myelin turnover in the adult. We will test the hypothesis that microglia actively participate in myelin turnover by taking up myelin fragments that pinch off from the myelin sheath. To realize these aims we plan to pursue an integrative and multidisciplinary approach by bringing together genetics, biochemistry, proteomics and imaging in various model systems. The innovation arises from the combination of high-resolution imaging with molecular approaches in different cell types to obtain a unifying mechanistic understanding of myelin formation, maintenance and degradation. If successful, the project would not only explain how myelin is generated during brain development, but also give insight into how myelin plasticity could fine-tune neuronal networks.

Mots-clés : myelin,glia,oligodendrocytes,axons,membranes
Projet ERC : TEDE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1061384.59 €

The nature of many of the most energetic explosions in the Universe remains a central unanswered question in contemporary astrophysics. While progress has been made towards the origins of many of the more commonly observed transients – including “normal” core collapse supernovae and long-duration gamma-ray bursts – there remain important mysteries, both new and old. Recent studies suggest that many of the most energetic explosive transients are powered by a central engine that is either an accreting black hole or a highly magnetic neutron star (a magnetar). These engines input energy into the explosion and transform the later emission, as well as having a profound impact on metal yields, feedback into the interstellar medium, remnant evolution, particle acceleration (e.g. high energy cosmic rays) and neutrino production. The creation of the engine may also produce strong gravitational wave transients, which are likely to be discovered (if they have not already been) by the new generation of ground-based interferometers. I propose a detailed study of engine driven transients throughout the Universe, utilizing insights from both the transients themselves and their local and wider environments. In particular, my work will; a) search for evidence of long-lived engines in the longest gamma-ray bursts, and determine the effects these engines have on the appearance of associated supernovae, b) determine the properties of engines in very long gamma-ray transients thought to be tidal disruption flares, and determine if these are indeed tidal flares or unusual supernovae c) map the properties of the engines seen in short-GRBs, allowing us to hone our expectations for d) the identification and study of the first electromagnetic counterparts to GW sources, and their environments. I will achieve this by the creation of an experienced team of postdoctoral fellows and senior staff with a skills-set tuned to address these central questions.

Mots-clés : gamma ray bursts,tidal disruption events,supernovae
Projet ERC : TEDE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of Leicester — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 171243.63 €

The nature of many of the most energetic explosions in the Universe remains a central unanswered question in contemporary astrophysics. While progress has been made towards the origins of many of the more commonly observed transients – including “normal” core collapse supernovae and long-duration gamma-ray bursts – there remain important mysteries, both new and old. Recent studies suggest that many of the most energetic explosive transients are powered by a central engine that is either an accreting black hole or a highly magnetic neutron star (a magnetar). These engines input energy into the explosion and transform the later emission, as well as having a profound impact on metal yields, feedback into the interstellar medium, remnant evolution, particle acceleration (e.g. high energy cosmic rays) and neutrino production. The creation of the engine may also produce strong gravitational wave transients, which are likely to be discovered (if they have not already been) by the new generation of ground-based interferometers. I propose a detailed study of engine driven transients throughout the Universe, utilizing insights from both the transients themselves and their local and wider environments. In particular, my work will; a) search for evidence of long-lived engines in the longest gamma-ray bursts, and determine the effects these engines have on the appearance of associated supernovae, b) determine the properties of engines in very long gamma-ray transients thought to be tidal disruption flares, and determine if these are indeed tidal flares or unusual supernovae c) map the properties of the engines seen in short-GRBs, allowing us to hone our expectations for d) the identification and study of the first electromagnetic counterparts to GW sources, and their environments. I will achieve this by the creation of an experienced team of postdoctoral fellows and senior staff with a skills-set tuned to address these central questions.

Mots-clés : gamma ray bursts,tidal disruption events,supernovae