Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CTO Com (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Institut Mines-Télécom — Pays : France — Rôle : PI
Acronyme de l'entité : IMT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1495287.52 €

Emergence of a large number of distributed decision and control systems (e.g., in health care, transportation, and energy management), combined with increasing demands of traditional communications (e.g., due to multiview videos), create an imminent need for highly improved communication systems. We advocate that—combined with improvements in battery, antenna, and chip technologies—context- and/or task-oriented communication techniques will bring the desired breakthrough. Specifically, context- oriented techniques will greatly improve performance, because future networks have complex infrastructures (with cache-memories, cloud-RANs, etc.) allowing the terminals to collect side-informations about other terminals’ data or signals, and because many distributed decision systems rely on numerous devices with correlated measurements. Task-oriented techniques promise even larger gains, especially in distributed decision systems where decisions take value on a small range, and thus the traditional approach of communicating sequences of observed signals results in a huge overhead. Information theory, and in particular distributed joint source-channel coding, provides a general framework for designing context-oriented communication techniques. Such a general framework is missing for task-oriented communication. Previous results indicate that creative usages of information theory on its frontier to statistics and decision theory are well-suited for designing task-oriented communication techniques for applications as diverse as coordination of smart devices, distributed hypothesis testing, and clustering of data. Our goal is to design context- and/or task-oriented communication techniques for these three applications and for cache-aided communication. Besides the high gains that our new techniques bring directly to these applications, the complementarity of our applications and obtained results will facilitate a future general framework for context- and task-oriented communication.
Projet ERC : PHARMS (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Helmholtz Zentrum München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HMGU
Type d'entité : Recherche
Financement ERC de l'entité : 1499650.0 €

Emergence of antimicrobial resistance (AMR) is a grand scientific challenge of our time that has killed more than 700,000 people worldwide. Phage therapy, a promising complement to antibiotics, utilizes viruses of bacteria (bacteriophages) or phage-derived inhibitors as natural ways to fight AMR. The main obstacles in the clinical application of phage-based AMR therapy are the limited number of phage isolates and the unknown molecular mechanisms of phage-delivered bactericidal action. Building on the recent advances of my group in high-throughput, culture-independent but host-targeted methodologies, PHARMS aims to deploy a revolutionary approach: to screen for all possible phages of a resistant bacterial isolate, characterize multiple lines of their bactericidal functions, and use this information for the design of a whole battery of phage-based therapies that employ multifaceted modes of action. Using an interdisciplinary research plan, PHARMS will discover phage-specific bactericidal action modes at all possible levels ranging from nucleotide sequence and transcription to translation, in order to elucidate the molecular mechanisms driving phage-mediated inhibition of AMR Acinetobacter baumannii, Helicobacter pylori, & Haemophilus influenzae (WP1). These discoveries, together with novel synthetic biology tools, will enable us to engineer an array of phage vectors that mimic phage-deployed bactericidal modes discovered under WP1, including transport of alien genes to deliver bactericidal effects (WP2). PHARMS will provide molecular confirmation and in vitro & in vivo validation of the functions of phage-encoded bactericidal peptides and enzymes (WP3). By elucidating universal and specific mechanisms of phage-delivered inhibition of AMR pathogens, PHARMS is positioned to provide the rational framework for the design of novel therapeutic strategies aimed at treating common and life-threatening infectious diseases.
Projet ERC : MICRONEX (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1446250.0 €

Engineers can actively contribute to fields thought to be out of their “comfort zones”. We can be leaders of discoveries that translate into advances in the understanding of disease and improving human health. Engineers might use different language and tools than Life Sciences Scientists but we find a common ground, as the laws of Thermodynamics, Physics, and Mathematics also apply to biological phenomena. The development of microbioreactors (μBRs) reconstructing biologically sound niches can revolutionize medical research. In our bodies cells reside in a complex milieu, the microenvironment (μEnv), regulating their fate and function. Most of this complexity is lacking in standard laboratory models, leading to readouts poorly predicting the in vivo situation. This is particularly felt in cancer research, as tumors are extremely heterogeneous and capable of conditioning both the local μEnv and distant organs. Neuroblastoma (NB) is the most common and difficult to cure pediatric malignant solid tumor. Secreted exosomes are means by which NBs reshape their μEnv and induce local and long-range changes in cells, regulating progression and prognosis. But the mechanisms involved are yet not completely understood. A major limitation is the difficulty to model in vitro the local in vivo dynamic μEnv. We hypothesize that μBRs exploiting classical engineering principles will solve the limitations of existing classical culture models. We propose to develop platforms and test their edge over classical approaches in decoding the role of exosomes and μEnv in NB. Our μBRs generate time and space-resolved concentration gradients, support fast dynamic changes and reconstruct complex interactions between cells and tissues while performing multifactorial and parallelized experiments. We expect that our technologies will bridge the gap between in vitro techniques and in vivo biological phenomena leading to significant and novel results, shedding light on previously unexplored scenarios.

Mots-clés : micro  system  engineering
Projet ERC : SCORA (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University Hospital Cologne — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 23125.0 €

Enhancers control the correct spatio-temporal activation of gene expression. A comprehensive characterization of the properties and regulatory activities of enhancers as well as their target genes is therefore crucial to understand the regulation and dysregulation of differentiation, homeostasis and cell type specificity. Genome-wide chromatin assays have provided insight into the properties and complex architectures by which enhancers regulate genes, but the understanding of their mechanisms is fragmented and their regulatory targets are mostly unknown. Several factors may confound the inference and interpretation of regulatory enhancer activity. There are likely many kinds of regulatory architectures with distinct levels of output and flexibility. Despite this, most state-of-the-art genome-wide studies only consider a single model. In addition, chromatin-based analysis alone does not provide clear insight into function or activity. This project aims to systematically characterize enhancer architectures and delineate what determines their: (1) restricted spatio-temporal activity; (2) robustness to regulatory genetic variation; and (3) dynamic activities over time. My work has shown enhancer transcription to be the most accurate classifier of enhancer activity to date. This data permits unprecedented modeling of regulatory architectures via enhancer-promoter co-expression linking. Careful computational analysis of such data from appropriate experimental systems has a great potential for distinguishing the different modes of regulation and their functional impact. The outcomes have great potential for providing us with new insights into mechanisms of transcriptional regulation. The results will be particularly relevant to interpretation of regulatory genetic variations. Ultimately, knowing the characteristics and conformations of enhancer architectures will increase our ability to link variation in non-coding DNA to phenotypic outcomes like disease susceptibility.

Mots-clés : transcriptional regulation,enhancers,enhancer rna
Projet ERC : SCORA (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Birmingham — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 103590.0 €

Enhancers control the correct spatio-temporal activation of gene expression. A comprehensive characterization of the properties and regulatory activities of enhancers as well as their target genes is therefore crucial to understand the regulation and dysregulation of differentiation, homeostasis and cell type specificity. Genome-wide chromatin assays have provided insight into the properties and complex architectures by which enhancers regulate genes, but the understanding of their mechanisms is fragmented and their regulatory targets are mostly unknown. Several factors may confound the inference and interpretation of regulatory enhancer activity. There are likely many kinds of regulatory architectures with distinct levels of output and flexibility. Despite this, most state-of-the-art genome-wide studies only consider a single model. In addition, chromatin-based analysis alone does not provide clear insight into function or activity. This project aims to systematically characterize enhancer architectures and delineate what determines their: (1) restricted spatio-temporal activity; (2) robustness to regulatory genetic variation; and (3) dynamic activities over time. My work has shown enhancer transcription to be the most accurate classifier of enhancer activity to date. This data permits unprecedented modeling of regulatory architectures via enhancer-promoter co-expression linking. Careful computational analysis of such data from appropriate experimental systems has a great potential for distinguishing the different modes of regulation and their functional impact. The outcomes have great potential for providing us with new insights into mechanisms of transcriptional regulation. The results will be particularly relevant to interpretation of regulatory genetic variations. Ultimately, knowing the characteristics and conformations of enhancer architectures will increase our ability to link variation in non-coding DNA to phenotypic outcomes like disease susceptibility.

Mots-clés : transcriptional regulation,enhancers,enhancer rna
Projet ERC : FLUCTENZ (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1496875.0 €

Enzymes spin the wheel of life by catalyzing a myriad of chemical reactions central to the growth, development, and metabolism of all living organisms. Without enzymes, essential processes would progress so slowly that life would virtually grind to a halt, and the quest to determine their inner workings thus continues to attract and fascinate scientists over a broad range of disciplines. Cutting-edge methods now allow one to observe and manipulate individual enzymes in their reaction course. These revealed that chemistry at the single-molecule level is inherently stochastic and, at times, extremely unintuitive. Thermal fluctuations push enzymes to vibrate erratically and force a probabilistic description, but classical approaches are deeply entrenched in determinism, and so is our basic expectation for how things should behave in the world around us. The groundbreaking purpose of this proposal is to bring advanced theoretical methods and mathematical tools to the analysis of stochastic fluctuations of enzymes and proteins at the single-molecule level. These will be based on state-of-the-art approaches in statistical physics and stochastic processes that I will adapt and further advance to need. Equipped with mathematical techniques that have so far been foreign to the field, I expect to rectify fundamental flaws in our understanding, predict the emergence of novel phenomena, and show how single-molecule fluctuations can be extracted from bulk, steady-state, concentrations—despite belief that this is fundamentally impossible. Novel analysis methods that I will apply to tens of thousands of protein structures would complement these efforts and aid in the discovery of unifying principles governing thermal fluctuations of enzymes and proteins. The amalgamation of all these efforts will pave the way to large-scale, multi-tier, characterization of fluctuations which is expected to transform our understanding of enzymes and enzymatic catalysis.

Mots-clés : single molecule enzymology,noise and fluctuation phenomena,stochastic processes,first passage time processes,queueing theory,gaussian network model,physics of fractal systems
Projet ERC : 3DEpi (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 : 2440262.5 €

Epigenetic inheritance entails transmission of phenotypic traits not encoded in the DNA sequence and, in the most extreme case, Transgenerational Epigenetic Inheritance (TEI) involves transmission of memory through multiple generations. Very little is known on the mechanisms governing TEI and this is the subject of the present proposal. By transiently enhancing long-range chromatin interactions, we recently established isogenic Drosophila epilines that carry stable alternative epialleles, defined by differential levels of the Polycomb-dependent H3K27me3 mark. Furthermore, we extended our paradigm to natural phenotypes. These are ideal systems to study the role of Polycomb group (PcG) proteins and other components in regulating nuclear organization and epigenetic inheritance of chromatin states. The present project conjugates genetics, epigenomics, imaging and molecular biology to reach three critical aims. Aim 1: Analysis of the molecular mechanisms regulating Polycomb-mediated TEI. We will identify the DNA, protein and RNA components that trigger and maintain transgenerational chromatin inheritance as well as their mechanisms of action. Aim 2: Role of 3D genome organization in the regulation of TEI. We will analyze the developmental dynamics of TEI-inducing long-range chromatin interactions, identify chromatin components mediating 3D chromatin contacts and characterize their function in the TEI process. Aim 3: Identification of a broader role of TEI during development. TEI might reflect a normal role of PcG components in the transmission of parental chromatin onto the next embryonic generation. We will explore this possibility by establishing other TEI paradigms and by relating TEI to the normal PcG function in these systems and in normal development. This research program will unravel the biological significance and the molecular underpinnings of TEI and lead the way towards establishing this area of research into a consolidated scientific discipline.

Mots-clés : polycomb,3d chromosome organization,chromatin,gene expression,hi c,microscopy,drosophila genetics
Projet ERC : PATER (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Stockholm University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Epigenetic inheritance may not only occur in plants and fungi but also in mammals. While the effect of maternal lifestyle and in utero exposures is well studied, paternal epigenetic inheritance is a novel research field, especially in regard to chemical exposures. Many environmental pollutants exhibit anti-androgenic function. Despite the vital role of androgens in spermatogenesis, the effects of adult anti-androgen exposure on the sperm epigenome and offspring phenotype have been scarcely studied. The overall aim of this novel project is to increase the understanding of if, and how, male life experiences such as adult exposure to the anti-androgenic model substance and pollutant DBP (di-n-butyl phthalate) may affect offspring through paternal epigenetic inheritance. I accomplish this by integrating animal and human studies, using RNA-sequencing and mass spectrometry-based peptidomics to identify DBP-induced alterations in the sperm transcriptome and peptidome, examine noncoding RNAs and peptides role in embryogenesis, development and long-term health of the offspring in two generations. To validate the mechanistic importance of the sperm molecular alterations microinjections of selected biomolecules into zygotes will be conducted. This is the first project to investigate multigenerational effects of adult male exposure to anti-androgens in detail, and investigate the role of the sperm peptidome in paternal epigenetic inheritance. Directly linking animal experimental data about paternal transmission to human studies is unique and necessary to determine causal connection between environmentally-induced biomolecular alterations in sperm and offspring phenotype. The project can contribute to ground-breaking mechanistic understanding of how male life experiences may affect offspring through epigenetic inheritance. The findings may also have important public health implications via new regulations of anti-androgenic chemicals and male preconceptional interventions.

Mots-clés : paternal epigenetic inheritance,paternal life experiences,peptidomics,sperm noncoding rna,sperm peptides,anti androgenic chemicals,epigenetics,fertility
Projet ERC : EPICAMENTE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Centre for Genomic Regulation — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG;CRG-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 1996904.0 €

Epigenetic regulation and metabolism are of great interest in cancer research. However, physical and functional connections between these two areas remain largely unexplored. While it is commonly believed that metabolites can randomly distribute inside the cell, recent evidence rather favors the hypothesis that production of certain metabolites in specific subcellular compartments orchestrates different cellular processes. EPICAMENTE aims at exploring whether the localization of enzymatic activities on chromatin can integrate cancer metabolism with chromatin remodeling to control epigenetic regulation and tumor progression. First, I aim at providing a dataset of chromatin-bound metabolic enzymes in a comprehensive panel of cancer cell lines. By combining a chromatin fluorescent reporter cell line strategy with epigenomic approaches, I will define the epigenetic and transcriptional scenarios orchestrated by chromatin-bound metabolic enzymes, and investigate their relevance in cancer cell proliferation. Performing genetic screenings with the chromatin fluorescent reporter cell lines will allow the identification of genetic interactors mediating the epigenetic role of chromatin-bound metabolic enzymes. In parallel, I aim to screen for small molecules able to counteract the epigenetic states mediated by those metabolic enzymes. Finally, I will validate my results in in vivo cancer models, thus adding an important translational aspect to the project, and opening up new opportunities for cancer therapy. The success of this project can impact our fundamental understanding of cellular and cancer biology. In most cases, the belief is that intracellular materials reside inside steady-state membrane-based compartments, which limit the interactions between different molecular pathways. By describing the role of chromatin-bound metabolic enzymes and discovering direct connections between cancer metabolism and epigenetic regulation, I will scrutinize this belief.

Mots-clés : cancer metabolism,genetic screening,small molecule screening,drug repurposing
Projet ERC : DeadorAlive (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
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 : 2499000.0 €

Epithelia are assemblies of multiple cells whose complex dynamic behavior relies on physical properties including jamming-unjamming mechanisms, active turbulence and active nematic principles. The homeostasis of epithelia is crucial to maintain barrier function and integrity while epithelial cells are constantly challenged by the environment. To face these challenges, epithelia are dynamics and have to deal constantly with cell renewal and apoptotic extrusion, whose balance is key for epithelia homeostasis. On top of this role in tissue homeostasis, cell extrusion is a major cause of tissue shape changes and tumor progression. Extrusion mechanisms can thus lead to different cell fates namely dead or live cells but the factors selecting different cell fates are unknown. Extruding cells and their neighbors experience various mechanical stresses that lead to cell shape changes and could determine the way cells are extruded and their fate. However, these mechanical stresses and their impact on tissue organization remain to be determined. From our recent study on emergent active nematic properties of epithelia, we hypothesize that mechanical constraints coming from the active forces generated by neighboring cells and the passive physical properties of the environment can determine the modes of cell extrusion and the fate of extruded cells. Here we propose to tackle the molecular mechanisms and physical principles that determine the manner by which cells are extruded and the collective response of surrounding cells, and to evaluate their contribution in tissue homeostasis, morphogenesis and tumor progression. By combining tools from soft matter physics, cell biology and engineering, our project will reveal how active and passive physical signals are overarching components of the behaviors of tissues at different temporal and spatial scales, and may further establish novel paths to understand the mechanobiology of epithelial tissues in normal and pathological conditions.

Mots-clés : mechanobiology,soft matter physics,active systems,cell mechanics,collective cell behaviors