Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CausalEarth (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Technische Universität Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1112593.61 €

CausalEarth is an interdisciplinary project, aiming to improve our understanding of the interdependencies between major drivers (modes) of climate variability by developing novel statistical causal inference methods for both observations and model data. Disentangling the interdependencies of the major modes, such as El Nino Southern Oscillation and the North Atlantic Oscillation, is key to understand regional climate, and essential for process-based climate model evaluation. The modes' interdependencies are characterized by common drivers, indirect effects, nonlinearities, regime-dependence, and heterogeneous spatio-temporal causal relations. Currently, observational analyses are mostly based on the correlation of scalar (one-dimensional) time series derived from regional averaging or principal component analysis, restricted to supposed causal regimes, e.g., the winter season or phases of multi-decadal climate indices, where dependencies are expected to be stationary. Such scalar correlation approaches fall short in capturing the modes' complex regime-dependent spatio-temporal causal interdependencies. CausalEarth will develop innovative methods to move (1) from representing complex phenomena as scalar indices to learning spatio-temporal features, (2) from supposing causal regimes to learning them from data, and (3) from correlation to causal dependencies. To this end, CausalEarth will combine recent developments in machine learning with causal inference algorithms. These methods will be used to infer the causal interdependencies and drivers of major climate modes from observations and to construct the next generation of causal metrics for climate model evaluation. CausalEarth will push the limits of what can be learned from observational data about causal relations and drive model development towards breakthroughs in projecting our future climate.

Mots-clés : causal inference,machine learning,modes of variability,climate model evaluation,gaussian processes,kernel methods
Projet ERC : EUROPINIONS (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
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 €

Causes and consequences of change in public opinion about Europe Public opinion towards European integration and the EU is divided, especially in the wake of the economic crisis. From being a consensus issue with stable and broad elite and public support across the continent, it is now a contentious issue with swiftly changing opinions. EU opinions include utilitarian considerations, identity issues, and emotions. These EU opinions matter for voting behaviour and for the future course of the EU and European democracies. The future of European integration needs public support and yet we know little about what drives and changes this support: we need to know why some people change their opinions about European integration while others do not, and what the consequences of these changes are in terms of electoral behaviour. This project studies the causes and consequences of EU opinions. Opinions may change in response to real world developments, domestic political factors, and personal experiences, but very importantly also in response to new information such as provided by the media and in interpersonal and network communication. This project develops and tests a Communication Model of Public Opinion Change and Consequences. The key question underlying this project is when, how, for whom, and with which consequences communication matters for changes in public opinion about Europe? To address this question, an innovative and interdisciplinary design is needed. This will be done in five integrated subprojects, bringing together research on public opinion and political behaviour from the fields of political sociology, political communication, and political psychology. It employs a range of research techniques (novel survey methodology, (automated) content analyses, social media analysis, and experimentation) in a cross-nationally comparative design. The applicant is a leading expert in research on political communication, public opinion, and European integration.

Mots-clés : public opinion,communication and media effects,electoral behavior
Projet ERC : BIOACTIVECOATINGS (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 23365.0 €

Cell culture is a method used for growing living cells artificially outside their natural environment under controlled conditions. It is used for a large range of applications such as studies of cellular functions, drug discovery, biotechnologies and regenerative medicine. Cell culture in vitro is generally performed on plastic substrates, especially multi-well plates or Petri dishes that are made of polystyrene, a very stiff and synthetic material. This stiff substrate can bias the experimental results and mask cellular responses. These culture conditions contrast drastically with the conditions of the cellular microenvironment in vivo, where the cells are surrounded by a soft extra-cellular matrix (ECM) that provides mechanical and biochemical signals. Bioengineers have recently made developments on hydrogels and surface coatings that better mimic the natural ECM and present: 1) a controlled stiffness in a more physiological range than plastic dishes and 2) active biomolecules (peptides, growth factors) that can target specific receptors and trigger cellular responses. However, to date, there are still very few commercially available alternatives to the traditional plastic plates for high throughput cell culture in more relevant conditions. Hydrogel-coated plates have begun to be developed but lack stability in time and are highly sensitive to hydration. The aim of the BioActiveCoatings project is to bring to the market surface-coated plates with a control over thickness, stiffness and presentation of bioactive molecules (peptide, growth factor). This innovative strategy based on the layer-by-layer assembly of biopolymers will be implemented on multi-well plates, which are compatible with biological assays and optical microscopy. The Lbl-coated multi-well plates will broaden the application of cell culture plates in research and industry for fundamental biological studies, production of biological molecules, diagnosis and regenerative medicine.

Mots-clés : surface coatings,multi well cell culture plates,nanoscale coating,bioactive molecule
Projet ERC : COMP-MICR-CROW-MEM (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2396584.57 €

Cell membranes form a highly complex and heterogeneous mixture of membrane proteins and lipids. Understanding the protein-lipid interplay that gives rise to the lateral organisation principles of cell membranes is essential for life and health. Thus, investigations of these crowded membranes is emerging as a new and exceptionally exciting frontier at the crossroads of biology, life sciences, physics, and chemistry. However, our current understanding of the detailed organisation of cellular membranes remains rather elusive. Characterisation of the structural heterogeneity in-vivo remains very challenging, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatio-temporal resolution. In recent years, computer simulations have become a unique investigatory tool for understanding the driving forces governing the lateral organisation of cellular membrane components and this “computational microscopy” has become indispensible as a complement to traditional microscopy methods. In this ERC project I will, using advanced computational microscopy, study the interaction of lipids and proteins in complex, crowded, membrane patches, to enable the driving forces of membrane protein sorting and clustering to be unravelled at conditions closely mimicking real cellular membranes. The specific objectives are: • To develop a novel computational microscopy framework for simulating biomolecular processes at multiple resolutions. • To use this new computational microscopy framework to investigate the driving forces of membrane protein sorting and clustering. • To provide a molecular view of realistic, crowded, biological membranes composed of hundreds of different lipids and proteins. The outcomes will enable subsequent studies of many different types of cell membranes based on forthcoming lipidomics studies and progress in structural characterisation of membrane proteins.

Mots-clés : biomembranes,molecular dynamics,multiscale modelling
Projet ERC : SymBreakOrganoid (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Friedrich Miescher Institute — Pays : Suisse — Rôle : PI
Acronyme de l'entité : FMI
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Cell-to-cell variability is an inherent property of populations of cells. As a starting point for symmetry breaking events, it is also an essential building block for self-organised pattern forming systems. Nonetheless, the sources and roles of cell-to-cell variability in symmetry-breaking events during collective cell behavior await a quantitative and mechanistic understanding. To obtain these insights, we will use a model system of intestinal organoids, which recapitulates most of the processes of morphogenesis and patterning observed in intestinal tissue. In this system, the symmetry-breaking event is observed when, despite all single cells in a growing organoid are exposed to uniform environments, only a fraction of cells acquires specific cell fates, generating asymmetric structures such as crypts and villi. This project aims to uncover the extent, sources, and consequences of cell heterogeneity. To this end, we will use advanced multiplexed imaging of intestinal stem cells in 3D organoid development to monitor quantitatively the behaviour of each single cell in the system. Initially, we will identify potential sources of cell-to-cell variability, such as the microenvironment or the cell cycle. Next, we will create models to identify predictors of symmetry breaking and patterning. In parallel, we will determine the extent of cellular heterogeneity by single-cell RNA sequencing during organoid formation. Finally, we will test if cellular heterogeneity is necessary and sufficient to induce symmetry-breaking of intestinal organoids by experimentally inducing and perturbing cell-to-cell variability. Thus, this research proposal will address a major question in developmental biology and collective cell behavior, namely how single cells exposed to a uniform growth-promoting environment generate asymmetric structures. Moreover, it will unravel how local interactions between single cells give rise to emergent, self-organized patterns.

Mots-clés : symmetry breaking,cell to cell variability,quantitative biology,intestinal oranoids
Projet ERC : SmartCells (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Institut Curie — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 150436.81 €

Cells are complex, autonomous genetic machines with rich information processing capabilities. Synthetic Biology builds on these properties to design novel, synthetic genetic programs in cells with the aim of benefiting humans. Yet, safety and efficiency issues require creation of synthetic circuits that are reliable over a large range of operating conditions and stable to all sorts of perturbations. This is a tremendous challenge for synthetic biologists, as the robustness of any circuit is limited by their high dependence on the cellular host machinery and the fundamental stochastic nature of gene expression. Taking inspiration from physics and engineering we have imagined a computer-based feedback loop that can remotely, in real-time, control the state of a synthetic genetic program running in cells. Here, we will combine microfluidics, optogenetics, structured illumination, inference methods and control algorithm into such a real time control device of gene expression for yeast cells. We will then study how cells can be controlled at different scales and with increasing levels of complexity from a simple circuit to a simple multicellular ecosystem. Specifically, we aim at: (1) Understanding the potential and limits of such a control method. We will ask to what extent robust control can be achieved at the single cell level over a broad range of operating conditions. (2) Taking control of complex circuits. In particular, we will take control of key genes of the large regulatory network in charge of yeast adaptation to osmotic stress and dissect their roles in setting the mechano-biology properties of yeast. (3) Taking control of multicellular systems. We will control the collective dynamics of a population of cells via single cell control at selected locations. This framework will establish solid scientific and technological foundations of a novel research area combining physics, engineering and synthetic biology to take control of living systems.

Mots-clés : systems biology,micro  and nano  systems engineering
Projet ERC : CHROMREP (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499404.0 €

Cells are continuously exposed to insults that can break or chemically modify their DNA. To protect the DNA, cells have acquired an arsenal of repair mechanisms. Proper repair of DNA damage is essential for organismal viability and disease prevention. What is often overlooked is the fact that the eukaryotic nucleus contains many different chromatin domains that can each influence the dynamic response to DNA damage. Different chromatin environments are defined by specific molecular and biophysical properties, which could necessitate distinct chromatin responses to ensure safe DNA damage repair. The aim of this proposal is to understand how diverse chromatin domains, and in particular the dense heterochromatin environment, shape the dynamic chromatin response to DNA damage. I recently developed locus-specific DNA damage systems that allow for in-depth analysis of chromatin domain-specific repair responses in Drosophila tissue. I will employ these systems and develop new ones to directly observe heterochromatin-specific dynamics and repair responses. I will combine these systems and state-of-the art chromatin analysis with high-resolution live imaging to dissect the DNA damage-associated heterochromatin changes to determine their function in repair -kinetics, -dynamics and -pathway choice. Deciphering the chromatin dynamics that regulate DNA damage repair in heterochromatin will have broad conceptual implications for understanding the role of these dynamics in other essential nuclear processes, such as replication and transcription. More importantly, understanding how chromatin proteins promote repair will be important in determining how cancer-associated mutations in these chromatin proteins impact genetic instability in tumours in the long run.

Mots-clés : heterochromatin,dna damage,double strand breaks,histone modifications,genetic instability
Projet ERC : DIRNDL (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Wageningen University & Research — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : WUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Cells in multicellular organisms organise along body and tissue axes. Cellular processes, such as division plane orientation, must be aligned with these polarity axes to generate functional 3-dimensional morphology, particularly in plants, where cell walls prevent cell migration. While some polarly localized plant proteins are known, molecular mechanisms of polarity establishment or its translation to division orientation are elusive, in part because regulators in animals and fungi appear to be missing from plant genomes. Cell polarity is first established in the embryo, but this has long been an intractable experimental model. My team has developed the genetic, cell biological and biochemical tools that now render the early Arabidopsis embryo an exquisite model for studying cell polarity and oriented division. Recent efforts already led to the unexpected identification of a novel family of deeply conserved polar plant proteins that share a structural domain with key animal polarity regulators. In the DIRNDL project, we will capitalize upon our unique position and foundational results, and use complementary approaches to discover the plant cell polarity and division orientation system. Firstly, we will address the function of the newly identified conserved polarity proteins, and determine mechanistic convergence of polarity regulators across multicellular kingdoms. Furthermore, we will use proteomic approaches to systematically identify polar proteins, and a genetic approach to identify regulators of polarity and division orientation, essential for embryogenesis. We will functionally analyse polar proteins and regulators both in Arabidopsis and the liverwort Marchantia to help prioritize conserved components, and to facilitate genetic analysis of protein function. Finally, we will use a cell-based system for engineering polarity de novo using the regulators identified in the project, and thus reveal the mechanisms that provide direction in plant development.

Mots-clés : cell polarity,cell division orientation,plant embryogenesis,arabidopsis thaliana,marchantia polymorpha
Projet ERC : Ubl-tool (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997717.0 €

Cells respond to external and internal stimuli by dynamically altering the functional status of existing proteins via post-translational modifications (PTMs). One of the most common and versatile PTMs in eukaryotic cells is represented by the covalent attachment of the 76-amino acid protein ubiquitin (Ub) to substrate proteins (ubiquitylation). Substrate modifications range from a single Ub moiety being attached to a protein of interest to complex polymeric Ub chains that can also contain Ub-like proteins (Ubls). Ubiquitylation plays pivotal roles in nearly all aspects of eukaryotic biology and cells dedicate an orchestrated arsenal of enzymes to install (writer proteins), translate (reader proteins) and reverse (eraser proteins) these modifications. The entirety of this complex regulatory system has been coined the Ub code. As many different human diseases, including different types of cancer and neurodegenerative diseases are being linked to dysfunctions in Ubl-related pathways, it is of utmost importance to decipher the Ub code. Within Ubl-tool we devise a modular and interdisciplinary chemical and synthetic biology platform for studying aspects of ubiquitylation that are challenging or impossible to be addressed by more traditional technologies. We will develop innovative toolkits for generating defined Ubl architectures, including mixed, branched and hybrid Ubl chains and we will apply these tools for identifying novel reader proteins as well as for studying the functional impact of these complex types of modifications on critical cellular processes. Given its fundamental importance in eukaryotic biology, the Ub system has attracted considerable interest and promise as therapeutic target. We aim at identifying new drug targets within the Ub system by developing in cellulo activity-based probes that allow profiling activities and specificities of Ub eraser enzymes, laying thereby the foundation for the discovery of next-generation therapeutics.

Mots-clés : genetic code expansion,post translational modifications,unnatural amino acids,chemoenzymatic approaches,ubiquitylation
Projet ERC : BIOMECANET (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2931628.0 €

Cellular and sub-cellular organisation at the micrometre length scale ultimately reflects the activity of molecular networks that harness chemical energy to perform precise mechanical work, create functional spatial gradients, and sustain timely temporal changes in molecular activities. In eukaryotic cell division, the biochemical oscillations of the cell cycle drive dramatic morphological changes of the cytoskeleton necessary for bi-orientation of chromosomes and for their subsequent delivery into two daughter cells. This mechanism is at the heart of biology, but it is poorly understood and hard to address because it involves out-of-equilibrium chemistry of many components and Brownian mechanics of the cytoskeleton. BIOMECANET’s extraordinarily ambitious goal is to unravel this interplay by re-engineering it in vitro and by modelling it in silico. To achieve this, BIOMECANET will mobilize an unrivalled catalogue of purified human proteins to reconstitute four fundamental and interlinked biochemical and mechanical protein networks: 1) the cell cycle oscillator with the spindle assembly checkpoint; 2) the metaphase spindle; 3) the chromosome bi-orientation machinery of kinetochores; and 4) the central spindle and its links with the actin cytoskeleton required for cell fission. Then, BIOMECANET will combine these reconstituted networks, integrating temporal control and mechanical forces to analyse the emergence of complex life-like biological function, thus elevating scale and scope of in vitro reconstitutions to an entirely new level. Crucial to the attainment of BIOMECANET’s long-term goals is the synergetic alliance of two biochemists having pioneered different types of biochemical reconstitutions in the complementary areas of cell cycle and chromosome biology (Musacchio) and the cytoskeleton (Surrey), and a theoretician having pioneered physically faithful modelling and simulation of intracellular systems (Nédélec).

Mots-clés : cell cycle,mitotic spindle,cytoskeleton,self organization,cell division,spindle architecture,mechanical network,biochemical network,active network,molecular motors,computer simulation,microtubules,in vitro reconstitution,kinetochore,fluorescence microscopy,force spectroscopy,droplet microfluidics,biochemical reconstitution,modelling,simulation,theory,central spindle,anaphase,metaphase,origami