Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : X-MESH (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Nantes Université — Pays : France — Rôle : Partner
Acronyme de l'entité : NU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 266250.0 €

This project will develop an innovative approach, X-MESH, to overcome a major difficulty associated with engineering analysis: we aim to provide a revolutionary way to track physical interfaces in finite element simulations using extreme deformation of the meshes.  Unprecedented low computational cost, high robustness and accuracy are expected as the proposed approach is designed to avoid the pitfalls of the current methods, especially for topological changes. The key idea of the project has emerged in a synergistic brainstorming between J.-F. Remacle (meshing methods) and N. Moës (computational methods). This key idea is to allow elements to deform up to zero measure. For example, a triangle can deform to an edge or even a point. This idea is rather extreme and totally revisits the interaction between the meshing community and the computational community who, for decades, have striven to interact through beautiful meshes. Six areas in fluid and solid mechanics as well as heat transfer are targeted. Interfaces will be either (i) material, i.e. attached to particles of matter (the interface between two immiscible fluids or the dry interface in a wetting and drying model) (ii) immaterial, i.e. migrating through the material (a solidification front, contact front, yield front in yield stress fluid flow or a crack front). Successes brought by X-MESH are expected in the following engineering areas: safety design and maintenance, manufacturing processes, coastal engineering, energy efficiency, ocean modeling to cite a few. The project takes place in a stimulating environment mixing senior staff with PhDs and Post-docs to produce and disseminate publications with open source pieces of software. It also intends to create a synergy at large with the computational communities dealing with interfaces and fronts in all fields of science: topology optimization, superconductivity, tissue growth, hydrogel swelling, crystal growth, ferroelectric crystal etc.

Mots-clés : mesh generation,finite element analysis
Projet ERC : MitoContact (Horizon Europe, appel 2025, Synergy grants)
Entité participante : École polytechnique fédérale de Lausanne — Pays : Suisse — Rôle : CO-PI
Acronyme de l'entité : EPFL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 5321878.0 €

Mitochondria are central to modern eukaryotic life, but how they carry out their functions in space and time within the cellular milieu is remarkably enigmatic. Contributing to the complexity of this question, mitochondria face dual existential challenges: supporting their life cycle as self-reproducing, DNA-containing organelles; and supporting the energetic and signaling needs of the host cell. A universal feature in how mitochondria address these challenges is via engagement in membrane contact sites (MCS) - sites of intracellular signaling or biomolecular exchange - with partner organelles. Candidate MCS proteins between partners range into the hundreds, driving speculation that diverse contacts exist. However, technological limitations in measuring the composition, structure, dynamics and physiology of transient MCS have hindered progress in dissecting their functional diversity.  Our project will develop and apply cutting-edge technologies to investigate the dynamics and molecular organization of MCS, to reveal how individual contacts locally coordinate mitochondrial physiology and function. We will deploy (1) chemical biology “recorders,” enabling us to trace the history of MCS and physiology. We will combine this with (2) live-cell “smart microscopy,” driven by closed-loop feedback through real time neural-network recognition of cellular events, to capture dynamics with high specificity and spatio-temporal resolution and (3) cellular cryo-correlative microscopy to obtain structural snapshots and gain insights into MCS molecular architecture. We will focus on heterotypic and homotypic contacts implicated in mitochondrial proliferation, degradation, molecular exchange, and metabolic states. Our synergistic approach will allow us to screen for MCS inhibitors or stabilizers and measure the impact of disrupting contacts. Thus, we expect our project to have broader implications for therapeutics, and our tools to impact fundamental biological discovery beyond MCS.

Mots-clés : mitochondria,membrane contact sites,fluorescence microscopy,electron microscopy,cryo em,smart microscopy,super resolution microscopy,fluorescent biosensors
Projet ERC : TransFORM (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 7135726.0 €

Translation – the fundamental process of protein synthesis catalyzed by ribosomes - has been extensively characterized from a biochemical, structural, and mechanistic perspective. However, how exactly the translation machinery operates as an interconnected system of millions of ribosomes in cells is poorly understood. Within the cell, ribosomes associate with a multitude of regulatory proteins forming a variety of specialized complexes and distributing across cellular space in a manner that depends on cell state. What is the specific composition of those complexes, their significance, and their functional role? How are they defined and regulated by subcellular compartmentalization? How do they change in response to cellular stress? Our TransFORM synergy team brings together experts in method development for in-cell structural biology and the biology of translation to allow us for the first time to attack these fundamental problems. Building on our prior achievements, we aim to synergistically develop novel methods of cryo-electron tomography with imaging across scales in conjunction with crosslinking mass spectrometry and integrative structural modeling for near-atomic structure determination directly in cells. TransFORM will determine the ribosome structural and functional states across the translation cycle in human cells, following distinct 40S, 80S, and disomal particles (80S+80S), in and out of polysomes and across different protein synthesis regimes. We will uncover structural and compositional changes and regulatory mechanisms across cellular space, in adaptation to perturbations by stressors and during viral infection. Our model systems will span from single cells to organoids. TransFORM will provide a detailed and comprehensive in-cell map of the essential process of protein synthesis while delivering innovative methods for the next-generation of in-cell structural biology.

Mots-clés : in cell structural biology,translation,human cell models,ribosomes,heterogeneity,structural biology,cell biology,cryogenic electron tomography,crosslinking mass spectrometry,structural modeling,integrative modeling
Projet ERC : 2DPolyMembrane (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université technologique de Dresde — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TU Dresden
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3000000.0 €

Current separation technology is crucial for many aspects of human life and accounts for ~15% of the world’s energy consumption. While the particle flow through separation columns is directional at the atomistic scale, undirected Brownian motion dominates in state-of-the-art membranes. 2D membranes have the potential to overcome this intrinsic deficiency and shift the paradigm of particle transport from disordered Brownian motion to unidirectional flow. We will develop unprecedented 2D polymer heterostructure membranes (2DHMs) combined with functionalized graphene. They offer ultimate thinness (leading to shortest diffusion lengths), precision pore geometry/size (resulting in high size-selectivity, even for hydrogen isotopes), and high functionality (fostering chemical/charge selectivity and ionic gating), making them ideal membrane materials to realize selective and unidirectional ion transport. We will combine our complementary expertise in theory and prediction, chemical design, and on-water/liquid surface synthesis, as well as in-situ ion transport investigations to develop robust 2DHMs. We will synthesize 2DHMs in the form of horizontal and vertical heterostructures, for which reliable structure-property correlations will be established. We will take advantage of lattice vibrations, nuclear quantum, and electrochemical effects, and consequently reformulate classical diffusion theory to consider these game changers. As a result, we will achieve innovative 2DHMs for selective proton and ion transport with high permeance, laying the foundations for the next-generation membrane technologies. 2DPolymembrane will unlock the unique opportunities of 2DHMs for innovative energy device integrations (proton/aqueous metal batteries, fuel cells, and reverse osmotic power generators), where the merits of ultrathin precision 2DHMs will result in the highest selectivity and highest particle flow, and thus a fundamental device performance beyond the state-of-art.

Mots-clés : interfacial synthesis two dimensional polymer heterostructures hydron sieving ion transport separation membranes
Projet ERC : PEPS (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université de Heidelberg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3751698.75 €

Neural stem cell (NSC) populations in the vertebrate brain generate adult-born neurons for plasticity, growth, and repair. Neurogenic and gliogenic capacity, based on long-term NSC maintenance, functionally define “stemness”. Stemness embodies massive NSC heterogeneity at the single cell level and requires control of maintenance or differentiation decisions at the population level. These features remain mechanistically unreconciled. We hypothesise that spatiotemporal interactions among heterogeneous NSCs are coordinated to control the population behaviour. Thus, we propose a multi-dimensional project exploring these features in time and space, to decode the mechanistic principles of stemness. To this end, we bring together experimental and theoretical groups with complementary expertise in NSC biology, biostatistics and mathematical modelling. In an iterative experimental-mathematical approach, we will (1) solve the topology of individual NSC trajectories in transcriptomic space, (2) identify local cell-cell coordination mechanisms that impact these trajectories in situ, and (3) decode the resulting systemic properties and outputs of NSC ensembles at long-term and large spatial scales. This programme will result in original methods, including retrospective transcriptomics in single cells, innovative barcode transfers, and a novel mathematical framework to describe structured spatio-temporal population dynamics. We will focus on two biological model systems, the adult mouse ventricular sub-ventricular zone and zebrafish pallium, where NSC ensembles display comparable heterogeneity but differ in spatial organisation and fate dynamics. Together, PEPS will uncover the general principles and regulatory mechanisms of perpetuating stemness in time and space. It will lay the conceptual and methodological foundation to manipulate stem cell systems to improve their stability or output, and also produce new methods of universal value for studying cellular systems.

Mots-clés : adult neural stem cells,zebrafish pallium,ventricular subventricular zone,spatio temporal population dynamics,single cell multi omics,barcoded transfer connectome,brain injury,single cell perturbations,mathematical modelling,structured population models,partial differential equation,high dimensional statistics,dimension reduction
Projet ERC : i2B (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : AWI
Type d'entité : Recherche
Financement ERC de l'entité : 3044116.25 €

The Arctic Ocean is turning blue. Abrupt Arctic warming and amplification is driving rapid sea ice decline and irreversible deglaciation of Greenland. The already emerging, substantial consequences for the planet and society are intensifying and yet, model-based projections lack validatory consensus. To date, we cannot anticipate how a blue Arctic responds to and will amplify an increasingly warmer future climate, nor how it will impact the wider planet and society. Climate projections are inconclusive as we critically lack key Arctic geological archives that preserve the answers. This “Arctic Challenge” of global significance can only be addressed by investigating processes, consequences, and impact of past “greenhouse” (warmer than present) states. The timeliness of i2B is tied into retrieval of revolutionary, new Arctic geological archives of past warmth and key breakthroughs in climate model performance that will be integrated in a concerted framework beyond state-of-the-art. i2B will deliver a ground-breaking, synergistic framework to answer the central question: “Why and what were the global ramifications of a “blue” (ice-free) Arctic during past warmer-than-present-climates?” This will be addressed through three connected, cross-disciplinary objectives integrating the expertise, knowledge, and skill-sets of three PIs and their different Arctic paleo-climate and modelling teams. i2B will quantify cryosphere (sea ice, land ice) change in a warmer world (O1) that will form the scientific basis for understanding the dynamics of Arctic cryosphere and ocean changes (O2), to enable quantitative assessment of the impact of Arctic change on ocean biosphere, climate extremes and society (O3) that will underpin future cryosphere-inclusive IPCC assessments. i2B will solve the “Arctic Challenge” with the synergistic multiplier of the 3 PIs` expert capabilities providing pioneering knowledge on how a blue Arctic impacts Earth’s climate during greenhouse climate states

Mots-clés : arctic ocean,greenhouse climate
Projet ERC : BlackHolistic (Horizon Europe, appel 2022, Synergy grants)
Entité participante : University of Namibia — Pays : Namibie — Rôle : Partner
Acronyme de l'entité : UNAM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 482445.0 €

Black holes (BHs) are icons of the fundamental nature of gravity, the mysterious force shaping the Universe. They are also the Universe’s most efficient power houses, turning infalling gas into energy and outflows that, together with gravity, mould galaxies and thus ultimately stars and planets. The first image of a black hole by the Event Horizon Telescope (EHT), wherein we played a leading role, captured the imagination of scientists and the public alike. This picture of the immutable black hole is however blurred by the dynamic, still mysterious behaviour of the surrounding gas. Our limited understanding of these turbulent, magnetised plasma in/outflows, producing the radiation and high-energy particles we observe, obstructs a straightforward interpretation of the black hole image for testing theories of gravity. The challenge in understanding the astrophysics of black holes and their impact on the cosmos is that they span >8 orders of magnitude in mass, size and timescales, and emit light over 15 orders of magnitude in frequency. Our new approach overcomes this scale separation, by simultaneously addressing the dynamics of large and small black holes, in colour. We produce for the first time high-resolution multi-colour movies with the EHT combined with new telescopes probing the variable extremes of the electromagnetic spectrum (e.g., CTA, MeerKAT/SKA1). The data are analysed and interpreted with innovative models finally combining micro- and macrophysics. The PIs bring together complementary expertise over the entire black hole mass scale in radio imaging and multi-wavelength monitoring, astroparticle physics, and theoretical modelling to bear on the problem. This is accompanied by four major investments: construction of a new mm-wave telescope in Africa enabling full dynamical imaging of black holes with the EHT, new model development, supercomputing hardware, and a vibrant team of young scientists to help develop a new, truly universal black hole paradigm.

Mots-clés : black holes,event horizon telescope,radio astronomy,vlbi,grmhd simulations
Projet ERC : DynaTrans (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2123362.5 €

During mammalian embryogenesis, key events involving DNA and regulatory molecules over seconds and nanometers affect and are affected by, a major reorganization of the genetic material in the nucleus over hours and micrometers. How these scales are spanned and integrated into the course of development remains a major unresolved challenge. Progress in this quest is difficult, either because current model systems suffer from severe technical limitations or because existing analytical approaches probe individual spatial or temporal scales thus ignoring their evolving interactions. Traditional live imaging lacks the spatial resolution to accurately delineate chromosome organization at the scale of genes, while bulk molecular assays are ill-suited for studying development over time. Here, we propose a multi-disciplinary approach to the dynamics of developmental gene regulation to understand the details of the underlying mechanisms and their deployment over time. We combine and apply optical, molecular-genomic, and theoretical tools to recently available mammalian pseudo-embryos, allowing unprecedented precision in developmental staging, a large amount of material, and easy optical access. By focusing on select gene loci we track transcriptional activation and the interactions of distal DNA elements in real-time along with the associated chromatin dynamics using interaction profiles. Our datasets are iteratively distilled into mathematical models of increasing scope, converging towards an integrative dynamic polymer model that simultaneously captures long-timescale chromatin rearrangements as well as short-timescale motions of genetic regulatory elements and transcriptional activity. We then challenge these models via genome editing and temporally defined interventions by building light-controlled tools to affect the chromosome landscape. This project aims to reshape our view of how genes are regulated during mammalian development.

Mots-clés : gastruloids,pseudo embryos,live imaging,optogenetics,inference modeling,maximum entropy,nuclear architecture,loop extrusion,enhancers,regulatory landscapes,3rs principle
Projet ERC : BREAKDANCE (Horizon Europe, appel 2022, Synergy grants)
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 : 4857625.0 €

Understanding the establishment of an animal body plan is an important challenge of modern biology. Progress has been mainly limited by (1) a separation of research fields studying genetic and biophysical mechanisms, and (2) a lack of approaches to mimic multicellular tissue organization from first principles. In a cross- disciplinary effort, we will focus on the earliest stages of animal development, when first steps of cell differentiation define the primary body axis through spatial symmetry breaking, laying the foundation for the future body plan. Our goal is to identify the fundamental mechanisms controlling this symmetry breaking process. To this end, we will study in detail the interplay between global tissue geometry (shape, size, and dimension), physical boundary conditions, and mechano-chemical cell interactions. Therefore, we address the following questions: (i) How do global shape and size control local cellular states and interactions? (ii) How do local cellular states and interactions induce robust symmetry breaking at the tissue level? (iii) To which extent can geometry control cell fate specification in a species-independent manner? To overcome previous limitations, we will establish a comprehensive methodological toolbox of synthetic bottom-up approaches and functional ex-vivo assays. We use as model systems mouse, zebrafish, and later also human embryonic stem cells. This will be combined with advanced biophysical techniques and theoretical modeling in order to systematically dissect the mutual couplings between genetic patterning mechanisms and morphogenetic processes, thereby revealing the multicellular dance underlying tissue symmetry breaking. Our results will shed new light on the long-standing question of how complex biological forms are robustly built from a single fertilized egg, impacting on our understanding of organism development and maintenance, and opening new directions for the controlled design of artificial tissues and organs.

Mots-clés : biological self organization,tissue patterning,quantitative approaches to mechano chemical signalling,cell and tissue mechanics,size and shape in biology
Projet ERC : ClonEScape (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Institute for basic science — Pays : Corée du Sud — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Epithelial cancers are thought to evolve through a competitive process of mutation and selection in which the serial acquisition of oncogenic mutations confers an increasing fitness advantage, culminating in neoplastic transformation, tumour invasion, and metastasis. This programme often initiates through a phase of field cancerization in which mutant clones expand within the context of physiologically normal-looking tissue. To mitigate the risks associated with field cancerization, protection strategies have evolved that resist mutant clone expansion, from the development of anatomical features that limit clone growth to the activation of genetic and immunological surveillance mechanisms. Yet, despite these insights, our knowledge of how oncogenes act alone or in combination to evade these protection mechanisms to drive clonal pathogenesis remains largely unknown. Here, by combining a unique genetic lineage tracing strategy with comparative single-cell genomics and quantitative modelling-based methods, we will define the mechanisms that mediate mutant clone competition. By placing an emphasis on the squamous and columnar epithelia of the GI tract, we will investigate whether and how injury and inflammatory cues, as well as ageing, enable tumorigenic clones to evade natural protection strategies, functioning as a “second hit” in driving field cancerization and neoplastic transformation. Finally, to explore the translational relevance of our findings, we will combine DNA sequencing, single-cell methods, and spatial transcriptomics with the design and genetic manipulation of state-of-the-art 3D organ cultures to investigate mutant clone dynamics in human tissue. By tracing the origins of clonal pathogenesis, these findings promise insights into the design of new prevention, detection, and treatment strategies, targeting the early stages of cancer progression.

Mots-clés : intestine,stomach,oesophagus,liver,lineage tracing,mutant clone competition,injury induced cellular reprogramming,regeneration,cancer,ageing,advanced mouse genetics,human organoids,comparative single cell genomics,theoretical modelling