Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RegenerFuse (Horizon Europe, appel 2025, Consolidator grants)
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999855.0 €

Skeletal muscle fibers are highly organized multinucleated cells that grow and regenerate by fusing with myocytes derived from their resident stem cells. The fusion between myocytes and mature muscle fibers, which underpins the remarkable adaptability of muscles, is molecularly distinct from the fusion events that occur during development. This secondary fusion process, also known as myonuclear accretion, integrates mononucleated myocytes into immature myotubes or mature fibers, supporting muscle growth, repair, and regeneration throughout life. Despite its critical physiological importance, the mechanisms governing secondary fusion and the active role of myofibers in this process remain poorly understood.  Leveraging the development and application of high-content screening, advanced biochemistry, genetics, cell biology, transcriptomics, and cutting-edge imaging techniques, including 3D correlative light and electron microscopy (CLEM), we aim to provide groundbreaking insights into the molecular and cellular processes of secondary fusion. To achieve this, we will address three independent but interconnected aims:  Aim 1: Screen for regulators of secondary fusion and determine their effects using high-content imaging together with exploratory molecular studies.  Aim 2: Elucidate the molecular mechanisms and cellular dynamics underpinning fusion hotspots.  Aim 3: Establish the physiological relevance of myonuclear accretion in vivo by visualizing fusion hotspots and evaluating the impact of enhanced myoblast transplantation on muscle regeneration and function.  This synergistic approach will transform our understanding of muscle physiology, bridging the molecular mechanisms with their functional outcomes. The findings promise to uncover new principles of cell fusion, organelle dynamics, and tissue adaptability, offering profound implications for muscle biology and novel therapeutic strategies for muscle-wasting diseases.

Mots-clés : myocyte to myofiber fusion,cell fusion,myonuclear accretion,skeletal muscle,correlative light and electron microscopy clem
Projet ERC : SiGMA (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Sorbonne Université — Pays : France — Rôle : Partner
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 167625.06 €

This project is driven by M-theory, String theory in theoretical physics and the Minimal Model Problem in algebraic geometry. We study singular Kähler spaces with a focus on their special structures (of a differential geometry nature) and their interaction with various areas of analysis. To be more specific, we search for special (singular) Kähler metrics with nice curvature properties, such as Kähler-Einstein (KE) or constant scalar curvature (cscK) metrics. The problem of the existence of these metrics can be reformulated in terms of a Monge-Ampère equation, which is a non-linear partial differential equation (PDE). The KE case has been settled by Aubin, Yau (solving the Calabi conjecture), and Chen-Donaldson-Sun (solving the Yau-Tian-Donaldson conjecture); the cscK case has been very recently worked out by Chen-Cheng (solving a conjecture due to Tian). However, these results only hold on smooth Kähler manifolds, and one still needs to deal with singular varieties. This is where Pluripotential Theory comes into the play. Boucksom-Eyssidieux-Guedj-Zeriahi and the author, along with Darvas and Lu, have demonstrated that pluripotential methods are very flexible and can be adapted to work with (singular) Monge-Ampère equations. Finding a solution to this type of equations that is smooth outside of the singular locus is equivalent to the existence of singular KE or cscK metrics. At this point a crucial ingredient is missing: the regularity of these (weak) solutions. The main goal of SiGMA is to address this challenge by using new techniques and ideas, which might also aid in tackling problems in complex analysis and algebraic geometry. The PI will establish a research group at her host institution focused on regularity problems of non-linear PDE’s and geometric problems in singular contexts. The goal is to create a center of research excellence in this topic.

Mots-clés : k hler manifolds,monge amp re equations,pluripotential theory,envelopes
Projet ERC : CosmicLeap (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Trinity College — Pays : Irlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1993995.0 €

The explosive deaths of white dwarfs are essential in heavy element nucleosynthesis, galaxy feedback, and for understanding the evolution of binary systems. Type Ia supernovae (SNe Ia) are famous for their key role as cosmological-distance indicators and in the discovery of the accelerating Universe. Recent high-cadence surveys, and theoretical advances, have hinted that SNe Ia may not be the dominant way in which white dwarfs explode, with the potential existence of large populations of faint and rapidly evolving white-dwarf explosions. These unexplored classes of exotic transients may come from white dwarfs being torn apart by intermediate-mass black holes, mergers with neutron stars, or collisions in triple systems, but the mapping between explosions and observed transients is undetermined. This project aims at providing the first complete census of the multiple ways that white dwarfs explode by mapping their observations to their explosion physics and constraining their diversity. This sample will be crucial for defining optimal samples of SNe Ia for cosmology, as well as determining the rates and contributions of white-dwarf explosions to the origin of the elements. We will achieve this by i) obtaining the largest ever, rapidly discovered and spectroscopically confirmed sample, of white-dwarf transients with detailed follow-up observations, ii) the application of machine-learning techniques (e.g., neural-network emulators) for rapid comparison to sophisticated explosion models, and iii) the determination of the rates and diversity of their explosions in different galaxy environments. The confirmation and exploration of the multiple explosion channels for producing normal SNe Ia and exotic white-dwarf transients will have major implications for their nucleosynthetic yields, their use in cosmology, as well as predicting rates of double white dwarfs that will be detected in huge numbers in the Milky Way by the gravitational-wave detector, LISA.

Mots-clés : transient,white dwarf,survey,supernova,nucleosynthesis,cosmology
Projet ERC : PiezoMac (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes Engineering
Entité participante : Trinity College — Pays : Irlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2579608.0 €

Cardiac injury in the form of a myocardial infarction leads to cardiac muscle death and replacement scar tissue that cannot compensate lost heart tissue. This disease does not improve with traditional drugs and places significant burden on healthcare budgets worldwide; with a reduced quality of life for patients, often leading to heart failure. Current engineered cardiac patches do not reduce inflammation and do not integrate in a sufficient manner to compensate the pumping power lost with the heart tissue. The PiezoMac patch differs fundamentally from patches reported up to now. It will contain an optimised piezoelectric capability that will yield electric fields generated by the stretching of the heart. This electric field stimulation will be optimised to drive immunomodulate and regeneration of the cardiac muscle. The shape of the patch is predesigned using finite element modelling to conform the directional dependent stretching of the heart wall; with information of patient anatomy and extent of heart attack damage derived from X-ray CT and MRI scans. These smart patches will be 3D printed (using melt electrowriting) into accurate microfibrous ordered patches whose density, micro-orientation and fibre laydown will be informed using in silico modelling of piezoelectric generation and mechanical anisotropy. We will shortlist candidate mesh designs to match the anisotropy of the heart using finite element analysis, and refine the design process using a Bayesian Optimisation approach to strike a balance between mechanical anisotropy and piezoelectric output, and ultimately halt cardiac deterioration. This pragmatic and rational approach gathers and advances cutting-edge technologies in this interdisciplinary project to address a significant unmet need in healthcare today.

Mots-clés : immunomodulation,piezoelectric materials,biomaterials,auxetic materials,mechanical anisotropy,additive manufacturing,finite element analysis,electric field modelling,macrophages,bayesian optimisation,innate immunology,regeneration,machine learning,in vitro model,
Projet ERC : FAIM (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Trinity College — Pays : Irlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1994849.0 €

Symmetry plays an important role in our current understanding of nature. For instance, in the development of the Standard Model of particle physics the understanding of the gauge group of symmetries was crucial. There is a class of models, called integrable systems, which have so many symmetries that they are exactly solvable. Such models have the exciting possibility to be understood in all aspects and thus give valuable insights into physical phenomena. In this way integrable models offer a unique approach to tackling open problems in physics, such as, for instance, describing strongly coupled systems.  The aim of this proposal is to develop a new method to find and classify new integrable systems. Our approach is based on a new framework which was very recently put forward by the PI and his group. This new approach was applied to models that are closely related to regular integrable systems from string theory, quantum field theory and condensed matter physics. Several new models were discovered in this way but their physical and mathematical properties still remain to be understood. FAIM will be particularly focussed on models that have long-range interactions. These models are crucial in understanding strong coupling behaviour in for instance integrable models that appear in the AdS/CFT correspondence. Understanding long-range interactions is paramount to the computation of correlation functions in these models. Long-range interactions are also important for quantum systems in condensed matter such as cellular automatons.  More generally, integrable structures appear in basically all areas of physics. For this reason, finding new integrable models and classifying them will have a large multidisciplinary impact, with exciting applications ranging from condensed matter to string theory. This will potentially help us understand physical phenomena in various different fields.

Mots-clés : integrable models,quantum algebras,gauge string duality
Projet ERC : PRESERVARE (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Study of the Human Past
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 1997168.0 €

In the early modern period, large-scale food conservation practices such as fermenting, smoking, and pickling were crucial for globalizing trade and increasing food security, and thus for economic and demographic growth in Europe’s cultural trading hubs. In addition, recent research indicates that domestic and trade practices like food conservation were key to the development of natural philosophical and chemical knowledge and vice versa. Yet we still know very little about how knowledge on early modern food conservation was produced, adapted, and circulated across these domains. How can we retrieve and understand embodied, practical historical knowledge through the history of early modern food conservation? How did embodied, practical knowledge of food conservation develop in conjunction with formalised, scholarly knowledge? Who were the people who produced and circulated these two types of knowledge and to ensure food supply before the industrial revolution? PRESERVARE (‘to preserve’) answers these questions through case studies on 1) fermenting, 2) smoking, and 3) brining, curing, and pickling. It employs a theoretical framework rooted in the history of science, and a ground-breaking interdisciplinary approach that combines classical historical source interpretation with digital information extraction, archaeological data analysis, and physical reconstructions of early modern large-scale food conservation practices. Addressing these questions is urgently needed for the development of the history of knowledge, and is possible now because of recent developments in digitisation and information extraction, and theoretical and methodological advances in historical research. The project provides a history of early modern food conservation in the Low Countries in a global context, plus a theoretical and methodological framework for the historical study of dispersed epistemic domains and the retrieval and analysis of embodied, practical historical knowledge.

Mots-clés : food conservation knowledge archaeology reconstructions
Projet ERC : EvolSWARM (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 2130739.0 €

Our view of microbes has recently undergone a paradigm shift (the so-called ‘microbiome revolution’). Previously seen as unwanted harbingers of disease, it is now widely recognised that microbes can be beneficial and that the millions of microbes living in and on the bodies of animals and plants (i.e., the microbiome) can have profound effects on host biology. However, with the exception of the human vaginal microbiome, the microbiome revolution has largely overlooked the reproductive microbiome. This is especially true for wild animals. Yet, if we are to understand the evolutionary significance of host-associated microbiomes it is critical to study them in natural populations, where hosts exhibit greater genetic variability and are exposed to greater levels of environmental and microbial complexity. The aim of this proposal is to determine whether reproductive microbiomes impact host fitness and evolution in wild animals, and reveal the role of host genetics and immune functioning in shaping reproductive microbiome variability. I will leverage a unique wild system – the house sparrow – that can be studied in natural populations and in the lab, and for which I have recently pioneered the use of microbiome transplant techniques that allows me to disassemble and reconstitute natural microbiomes of nestlings. First, I will determine the fitness consequences and heritability of reproductive microbiomes in a wild population. Second, I will validate the impact of reproductive microbiome variability for reproductive success using novel in vivo microbiome transplants. Third, I will uncover the genetic basis of reproductive microbiome variation. Fourth, I will establish whether host immune functioning shapes reproductive microbiome composition. Altogether, I will significantly advance our understanding of the causes and – more importantly – the consequences of reproductive microbiomes for host biology and evolution.

Mots-clés : reproductive microbiomes,bird,reproductive biology,sperm biology
Projet ERC : VirIm (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Académie royale néerlandaise des arts et des sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Viruses are simple replicative units built from two components: a nucleic acid and a small number of associated proteins. Upon entering a cell, viruses co-opt the hosts machineries to copy their genetic material, while shutting down the hosts antiviral immune response. The success of viral infection differs dramatically from cell to cell through poorly understood mechanisms, resulting in heterogenous propagation through tissues, and ultimately, heterogeneous disease progression.  Although viruses have been studied for decades, the earliest steps of cellular infection have remained hidden, because only a few viral molecules are present at this stage, which presents formidable challenges for molecular analyses. Yet these initial events are critical for achieving a successful infection; transcription, translation and replication must be perfectly balanced to rapidly scale virus production before antiviral signalling pathways are activated. To overcome this barrier, we recently developed a first-in-kind imaging technology for simple positive-sense single stranded RNA (+ssRNA) viruses that transforms our ability to visualize early viral infection processes. In this proposal, we will expand our single–molecule toolbox to gain molecular insights into early viral infection of the more complex group of negative-sense RNA (-ssRNA) viruses. We will focus on the respiratory syncytial virus (RSV), a -ssRNA virus which can be deadly in infants and vulnerable adults, and lacks effective treatments. Specifically, we will determine i) how viral transcription and replication are coordinated on single viral genomic RNA molecules to optimize early viral propagation, ii) what causes the early viral infection heterogeneity, and iii) how heterogeneity in early viral infection impacts infection outcome. Using our novel approaches, we will gain a deep understanding of viral biology, which will eventually inform therapeutic interventions.

Mots-clés : single molecule imaging rna virus quantitative biology
Projet ERC : KINTSUGI (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Bordeaux — Pays : France — Rôle : PI
Acronyme de l'entité : UBx
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1978475.0 €

Air pollution, exacerbated by heatwaves and wildfires, affects primarily the lungs, leading to potentially life-threatening effects eluding conventional treatments. In response, KINTSUGI adopts a new perspective by exploring lung resilience mechanisms, to understand how respiratory health is maintained in most individuals: drawing on evidence from both a broad evolutionary standpoint, where humans have evolved in environments exposed to particles and proofs of lung resilience observed particularly in smokers, it seeks to redefine the paradigm of investigating lung response to particulate pollution. For that, KINTSUGI focuses on the airway submucosal gland (SMG), an ectodermal appendage lining the airways, renowned for its unique properties in mucus secretion, antimicrobial activity and a potential niche for proximal airway stem cells. The hypothesis posits the airway SMG as a crucial signalling hub, orchestrating responses to external perturbations to ensure proximal lung resilience. Using dissected clinical samples of SMG, it aims to unravel cell interactions intricacies within this niche, ultimately generating a "SMG-related resilience signature". Additionally, 3D in vitro models replicating the in vivo architecture and function of airway SMGs will be established for the study of mucociliary clearance, antimicrobial activity, and regeneration studies under both homeostatic conditions and particles exposure. KINTSUGI further integrates probabilistic mathematical modelling, considering microscopic interaction rules within the SMG, to elucidate macroscopic behaviours underlying lung resilience at different time scales. KINTSUGI anticipates impacting broader scientific communities, as such health, biology, and evolution, by uncovering fundamental insights into the mechanisms governing resilience. The impact on health and its potential to resonate across diverse scientific disciplines positions KINTSUGI as a ground-breaking initiative with far-reaching implications.

Mots-clés : lung resilience,particulate pollution,airway submucosal gland,lung organoid
Projet ERC : PrApEDoC (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1999625.0 €

Epithelial cell death is widespread during development and tissue homeostasis. While the core pathway of apoptosis is well known, we lack predictive power to understand when and where a specific cell will die in a tissue. Yet, this should have important consequences for clone selection and tissue homeostasis, as exemplified by the process of cell competition. This context dependent cell elimination is essential for tissue homeostasis and tumour progression, but we know very little about its prevalence during normal development. Recent works have characterised multiple non-apoptotic functions of effector caspases and a high frequency of cells undergoing transient caspase activation without death. Yet, what distinguishes a dying from a surviving cell downstream of effector caspase activation is completely unknown. Using quantitative live imaging of effector caspase sensors and caspase activity tuning by optogenetics in the Drosophila pupal notum (a single layer epithelium), we found that cells engage in apoptosis at very variable levels of effector caspase activity. This suggested that the engagement in apoptosis can be developmentally modulated downstream of the most terminal caspase activation and that a completely new layer of regulation of cell death could have important physiological roles. Here, we propose to combine quantitative live imaging, multivariate model, supervised machine learning and quantitative perturbations through optogenetics to define parameters predictive of the engagement in apoptosis downstream of caspase activation. We will then use spatial omics combined with an optogenetic based screening to identify new factors modulating the sensitivity to caspases. Eventually we will unravel the physiological functions of caspase sensitivity modulation by defining a new paradigm of physiological cell competition and clone selection, and characterising its impact on tissue morphogenesis and oncogenic cell elimination.

Mots-clés : apoptosis,caspases,cell competition,optogenetics,drosophila,epithelium,cell decision,multivariate models,machine learning