Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MUSEUM (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
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 : 1249290.0 €

The goal of MUSEUM is to develop robust methods for the asymptotic analysis of unconventional multi-scale integro-differential equations from evolutionary biology and their connection with stochastic processes. These equations involve nonstandard nonlinear integral terms and, under specific conditions of small variance and long time, exhibit solutions that concentrate around one or multiple evolving points.  We will develop new methods for the asymptotic analysis of models with nonlinear reproduction operators, in the regime of small variance. In these models, the nonlinearity of the reproduction operator comes from sexual reproduction, involving two parents, as opposed to asexual reproduction, which only involves one parent and which can be modeled by linear operators. Both of these reproductive modes are relevant to many living organisms. A recent theory, that encompasses Hamilton-Jacobi equations offers robust methods for the asymptotic analysis of integro-differential models with linear asexual reproduction. However, these methods, relying on comparison principles and viscosity solution theory, prove inadequate in the case of nonlinear sexual reproduction. Nonlinear reproduction operators introduce new features, yet their analysis remains considerably underdeveloped. Their treatment requires a conceptual leap.  Addressing stochastic effects in small subpopulations, we will also analyse large population and long time limits of stochastic individual-based models in the small variance regime. In this way, we will palliate the inadequacies of Hamilton-Jacobi approximations.  The methods that we will develop through this project will offer theoretical biologists the opportunity to go beyond their current possibilities and explore new frontiers.

Mots-clés : asymptotic analysis,nonlinear integro differential equations,hamilton jacobi equations,models from evolutionary biology,stochastic individual based models,large population limits
Projet ERC : CHROMOGENEVO (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
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 : 2000000.0 €

Chromatin contributes to many important processes ensuring the proper functioning of eukaryotic cells. In addition, it shapes linear and spatial genome organisation, and specifies chromosomal regions including centromeres that play a key role for chromosome segregation. Chromatin-associated factors also fold the genome in 3D to enable the transfer of chromosomes during mitosis or to regulate gene expression. Chromatin composition is however not identical among eukaryotes. How differences in chromatin composition contribute to different linear and spatial genome organisations is largely unknown. We aim to address these unknowns in three non-overlapping aims focusing on Lepidoptera and other insects as a model system. First, we will investigate how the disruption of an essential chromatin-based epigenetic loop underlies a drastic case of centromere divergence. To this end, we will perform homology studies on centromere-specifying factors to correlate them with centromere profiles in representative insects that have convergently evolved a holocentric architecture (chromosome-wide centromeres) from monocentric ancestors (centromeres restricted to one chromosomal region). Second, applying a combination of genomics, microscopy and biophysical simulations in the holocentric moth Bombyx mori we will test how the chromosome-wide distribution of centromeres affects the spatial organisation of mitotic chromosomes. Third, using B. mori and exploiting extensive genomic datasets from related Lepidoptera we will investigate how unprecedented features in 3D genome organisation including a new chromatin compartment that we identified affect genome function and organisation over evolutionary time. With our proposal, we will reveal how changes in chromatin lead to reorganisation of essential genomic regions and shape the topology of chromosomes in 3D, and in turn how this spatial dimension influences genome structure across evolution.

Mots-clés : centromere,genome organisation,chromatin,mitosis,chromatin compartments,genome evolution,smc complexes,insects
Projet ERC : VOYAJ (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université de Leyde — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997345.0 €

The majority of the Universe’s star formation occurred shrouded in cosmic dust, making it extremely challenging—historically—to obtain a clear view of young (z≳2) galaxy assembly. While the Atacama Large Millimeter Array (ALMA) has already enabled significant progress – including pioneering work by the PI to directly image this dusty star formation in early galaxies – their existing stellar populations remain obscured. At the same time, our understanding of the molecular gas fueling that star formation is still limited to unresolved detections and/or biased tracers. Fortunately, we are on the verge of a breakthrough with the newly launched James Webb Space Telescope (JWST) and the imminent arrival of ALMA Bands 1&2. To this end, the PI has obtained a suite of competitive proprietary data on JWST, ALMA, and Band 1/2 pilot facilities. Fully capitalizing on this opportunity now requires a team of capable researchers. By leveraging this data and a novel resolved spectral energy distribution (SED) fitting technique, the proposed program will 1) reveal the hidden stellar populations in the dustiest young (z~2.5) galaxies for the first time, testing predictions from hierarchical galaxy formation; 2) detect and map the crucial CO(1-0) and CO(2-1) emission lines in a statistical sample of these same young galaxies, directly measuring their full cold gas reservoirs via state-of-the-art Bayesian modeling, and calibrating other less-well-understood gas tracers; and 3) push studies of dust and gas in galaxies to the earliest cosmic epochs (z>6.5), including detecting their molecular gas via CO(3-2)—one of the key science goals for ALMA Band 1—thus revealing how the most massive early galaxies grew so quickly. Given her demonstrated track record leading a group and the wealth of data secured, the PI is optimally placed to take advantage of this unique confluence of revolutionary instruments to provide a completely new view into how young galaxies built up their stellar masses.
Projet ERC : MATHLOCCA (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
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 : 1999203.0 €

Multiple experiments have demonstrated that chemical reactivity can be modified by collectively coupling molecules to electro-magnetic vacuum-modes of a cavity. This has led to a new interdisciplinary research field, often denoted as "polaritonic chemistry". Despite great effort, even key underlying theoretical mechanisms are not understood today. This has recently led to controversies about fundamental origins of the observations in the collective strong coupling regime.  The main goal of MATHLOCCA is to develop a first verifiable quantum many-body theory for the problem. The theory will be truly many-body, discovering new physics in molecular models with a large number of coupled electronic, nuclear, and photonic degrees of freedom. Recent breakthrough findings of the applicant will lead to an unconventional ansatz: The theory explains polaritonic chemistry without polaritons. Instead it relies on the concept of collectively modified local dark states. This "dark state chemistry" will explain how collective strong coupling can modify chemistry on the single-molecule level, a long-standing open question. MATHLOCCA is multi-disciplinary, discovering fundamental new quantum many-body physics in new types of electro-vibro-photonic models. This will lead to applications also in cold atom platforms.  A second main objective is to introduce a new numerical theory for general open quantum many-body simulations, in terms of an entanglement optimized density matrix unravelling. The key new paradigm is to dynamically optimize the unravelling of a density matrix into pure state trajectories, making the trajectories more amenable to classical representation. This new concept will radically shift capabilities for numerical simulations in polaritonic chemistry and beyond, while giving fundamental new insight on entanglement dynamics in open quantum many-body theory.

Mots-clés : polaritonic chemistry,quantum many body physics,non equilibrium dynamics,numerical methods
Projet ERC : switchDecoding (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université Louis-et-Maximilien de Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999825.0 €

Heterogeneity amongst isogenic cells is pervasive throughout biology. Recently developed single-cell omics approaches are beginning to systematically reveal the repertoire of functionally distinct cell subpopulations within metazoan tissues. Pathogens frequently encounter changing and often hostile environments. To adapt to these challenges unicellular pathogen populations also exhibit a large degree of cell-to-cell heterogeneity, which often affects the outcome of infections. Yet, despite the importance of this cell-to-cell variation, very little is known about the mechanisms that control the level of heterogeneity in pathogen populations or why some isogenic populations are more heterogeneous than others. The goal of switchDecoding is to unveil the path to cellular variation. To this end I will go beyond identifying and describing new subpopulations of cells and elucidate the molecular pathways that establish them and modulate the level of cellular heterogeneity. As a model I will study the mechanism responsible for creating heterogeneity in surface antigen expression in the unicellular parasite Trypanosoma brucei. Antigenic variation is a widely employed strategy by evolutionarily divergent pathogens to evade the host immune response. Using a multidisciplinary approach, I will develop and combine single-cell multi-omics, lineage tracing and CRISPR-Cas-based genome manipulation strategies to characterize the processes, pathways and molecules regulating antigen switching in T. brucei. A better understanding of the mechanisms affecting the level of heterogeneity within a pathogen population will enable us to better predict how pathogens adapt to environmental challenges, including those that lead to the emergence of drug resistance. In the future this knowledge will enable the development of novel intervention strategies: drugs that modulate cell-to-cell heterogeneity to facilitate the clearance of infections.

Mots-clés : antigenic variation,genome architecture
Projet ERC : RestoreGut (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Capital Region of Denmark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : RH
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 1999934.0 €

Associations between caesarean section (CS) and childhood asthma may be mediated through microbial changes. In 700 children followed prospectively from birth, I recently showed that microbial perturbations after delivery by CS explain the delivery mode-associated risk of developing asthma in the first 6 years of life. CS was associated with more than a doubled risk of later asthma and allergic sensitization as well as immense compositional changes in the gut microbiota. An increased asthma risk was only found in children born by caesarean section, if their microbiome did not normalize by age 1 year, suggesting that a healthy microbial maturation can alleviate the child’s increased asthma risk. Under the hypothesis that asthma risk from CS can be avoided by restoring the early gut microbiome, the proposed project will identify key environmental, dietary and host factors that help restoring a CS perturbed microbiome, map the compositional and functional potential of the CS microbial profiles, evaluate the role of the virome in the CS associations and perform co-cultures of key microbial consortia that may restore a healthy trajectory. Finally, I will perform murine experimental models to validate the findings and perform pilot studies on CS microbiota restoration by fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT) in newborns. This will be a truly translational research project, with the potential to go from clinical observations to mechanisms based on bioinformatics and microbiological laboratory work and experimental models and a pilot human trial to infer causal relationships with the perspective of developing a potential future intervention strategy. If successful, this strategy will be groundbreaking for understanding the microbiome’s role in asthma development after CS and in the future potentially lead to novel prevention strategies and targeted, efficient microbiota manipulation in children with early microbial perturbations.

Mots-clés : caesarean section,microbiome,asthma,allergy
Projet ERC : IGNITION (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 1714350.0 €

Human tissues can tolerate a series of mutations in tumor suppressors and oncogenes without necessarily transforming. Potential for tumor initiation is not only determined by such accumulated molecular defects but also by the capacity of each cell and tissue to deal with them. Intrinsic cell plasticity – i.e. the ability to change phenotypes by accessing alternative expression programs - appears to be one of the determining factors of the penetrance of oncogenic stresses. Yet, how cell plasticity contributes to tumorigenesis remains poorly understood, in part because we can hardly access tumor initiation in humans. With IGNITION, we propose to uncover mechanisms maintaining cell lineage integrity under oncogenic stress in humans and explore their therapeutic potential to delay tumor initiation. To do so, we propose to access tumor initiation in humans using samples from the standard of care of BRCA1/2 mutation carriers. We will reconstitute entire individual trajectories up to tumor initiation, taking advantage of our privileged access to bio-banked and fresh human samples through the Curie hospital. Serial sampling for individual patients will be paired to organoid avatars, to expand our ability to observe tumor initiation events. Combining high resolution single-cell transcriptomics and epigenomics, we will identify recurrent non-genetic determinants of tumor initiation and study their potential as breaks or accelerators of tumor initiation with Cas9/CRISPR approaches in organoid models. Finally, we will test two strategies for therapeutic intervention: (i) control cell lineage integrity by restraining plasticity of the epithelial cell compartments, or (ii) targeting predispositions to transformation. Our long-term goal is to build on this integrated appreciation of tumor initiation to propose therapeutic strategies to monitor and delay tumor initiation in patients with pre-disposition to cancer.

Mots-clés : breast cancer,plasticity,single cell epigenomics and trancriptomics,predisposition
Projet ERC : InOVationCS (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université Masaryk — Pays : Rép. Tchèque — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1995000.0 €

Software making decisions or controlling cyber-physical systems is ubiquitous, hence its correctness is of paramount importance. While the increasing complexity makes manual implementation extremely error-prone, verification can provide formal guarantees on correctness. Verification of hardware and software has seen many successes and industrialization, making systems safe and reliable and their development more efficient. Controller synthesis goes one step further and avoids the manual implementation, providing a correct-by-construction controller directly. Despite considerable advances, scalable solutions remain elusive here. Artificial intelligence and machine learning (AI/ML) provide scalable solutions to decision making, but at the cost of their reliability, making their verification even more pressing. Besides, the use of AI/ML gives rise to fundamentally new challeges since models, properties and controllers are now often based on data rather than design. Due to their “black-box” nature, the resulting systems are (i) even harder to verify, and (ii) not explainable enough to be responsibly deployed. The PI has been pioneering the use of learning in verification to bring together the best of both worlds, scalability and reliability. The main objective of InOVation&CS is to utilize the power of learning in verification and controller-synthesis to overcome both the traditional scalability challenges as well as the recent, data-driven ones. The key to bringing the two closer than ever is a paradigm shift towards explainability and utilizing structure stemming from the presence of intelligence (human or artificial) in the definition, analysis and solution of real problems, thus providing more information to the learning parts. InOVation&CS shall provide new, more applicable and more scalable methodology for producing guaranteed reliable controllers. Keywords: verification, model checking, Markov decision processes, stochastic games, temporal logics

Mots-clés : verification,model checking,markov decision processes,stochastic games,temporal logics,artificial intelligence,decision trees,reinforcement learning,neural networks
Projet ERC : BioPhage (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Université Masaryk — Pays : Rép. Tchèque — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1992976.0 €

In 2017, the World Health Organization declared Staphylococcus aureus to be an antibiotic-resistant pathogen for which new therapeutics are urgently needed. Upon infection, S. aureus forms biofilms that can only be treated by the long-term application of several antibiotics in high doses or the surgical removal of the infected tissues. An alternative approach, phage therapy, has not been approved for clinical use, because the effects of phage infection on a biofilm are not sufficiently characterized. We propose to study the dynamics of the propagation of Herelleviridae phage phi812 in a S. aureus biofilm and molecular details of phi812 replication in a cell. We integrated a microfluidic system into a light-sheet microscope to enable continuous multi-day observation of the phage infection of a biofilm. We will determine how sub-populations of metabolically dormant or phage-resistant cells in a biofilm provide herd immunity against phi812 infection. Our system enables the fixation of biofilm segments for subsequent correlative imaging by serial block-face scanning electron microscopy to identify the interactions of phages with bacterial cells. We will use focused ion beam milling together with cryo-electron microscopy and tomography to determine high-resolution structures of previously uncharacterized phi812 replication and assembly intermediates in S. aureus cells. We will study the function of bacterial membranes and macromolecular complexes in the initiation and completion of phage genome delivery, the assembly of phage portal complexes and heads, and the mechanisms of genome packaging and head-tail attachment. This proposal’s biological significance lies in its focus on the as-yet uncharacterized interactions of phages and bacteria under biologically and clinically relevant conditions. Our analyses of phage spread in a biofilm, herd immunity against phage infection, and phage replication in cells may identify approaches for making phage therapy more effective.

Mots-clés : virus,phage,bacterium,infection,biofilm,biofilm matrix,therapy,lightsheet,fluorescence,microscopy,fluorescent protein,cricpr cas,genetic modification,recombinant,time lapse,imaging,development,antibiotic resistance,herd immunity,serial block face microscopy,correlative imaging,cryo electron microscopy,tomography,single particle reconstruction,focused ion beam milling,in situ,genome ejection,replication,head assembly,replication factories
Projet ERC : RUNES (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Northeastern University London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : NCH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1996580.0 €

In the last two decades, network science has revolutionized our understanding of diverse biological, social, and technological systems, becoming a cornerstone across various scientific and technological domains. Traditional network models, however, predominantly focus on pairwise interactions, often overlooking the complexity of higher-order interactions (HOIs) that involve more than two elements. This oversight is significant, as emerging evidence increasingly demonstrates that HOIs are not only prevalent but also critically influence the emergent behaviors of complex systems, thereby impacting our ability to comprehend and forecast their dynamics.  RUNES aims to pioneer a novel paradigm in network science, tailored to the intricacies of higher-order systems. This project will develop a holistic mathematical, methodological, and empirical framework to effectively understand, predict, and manipulate HOIs. This will involve redefining existing network models to incorporate higher-order interactions, combining information-theoretic and topological perspectives, and formulating new dynamical processes on these advanced substrates.  Concurrently, RUNES will innovate in developing model-informed statistical methods for inferring HOIs from data, enabling us to discern their unique structures and functions. This framework will be applied in two groundbreaking contexts: firstly, in experimental behavioral science, where we will quantify the impact of HOIs in controlled human group experiments; secondly, in neuroscience, where we will investigate the higher-order functional topology of the brain across various conditions, ages, and species.  RUNES’ new science of higher-order real-world complex systems will directly impact how we think about and deal with structural and dynamical patterns in many contexts, including epidemiology, artificial intelligence, economy and medicine.

Mots-clés : topological data analysis,higher order networks,computational modeling,group interactions,neuro ecology,neural architectures,functional brain connectivity