Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : COMPASS (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Université libre de Bruxelles — Pays : Belgique — Rôle : PI
Acronyme de l'entité : ULB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Epigenetic features are commonly dysregulated in cancer and one of the surprising findings from the sequencing of cancer genomes is the high rate of alterations in many epigenetic regulators. KMT2D/MLL4, KMT2C/MLL3 and KDM6A/UTX are among the most frequently mutated genes in a wide range of cancers and in normal aged epithelial cells. Interestingly, these three genes are components of the same complex, COMPASS-like complex that regulate enhancer activity and regulate gene expression in a lineage specific manner. The deletion of members of the COMPASS-like complex has been associated with altered differentiation, aging and tumorigenesis. However, the precise mechanisms by which mutations in these genes impact cell states during tissue homeostasis, tumour initiation, tumour heterogeneity and metastasis, remain poorly understood. To address these important questions, we will use multidisciplinary approaches that will combine in vivo single cell lineage tracing, single-cell genomics, epigenomics and transcriptomics, in vivo CRISPR-based gene editing, together with genetic and pharmacologic perturbations, to define in a comprehensive and integrated manner the impact of Kmt2d, Kmt2c and Kdm6a deletion on cell state dynamics during homeostasis, regeneration, early steps of tumour initiation, tumour heterogeneity and metastasis in skin squamous cell carcinoma and bladder cancer. Moreover, we will perform genome wide CRISPR-Cas9 screen to identify the synthetically lethal genes in KMT2D, KMT2C and KDM6A mutated cancer cells to uncover new tumour vulnerabilities that can be pharmacologically targeted.

Mots-clés : stem cell dynamics,epigenetic regulation,histone methyl transferases,compass like complex,clonal evolution,tissue regeneration,tumour initiation,tumour heterogeneity,metastasis,synthetic lethality,crispr screen,
Projet ERC : PASTIS (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Université libre de Bruxelles — Pays : Belgique — Rôle : PI
Acronyme de l'entité : ULB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1121513.75 €

The present proposal focuses on the role of microstructural disorder in the dynamics of many-particle systems. Due to the complexity of such systems, any practical description relies on simplified effective theories. In the tradition of Hilbert’s sixth problem, I aim at the rigorous large-scale derivation of effective theories from fundamental microscopic descriptions. In those derivations, the role of microstructural disorder has often been overlooked for simplicity. However, disorder is key to many systems and can lead to new behaviors. Understanding its effects in scaling limits of particle systems is, therefore, of fundamental interest.  I have selected five model problems illustrating important aspects of the topic. The simplest regime is that of homogenization, where the effect of the disordered background averages out on large scales. For systems like particle suspensions in fluids, microstructural disorder is itself induced by particle positions; as these evolve over time, adapting to external forces, it can lead to nonlinear effects. Another aspect is the emergence of irreversibility: the transport of mechanical particles in a disordered background typically becomes diffusive on large scales, which gives for instance a microscopic explanation for electrical resistance in metals. I also consider the more intricate problem of self-diffusion, where irreversibility rather results from interactions with the ensemble of other particles themselves. A last important aspect concerns the emergence of glassiness, which results from the competition between interactions and disordered background.  Mathematically, this proposal is at the crossroads between the analysis of partial differential equations and probability theory and it builds on tremendous recent progress in two of my fields of expertise: homogenization and mean-field theory. Their combination provides a timely and innovative framework for new breakthroughs on scaling limits of disordered particle systems.

Mots-clés : pde with random coefficients interacting particle systems disordered media microstructure scaling limits homogenization effective behavior mean field limits collective behavior kinetic limits irreversibility random drift particle suspensions flow induced microstructure active fluids quantum diffusion self diffusion thermalization lenard balescu equation
Projet ERC : EpiSex (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université de Stockholm — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499262.0 €

Sexual selection has two intuitive but overlooked implications for epidemics. First, infectious diseases spread when individuals contact each other. Reproduction is a major driver of contact: mate preferences should affect who contacts whom, and thus parasite transmission opportunity. Sexual selection research shows that choosers prefer mates with high quality ornaments, which generally indicate parasite resistance, but the predicted epidemiological consequence of such contact with more resistant individuals – that transmission slows – is untested. Second, choosers selecting mates that resist parasite infection may benefit indirectly as this increases the parasite resistance of their offspring. If choosers consistently produce offspring with the most genetically resistant mates, population-level parasite resistance should increase through generations: again, untested.  I will leverage essential existing knowledge and artificial selection lines of the Trinidadian guppy, its gyrodactylid parasites, and a successful workflow I have developed, to test how variation in female preference affects epidemics in three ways. First, I will run replicate experimental epidemics in groups of individually identified guppies, tracked using machine learning, in which females do, or do not prefer males with larger orange ornaments. These ornaments indicate parasite resistance in this system. Second, I will assay the offspring produced post-epidemic for parasite resistance and paternity. I predict that epidemics in which females prefer ornamented males will be slower, and the offspring produced will be more resistant to parasites. Finally, I will use the results from both experiments to refine a mathematical model. We will validate model predictions with surveys of natural populations known to vary in female preference for males with larger orange ornaments. The resulting framework of how sexual selection affects parasite transmission will improve our predictions of epidemic dynamics.

Mots-clés : disease ecology sexual selection trinidadian guppy parasite transmission epidemiology mate choice mate preference ornaments
Projet ERC : ALTREALITY (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Université de Stockholm — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1297878.0 €

Many people hold systems of wrong beliefs, which combine into a semi-coherent alternative reality based on the sinister motives of influential actors. I build models of the supply of and demand for such alternative realities. The key idea is that people believing in alternative realities misperceive not only features of the environment but also the incentives of other actors. Applications of my supply side framework include the analysis of political conspiracy theories that serve to discredit the intellectual elite, fear mongering to prompt mobilization in a conflict, and anti-state narratives that serve to generate political support for fiscal conservatism. My demand side approach formalizes the idea that individuals believe in alternative realities to protect a set of core beliefs fundamental to maintain their preferred identities. These models explain stylized facts in domestic and foreign politics, and generate new predictions which I test.

Mots-clés : alternative reality,propaganda,misinformation,populism,conflict,media,welfare program implementation
Projet ERC : MakingTime (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université de Stockholm — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1494433.0 €

Promoting work-life balance has been a focus of recent directives from the European Commission and a source of policy innovation in several countries. Social policies that make time for family and self-care are important tools for building sustainable work, but countries vary considerably in the extent to which such tools are available. Trade union organizations may play an important role for developing statutory care-related leave rights and protections, particularly as women still provide a bulk of family caregiving and now constitute a majority or near-majority of union members in many countries.  This project will use a novel mixed-method design to investigate organized labour’s relationships to national leave policies that grant time-off from work to address care needs, including leave to care for a child, aging parent, or ill spouse or to address self-care needs through sick leave or disability benefits. Quantitative analyses will examine union-policy relationships across rich democracies starting in 1965, and qualitative analyses will examine organized labour’s policy advocacy in Ireland, France and the Netherlands. Analyses of predictors will distinguish between different types of social provisions, consider differences in trade unions and the types of workers they represent, investigate the mechanisms of potential union influence over policy, and compare union-policy relationships across different institutional contexts.  A central ambition is to integrate the interdisciplinary fields of comparative policy analysis and social movement research to advance comparative labour studies and develop new theories of union-policy relationships. The project will additionally develop data infrastructures, offering much-needed longitudinal, comparative data on different types of care leave provisions. Overall, the project will assess the extent to which organized labour can be a partner for developing social policies that promote sustainable work for the future.

Mots-clés : comparative policy analysis,mixed methods,political sociology,social movements,social policy,trade unions
Projet ERC : TheraSonic (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
Entité participante : Université de Heidelberg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499726.0 €

This proposal develops a pioneering microscale ultrasound-based system to enrich extracellular vesicles (EVs) from µL volumes of whole blood and cancer spheroids, targeting early cancer detection and revolutionizing therapeutic approaches.  EVs, nanoscale particles (30-1000 nm) released by mammalian cells, hold potential as biomarkers for cancer detection and as drug delivery vehicles due to their cell-specific cargo and ability to penetrate cell membranes. However, current isolation methods like centrifugation are time-consuming, require large sample volumes, and lack purity and scalability, limiting clinical application, particularly in high-throughput biomarker discovery and therapeutic development.  I propose to overcome these critical barriers through the creation of TheraSonic, a disruptive acoustic force-based microfluidic platform that leverages a novel particle trapping effect in bulk volumes. TheraSonic will enable the unprecedented enrichment of EVs from µL biofluid samples, offering transformative improvements in purity, scalability, and throughput. By integrating spheroid culturing and multi-omics, this platform will reveal insights into cancer heterogeneity.  Moreover, TheraSonic uniquely enables the selective isolation of EV subpopulations based on size, surface markers, and acoustic properties. This unprecedented resolution will uncover highly specific cancer vesicle profiles that current methods fail to detect, leading to the discovery of highly sensitive and specific cancer biomarkers.  The scalable nature of the platform will be harnessed to significantly increase capacity and throughput, providing needed EV material for novel autologous EV therapies. Combined with organ-on-a-chip technologies, it will facilitate the development of individualised cancer treatments on an unmatched scale.  In summary, TheraSonic represents a disruptive innovation that will induce a paradigm shift in EV enrichment, profoundly impacting cancer research and treatment.

Mots-clés : microfluidic,acoustic particle manipulation,extracellular vesicles,cancer,detection,therapy
Projet ERC : Vascular-Rhythm (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université de Heidelberg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499705.0 €

A quiescent, resilient layer of blood vessel-lining endothelial cells (ECs) is vital for maintaining organ function and enabling healthy aging. Much has been learnt in recent years about the mechanisms controlling the resilient EC phenotype. In turn, little is known if and how mechanisms of vascular resilience are affected by environmental rhythmic stimuli (extrinsic (e.g., light-dark, feeding-fasting) or intrinsic (e.g., blood pressure, hematopoiesis)). Performing day/night analyses of mouse liver and lung ECs, we identified distinct organ-specific time-of-the-day dependent transcriptomic programs of resting ECs. These translated functionally into temporal vascular adaptations during the day that critically sustain steady-state tissue health and function. Building on these stage-setting findings, the Vascular-Rhythm project will (i) analyze how ECs sense, adapt, and respond to circadian changes by uncovering rhythmic programs in healthy liver and lung ECs at mRNA, protein, and phospho-protein levels, and (ii) examine how the manipulation of vascular rhythms impacts physiological organ function, organismic aging, and disease initiation. To this end, we will implement a cross-species analytical platform (i.e., comparing nocturnal mice and diurnal pigs), integrate multiomics data with state-of-the-art computational methods, and perform in vitro & in vivo manipulatory assays to discover dynamic gene programs that underlie the homeostatic vascular endothelium and its adaptation to pathologic challenges. Collectively, adding the day/night cycle as a critical, hitherto in the field of vascular research heavily underappreciated research dimension, the Vascular-Rhythm project will fundamentally change the way we study and mechanistically understand blood vessel function. Moreover, the expected groundbreaking discoveries of the project have great potential to identify and validate novel therapeutic vascular vulnerabilities for multiple, circadian rhythm-affected pathologies.

Mots-clés : blood vessels,endothelial cells,capillary endothelium,liver sinusoidal endothelial cells,lung endothelium
Projet ERC : TREAT (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université de Bâle — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UniBasel
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1518750.0 €

Cancer Immunotherapy has revolutionized Clinical Oncology. Yet, CD8 T-cell exhaustion remains a leading cause of treatment failure. This hypofunctional program suppresses anti-tumor CD8 T-cell responses and is reinforced by a stable epigenetic program that prevents exhausted CD8 T-cells (Tex) from reverting to more functional states. Checkpoint inhibitors such as anti-PD-1 can temporally relieve some constraints on TEX and be curative. However, this approach alone does overcome the epigenetic restraints of exhaustion which likely explains the lack of long-term benefits in many patients. Combinatorial approaches are needed to achieve durable protection in more patients. Yet, an incomplete understanding of TEX biology has provided little rationale for relevant therapeutic interventions. Recent identification of an “effector-like” subset of TEX (TEX intermediate; TEXint) that mediates the benefits of PD-1 therapy and partially escapes the epigenetic strains of exhaustion, has brought new therapeutic perspective. Indeed, manipulating key pathways related to TEXint cells formation such as the IL-2/Stat5a axis potentiates TEX responses to PD-1 blockade and partially reprogram these cells towards more durably protective cell states. These findings provide compelling proof-of-concept that targeting key pathways driving Texint cell formation can unlock new strategies to overcome exhaustion and bolster PD-1 therapy. Building on this novel concept, our proposal utilizes advanced murine models alongside molecular engineering, large-scale genetic perturbation tools (CRISPR), and single-cell multiomics to uncover and characterize new regulatory pathways for Texint cell development. Our goal is to unveil new strategies to improve PD-1 therapy and advance next-generation anti-cancer immunotherapies.

Mots-clés : cd8 t cell exhaustion cancer immunotherapy checkpoint blockade combinatorial therapy lymphocytic choriomeningitis virus lcmv murine models cytokines single cell sequencing crispr screen epigenetic reprogramming
Projet ERC : FASTer (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Mental health disorders affect 84 million people across Europe and are associated with an economic burden of €600 billion/year. New evidence from clinical trials suggests that a single treatment with psychedelic compounds, such as psilocybin, can produce a fast (hours) and sustained (months) antidepressant (AD) response. However, many questions still remain about its mechanism of action, due to methodological challenges such as lack of knowledge of the brain cells and circuits where AD effects are taking place and limitations of the behavioral tests used to examine AD activity in rodents. Combining molecular, behavioral and advanced computational tools, FASTer will establish a groundbreaking and automatic behavioral tracking system to deconstruct the behavioral “language” associated with treatment response. In addition, FASTer will identify the brain cells and circuits responsible for the fast-acting and sustained AD effects of psilocybin. This is a move away from the traditional assessment of single behavioral readouts to unconventional group behaviors and endophenotypes in a translationally-relevant context that will cause a paradigm shift and revolutionize the field of behavioral phenotyping. Thanks to my unique know-how in bridging human and pre-clinical psychiatry, and to go beyond the state-of-the-art, I will combine activity-dependent labelling techniques and single-cell methods to identify the genes and brain circuits engaged during psilocybin treatment. To address the multidimensional nature of psychiatric disorders, I will manipulate gene networks related to the AD effects of psilocybin. The ambitious and innovative studies proposed here have the potential to change our understanding of psychiatric disorders, and transform the field of behavioral neuroscience. Ultimately, FASTer holds tremendous promise for translatability of preclinical findings and impacting the development of fast-acting and efficacious treatments for psychiatric disorders.

Mots-clés : psychedelics,psilocybin,antidepressants,treatment response,animal models of stress and anxiety,fast acting antidepressant effects,neurobiological circuits,single cell resolution,translational psychiatry,behavioral tracking systems
Projet ERC : LNC-LIPID (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut Karolinska — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1493925.0 €

Energy is stored in adipocytes as a large uniocular lipid droplet, which can be broken down into fatty acids (FAs) and released into the circulation when needed. This specialised lipid storage and breakdown requires dynamic organisation of metabolic enzymes and cofactors around the large lipid droplet for metabolic homeostasis. In obesity, the adipocyte dysfunctions, resulting in high spontaneous release of FAs. This chronic release and elevation of systemic FAs is a major driver of systemic insulin resistance, type 2 diabetes and other cardiometabolic diseases.  I postulate that long non-coding RNAs (lncRNAs) interact with the metabolic machinery within the adipocyte to organize cell- and stimulation-specific interactomes, channelling substrate flux within the cell. Adipocytes express over 4000 lncRNAs, many of which are unique to humans and this cell type. However, whether these lncRNAs contribute to the adipocyte’s specialised lipid metabolism in health and disease is not understood. This proposed research aims to address this question.  I have already developed key methodologies to study lncRNAs in human adipocytes, including a novel technique called TROOPS that identifies specific lncRNA-interacting proteins. Leveraging an extensive bank of white adipose tissue biopsies from uniquely characterized patients, I will identify disease-regulated lncRNAs and test how they function in human adipocytes. I will use gene editing techniques and lipid/metabolomics analysis to define the role of these lncRNAs in lipid storage and FA release.  Furthermore, I will use protein-lncRNA complex purification combined with advanced microscopy techniques to reveal how lncRNAs can sequester protein complexes into phase-separated organelles and organize adipocyte lipid metabolism. These insights will provide a paradigm shift in understanding how lncRNAs enable the adipocyte to perform specialized functions and new generalizable findings for how lncRNAs contribute to cell function.

Mots-clés : long non coding rna,adipocytes,lipid metabolism,rna protein interactions,cardiometabolic disease