Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : DICACO (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Université d'Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1740452.0 €

DICACO analyses causes, consequences, and welfare effects of diversification, once equilibrium effects that affect investor welfare and side effects that affect consumers and taxpayers are considered. The analysis informs the question: Is cheap diversification good for society?  Sub-projects investigate (i) Theory: whether benefits of diversification that accrue to individual investors viewed in isolation also benefit investors in equilibrium, once effects on asset prices are considered; (ii) Empirics: to which extent diversification motives drive “common ownership” of product market competitors; (iii) Theory and empirics: whether bidding behavior in government procurement auctions depends on whether bidders are owned by diversified investors, how much taxpayer money is inefficiently transferred to shareholders as a result, and how procurement auctions could be redesigned to re-claim efficiency losses caused by diversified ownership of bidders; (iv) Theory: how predictions on portfolio choice, equilibrium ownership, asset prices, firm behavior, and product prices depend on jointly endogenizing all these variables, and how this equilibrium depends on the implementation of policy proposals that seek to restrict investor diversification.  We use tools from general equilibrium theory and numerical computer simulations in (i) & (iv); machine learning and reduced-form econometrics in (ii); auction theory and structural estimation in (iii).  The project develops new methods to solve equilibrium asset pricing models and for auction theory. The uniquely comprehensive dataset on corporate ownership will be open sourced for academic research worldwide. Because of the potential to shift beliefs, the provision of new tools for academic research, and because policy makers might erase trillions of Euros of economic gains by enacting the wrong policies, overall, the risks of the project are justified by the high gains for both researchers and policymakers.

Mots-clés : diversification,competition,governance,common ownership
Projet ERC : GLYCOCIRC (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université de Vilnius — Pays : Lituanie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Neuronal glycocalyx has been recently recognized as an active agent that contributes to neuronal synapse formation, neuron excitability as well as neuron-autonomous and microglia-dependent brain network remodelling. In particular, the glycan-terminating sialic acids, which often dominate the ends of the chains of glycoproteins and glycolipids on neuronal surface, are required for appropriate brain development and function. Interestingly, almost a fifth of sialic acid biology genes have human-specific changes and aberrant neuronal sialylation and desialylation are implicated in different neurodevelopmental and neuropsychiatric conditions. Thus, I hypothesize than neuronal glycocalyx and specifically its component sialic acid in particular have a critical role in the formation of unique human brain. Despite its recognized importance, there is still a lack of mechanistic understanding filling the knowledge gap how synapses are shaped by the dynamics of the glycocalyx. Therefore, here I propose to merge my expertise in biochemistry and neuroscience to tackle this challenging area of research to further our knowledge of brain sialome through evolutionary approach. We will use in vitro, ex vivo and in vivo models from humans, non-human primates and mouse that can be modified at genetic level for selective labelling and modification of neuronal cells and will combine it with advanced microscopy techniques as well as synaptic-level molecular analysis. We will demonstrate how the glycocalyx and sialic acid act as a defining factor for neural circuitry formation and refinement in developing brain, in particular through the interaction of neurons and their synapses with brain immune cells – microglia. Our results will advance our understanding of fundamental contribution of the glycocalyx to brain physiology and pathology with the translatability to human conditions, thus paving potential ways to develop treatment for brain network disorders.

Mots-clés : glycobiology,ipsc,metabolic labelling,crispr,viral vectors,organotypic cultures
Projet ERC : antiCAFing (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1999826.0 €

Refractory tumors and emergence of drug resistance are the most important challenges in cancer therapeutics. The non-cancerous determinants of therapeutic response and particularly the role of the tumor microenvironment (TME) in resistance are poorly understood. I previously described the crucial role of cancer-associated fibroblasts (CAFs) in key tumorigenic processes, including matrix remodeling, cancer cell invasion and growth. Importantly, these aggressive CAF phenotypes are controlled by mechanical reprogramming and mechanotransduction pathways. Within therapeutic resistance contexts, I hypothesize that preexistent and therapy-induced aberrant activation of mechanotransduction signaling in CAFs leads to the generation of refractory TMEs affecting cancer cell signaling and the behavior of accessory stromal cells such as endothelial and immune cells. As a result, tumors will present: (i) abnormal vasculature associated with reduced drug perfusion and chemotherapy efficacy; (ii) increased production of pro-survival signals affecting targeted therapy; and (iii) inactivation of cytolytic T cells and reduced responses to immunotherapy. I propose that CAF-based biomarkers will improve our capacity to identify patients most likely to respond to these therapeutics. In addition, targeting mechanotransduction in CAFs will significantly increase efficacy in non-responders. Focusing in colorectal cancer, I will use patient-derived CAFs as a tractable system and organ-on-chip, in vitro and preclinical models of CAF-mediated resistance, and combinatorial chemistry to systematically elucidate the molecular and biological features conferring CAFs their privileged therapy-resistance properties. This will illuminate novel and general mechanisms whereby TME characteristics influence tumorigenesis, and inform the development of refined biomarkers to stratify patients and next generation combinatorial therapies (including anti-CAF therapies) with reduced risk of recurrence.

Mots-clés : tumor microenvironment,cancer associated fibroblasts,mechanotransduction
Projet ERC : 3D-REVOLUTION (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1998217.5 €

Vertebrate genomes are organized in 3D regulatory landscapes that control pleiotropic gene expression. Within them, transcription emerges from a precise interplay between genes, regulatory elements and 3D chromatin organization. We and others have shown how mutations in these regulatory layers can modulate phenotypes. However, how 3D regulatory landscapes shape the evolutionary history of developmental programs is still largely unexplored.  Our limited capability to read, interpret and modify genomes has constrained our knowledge on how gene regulation evolves. However, recent advances in long-range sequencing, single-cell, chromatin interaction and genome editing methods offer novel tools to link genomic variation and phenotypes. Here, I will combine these methods to investigate how changes in 3D regulatory landscapes contribute to refine the function of developmental programs. As a testbed, I will study gonadal sex determination, an essential process for species perpetuation but characterized by a remarkable evolutionary plasticity.  We will use single-cell transcriptomics across tetrapod clades to unravel the core and variable transcriptional network of sex determination. Single-cell epigenomics and novel chromatin interaction methods will reconstruct 3D regulatory landscapes and infer sources of regulatory variation. With phylogenomic comparative strategies, we will estimate the contribution of different types of mutations to different sex determination programmes, as well as the impact of whole genome duplications. Finally, we will develop innovative transgenic methods for inter-species replacement of 3D regulatory landscapes, using this technology to activate early estrogen synthesis in mouse. 3D-REVOLUTION will provide ground-breaking insights on the evolution of gene regulation. This will improve our understanding of the genomic sources and underlying mechanisms of phenotypical variation, which are relevant for developmental and evolutionary genetics.

Mots-clés : 3d chromatin organization
Projet ERC : PLAS-FIGHTER (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1999573.0 €

The discovery of antibiotics revolutionised the fight against infectious diseases and paved the way for modern medicine. However, widespread use of antibiotics has driven rampant evolution of antimicrobial resistance (AMR) in bacteria. The main route for AMR acquisition in clinically important bacteria is the horizontal transfer of plasmids (conjugation-competent mobile genetic elements) carrying resistance genes. AMR plasmids allow bacteria to survive antibiotics, but they also entail physiological alterations in the host cell. Recent results from my group and others reveal that AMR plasmids (i) produce a shared set of physiological alterations in the bacterial host and (ii) induce changes in host antibiotic susceptibility profiles. The goal of PLAS-FIGHTER is to exploit plasmid-induced physiological effects in bacteria to develop new ecology- and evolution-informed strategies against plasmid-mediated AMR. First, we will use genome-wide CRISPRi screening technology to dissect the molecular basis and functional consequences of plasmid-induced physiological effects in clinical bacteria at an unprecedented level of resolution, revealing new specific targets in AMR plasmid-carrying cells. Second, we will perform high-throughput susceptibility assays, using inhibitors of the targets revealed in the first objective and a wide range of antibiotics in a collection of paired isogenic plasmid-carrying & plasmid-free bacterial strains of the highest clinical relevance. Crucially, we will perform experiments and test candidate treatments in a gradient of increasing ecological complexity, in terms both of community composition (from monocultures to human gut communities) and habitat structure (from in vitro lab cultures to the mouse gut). In PLAS-FIGHTER, I will build on my established expertise and pioneering results to develop a novel, multidisciplinary, ground-breaking project that will open up new research avenues towards ecology- and evolution-informed anti-AMR strategies.

Mots-clés : mobile genetic elements,plasmid biology
Projet ERC : OPIMPOL (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 865647.66 €

International migration affects the lives of millions, both at origin and at destination. It is known to generate aggregate benefits for destination countries even though labor market prospects of some natives may be worsened. Depending on the type of migrants, it can also benefit or harm origin countries. The design of immigration policies that maximize benefits, foster immigrant integration, and compensate potential losers is key for overall welfare. This project develops a systematic framework to design optimal immigration policies and provides a comprehensive evaluation of such policies’ welfare effects.  We build our analysis focusing on five policy goals: i) redistribution policies that transfer some of the benefits from winners to losers; ii) optimal methods to assign immigrant visas; iii) preferential tax schemes for high-earning foreigners that encourage positive self-selection in skills; iv) selective immigration policies that are not detrimental, or even foster, origin countries’ economic development; and v) spatial allocation policies for immigrants that incentivize the accumulation of skills and assimilation.  We develop and estimate a dynamic equilibrium framework to achieve these goals. The framework features, among others: human capital and labor supply decisions both at origin and destination; endogenous migration and return migration decisions; multiple sources of observed and unobserved heterogeneity; a worldwide general equilibrium that accounts for aggregate and idiosyncratic uncertainty; and the presence of knowledge spillovers and externalities from using skilled labor and capital equipment in production. The richness of the model and the variety of datasets used in estimation are unprecedented, which poses important methodological challenges. We develop novel estimation algorithms that allow us to address these challenges. We use the estimated model to design and evaluate optimal policies through simulations.

Mots-clés : immigration,migration decisions,optimal policy,labor markets,structural microeconometrics,equilibrium,dynamic discrete choice,taxation,ccp estimation
Projet ERC : MIMIR (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 2543230.0 €

Plant-beneficial microbes can modulate the plant immune system enhancing plant resistance to insect pests. This phenomenon, known as Microbe-Induced plant Resistance (MIR) has emerged as a sustainable pest control strategy. Strikingly, my latest results indicate that MIR-immune responses elicited in plants cascade upwards leaving a molecular imprint in surviving insect herbivores (a MIR-imprint). This suggests that MIR-triggered responses in plants could ‘travel’ beyond the plant and be incorporated into plant-associated communities. However, inclusion of the effects of MIR-elicited responses across different members of the trophic chain, from plants to herbivores, their natural enemies, and the soil microbiome, has been neglected in MIR research. The overall goal of MIMIR is to unravel how, and to what extent, MIR immune responses triggered in plants are transduced and incorporated in plant-associated communities. MIMIR will use a multidisciplinary approach combining multi-omics high-throughput techniques, computational biology, functional genomics, and mesocosm experiments to address three main challenges: (1) Disentangling molecular regulation of the onset and functioning of the MIR-imprint in insect herbivores; (2) Unravelling how and to what extent the MIR-imprint crosses to the third trophic level (natural enemies), and its impact on species interactions; and (3) Deciphering how and to what extent MIR imprints the rhizosphere microbiome generating a soil MIR-memory with impacts on aboveground insects. MIMIR will foster a detailed understanding of how MIR-triggered responses ‘travel’ from the plant to plant-associated communities, and to what extent they are incorporated into the agroecosystem, launching the field into new and exciting directions. In a broader context, MIMIR will provide multiple crucial insights into the fundamental question of how species interact in complex systems, a question of high relevance for the global challenge of food security.

Mots-clés : beneficial microbes biological pest control microbe induced resistance multitrophic interactions plant microbe insect interactions
Projet ERC : TransNeuroFate (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Centre européen de recherche en biologie et en médecine — Pays : France — Rôle : Partner
Acronyme de l'entité : CERBM
Type d'entité : Recherche
Financement ERC de l'entité : 780000.0 €

The cerebral cortex is a central structure of the mammalian brain, characterized by a remarkable diversity of neuronal types. Understanding the origin of the extraordinary neuronal diversity is fundamental to understand how cortical architecture and functions emerge during development and remains a critical challenge in cellular and molecular neurobiology. While the efforts have been focused on transcriptional control, evidence for regulation at the translational level is emerging. I hypothesize that translational control, albeit overlooked, acts in a combinatorial fashion with transcriptional induction to regulate gene expression programs during cortical patterning. I have demonstrated an intimate functional link between cortical development and pools of mature transfer RNA (tRNAs), the major determinant of translation. I, therefore, propose to address how translational control, through the modulation of the availability of mature translationally competent tRNAs, fine-tunes gene expression programs during lineage progression, thereby regulating neuronal diversity. Studying this yet unexplored question should unravel a hitherto unrecognized level of neuronal fate identity determination in the cerebral cortex. We will combine ribosome profiling, mRNA and tRNA deep sequencing, screening of genetic perturbation and gene manipulation in vivo in the mouse embryonic cortex to i) uncover the specific translational programs that influence neuronal lineages progression; ii) determine how tRNA repertoires (both at the transcriptional and post-transcriptional levels) are shaped to meet the specific translational needs of different cell types during corticogenesis and iii) validate the functional importance of fluctuation in mature tRNA content during cortical development. This project should bring conceptual advances in the understanding of brain development mechanisms that could be instrumental to interpret the pathological mechanisms of neurodevelopmental disorders.

Mots-clés : cortical neurogenesis,neuronal diversity,transcriptional priming,translational control,trnas
Projet ERC : DIVERSE (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Université libre de Berlin — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1993270.0 €

New observational capabilities with the JWST and ARIEL space telescopes will strongly advance our ability to characterize exoplanetary atmospheres. While the community focusses mainly on biosignatures, in DIVERSE I will search for signatures of geophysical factors that influence habitability, specifically the diversity of planetary redox states. The redox state is of major importance for habitability, since reducing conditions favour prebiotic chemistry for life as we know it. Atmospheres of rocky planets are typically divided into two distinct classes – H2/He-dominated (reduced) atmospheres of primordial origin – here denoted as Class I planets – or secondary (more oxidized) atmospheres of volcanic origin – here named Class II planets. In the Solar System, observations are limited to old, evolved atmospheres that became oxidized over time and do not allow to directly constrain the planets’ interior redox states. Furthermore, detection of reduced species such as CO or CH4 does not unambiguously link back to the interior redox state.  In contrast, if we were able to detect H2-dominated atmospheres lacking He – here called Class X planets – the most likely explanation would be strongly reduced degassing from the magma ocean or subsequent volcanism. Distinguishing Class I and X planets would truly allow to constrain the planetary redox state and indicate how it depends on observables such as stellar composition or planetary mass. Estimates on the distribution and observability of Class X planets are yet missing but became recently possible. DIVERSE will build strong predictive, theoretical models, linking the interior evolution including core formation with atmospheric abundance and erosion models including the observability potential, to determine the diverse evolution pathways of reducing atmospheres of primary, secondary or hybrid origin. I will thus address whether (and for which planet classes) the atmosphere could indeed serve as a window into the interior.

Mots-clés : exoplanet formation core differentiation redox state magma ocean volcanic outgassing atmosphere
Projet ERC : SUPERLAND (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Université d'Uppsala — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999433.0 €

Superconductivity is a truly quantum mechanical phenomenon, strongly dependent on the zero-energy density of states (DOS). This project aims to create and enhance superconductivity using nanoscale inhomogeneity to produce large DOS peaks at zero energy, thereby creating an entirely new, spatial and figurative, landscape for superconductivity. One recent example is twisted bilayer graphene, an all-carbon material that becomes superconducting due to a moiré structure producing large zero-energy DOS peaks. In this project we will establish superconductivity driven entirely by nanoscale inhomogeneity generating zero-energy DOS peaks, including in moiré structures. We will also use zero-energy DOS peaks to create a superconducting phase crystal in many different superconductors, generalizing findings from high-temperature cuprate superconductor surfaces. In the project we will continue to develop our state-of-the-art computational tools to self-consistently study superconductivity in large inhomogeneous systems at the atomistic level.

Mots-clés : superconductivity,disorder,moire structures,surface states