Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PRECHRON (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université de Groningue — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498531.0 €

Working memory (WM) is a crucial part of human cognition, yet how the brain maintains and organizes different pieces of information is unresolved. I propose that spike-field coupling (SFC), which is the exact moment in time when a neuron spikes in relation to the surrounding neural oscillation (field), is what organizes WM content. Accordingly, different WM items or features are maintained through SFC at different phases of prefrontal brain oscillations. Metaphorically, the prefrontal oscillation represents a chest, where each phase is a drawer. Neural spiking opens the drawer, allowing specific data to be maintained separately from other data. While this idea is supported by animal research, due to the invasive nature of used methods, evidence in humans is missing. Novel technology, which combines non-invasive neuromodulation (TMS) and physiological recordings (EEG) in a closed-loop system, now enables phase-specific SFC to be non-invasively induced in humans.  By leveraging and further developing closed-loop TMS-EEG, PRECHRON will test the idea that the interaction between spiking and oscillation in the prefrontal cortex is the mechanism for separating maintained WM information. Based on previous studies, the focus will be on theta (4-7 Hz) oscillations. PRECHRON will test four independent, non-mutually-exclusive hypotheses: 1. SFC at a resting state (no task) predicts overall WM performance; 2. Phase-specific SFC during a WM task organizes WM of different domains (e.g., verbal and spatial); 3. Phase-specific SFC during a sequential WM task organizes the temporal order of WM items; 4. Phase-specific SFC during a visuospatial WM task organizes the location of WM items. Thus, PRECHRON will explore, for the first time, exactly how the prefrontal cortex maintains various types of WM information. The results will enhance our knowledge of neurophysiological processes in human cognition and open the door to understanding cognitive deficits in brain-related disorders.

Mots-clés : working memory spike field coupling oscillations transcranial magnetic stimulation electroencephalography
Projet ERC : TrickE3 (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut de recherche en biomédecine — Pays : Espagne — Rôle : PI
Acronyme de l'entité : IRB
Type d'entité : Recherche
Financement ERC de l'entité : 1499625.0 €

Classical drug design relies mostly on the availability of accessible pockets to block specific protein activities. Despite tremendous progress, more than 80% of all human proteins remain beyond the reach of traditional inhibitor-centric approaches. Chemical ablation of protein abundance using bivalent degraders (PROTACs) moves away from an occupancy-driven (inhibition) to an event-driven (binding) pharmacology. However, their design is intrinsically limited to targets that are ligandable via chemical probes. To tackle current unmet clinical problems, we need transformative paradigms. Fortuitous discoveries have illustrated the immense potential of monovalent degraders. These molecules induce the degradation of target proteins by molecular gluing to E3 ubiquitin ligases or by prompting their destabilization. They have desirable drug-like properties, proven capacity to induce the degradation of proteins otherwise deemed undruggable, and they are already a clinical reality. However, their discovery has been driven by serendipity, thereby hampering their realization as a generalizable drug solution. TrickE3 seeks to establish the foundations for the systematic development of monovalent degraders. To this end, we will develop innovative methodologies to detect and predict drug-induced changes in the interactome/activity of E3s at scale. As proof of principle, we will focus on the chemical rewiring of E3s expressed in pancreatic ductal adenocarcinoma (PDAC) due to the imperative need for treatments. We intend to prospectively identify monovalent degraders (i) of specific vulnerabilities, and (ii) to unlock new PDAC targets. At the interface of chemical biology and cancer research, TrickE3 will be an instrumental resource to broaden drug discovery efforts, probe disease-relevant vulnerabilities and, overall, widen the targetable space of the human proteome. We hope to empower other disciplines to chemically explore, without limits, the degradation of relevant targets.

Mots-clés : monovalent degraders,novel therapeutic approaches,targeted protein degradation,e3 ubiquitin ligases,targeting the undruggable,unmet clinical needs,pancreatic ductal adenocarcinoma
Projet ERC : PersonalRiskProfile (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1499891.0 €

Serious mental illness (SMI) has devastating effects. The key clinical challenge is to identify individuals at increased risk for SMI for personalized prevention. However, the specialized clinical teams aiming to identify at-risk individuals face major challenges: risk assessment is suboptimal as only clinical characteristics are considered, and only psychosis is considered ignoring risk for SMI disorders without psychosis.  Genetics has great potential to significantly improve identification of at-risk individuals. However, the major current problem preventing clinical implementation is that no appropriate method exists to accurately assess genetic risk of multiple SMI disorders. In this ambitious PersonalRiskProfile-project, my team and I will develop this much-needed method and software: the personalized genetic risk profile (PGRP)-method. PGRP will use advanced genetic techniques to simultaneously compute the risk for multiple SMI disorders that regularly but not always include psychosis: schizophrenia, bipolar disorder and major depressive disorder. Specifically, we aim to Optimize Prediction & Generalize to Diverse Ancestries (Aim 1), by including polygenic risk scores for SMI-disorders and auxiliary helper-traits, including rare genetic variants, and accounting for time-since-risk-assessment effects and family information; and to Validate & Prepare for Implementation (Aim 2), by validating PGRP in clinical cohorts, determining the best strategy to integrate PGRP with clinical risk assessment, investigating the stakeholders’ perspective, and developing an Online Dashboard to intuitively present PGRP-results. This ambitious interdisciplinary project provides a key step towards personalized prevention using genetics. I am uniquely qualified to lead, having established myself as international expert in statistical genetics through development of high-impact innovative methods and prestigious fellowships, combined with my clinical expertise as psychiatrist.
Projet ERC : LEAP (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1401306.5 €

How we consciously experience the world remains a mystery in science. To tackle this problem, scientific works on perceptual consciousness contrast brain activity when participants consciously perceive a stimulus versus when they are unaware of it. To report stimulus awareness, participants need to make decisions. However, the extent to which the well-studied mechanisms of decision-making apply to consciousness is unclear. One possible reason is that standard neuroimaging methods lack the sensitivity to observe whether the mechanisms of decision-making also operate in the absence of task relevance, as when participants become conscious of a stimulus irrespective of any task. In this project, I will test the hypothesis that a mechanism of decision-making –evidence accumulation– explains how perceptual consciousness unfolds over time. First, I will develop a computational model of a latent evidence accumulation process (LEAP) and test it on behavioral measures of phenomenal aspects of perceptual experience: its duration and intensity. Second, I will search for single neuron activity in humans that instantiates evidence accumulation and test whether it also determines these phenomenal aspects of perceptual experience. Third, I will stimulate the corresponding brain regions to disentangle their causal role in either solely triggering perceptual experience or shaping it. Last, I will use the LEAP model to explain hallucinatory-like experiences in patients with Parkinson's disease and test whether deep-brain stimulation affects only decision-making –as previously shown– or also perceptual experience. By combining computational modeling and cutting-edge electrophysiology, the LEAP project will provide unique mechanistic insights on how neuronal activity determines perceptual experience and guides its temporal dynamics. It will also provide a tool to better understand hallucinations, which remain today a major debilitating symptom in numerous psychiatric disorders.

Mots-clés : consciousness,perception,human,electrophysiology,neuron,model
Projet ERC : MACHETE (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : CERCA Institution — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CERCA;I-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 1604375.0 €

Cancers arise through genetic and epigenetic alterations that drive the transformation of single cells into malignant tumors. Among genetic changes, copy number alterations (CNAs) are recurrent chromosomal events that increase or decrease the dosage of specific regions of DNA, can affect up to 30% of a cancer cell genome, and are associated with poor clinical outcomes. Despite their pervasiveness, the functional effects of specific CNAs on cancer phenotypes remain largely unknown, as current approaches cannot faithfully recapitulate the unique properties of these chromosomal alterations. Indeed, CNAs can uniquely affect the expression of hundreds of linked genes and change DNA topology, which in turn can promote intra-tumor heterogeneity as illustrated by random segregation of oncogenes in extra chromosomal DNA (ecDNA). In order to study the functional role of CNAs in cancer, this proposal employs MACHETE, a novel genome engineering toolkit that enables the generation of megabase-sized deletions, gains, and oncogene amplification in ecDNA. Using pancreatic ductal adenocarcinoma (PDAC) as a disease model, we will engineer the major CNAs in this lethal tumor to dissect their role in immune evasion, metastasis, and response to therapy. Additionally, through sequential engineering we will study whether the order of CNA acquisition leads to divergent or convergent phenotypes, a highly relevant yet unexplored aspect of cancer biology. Overall, by combining the MACHETE genome engineering platform with in vivo cancer models and molecular approaches, this proposal will begin to systematically dissect the function of recurrent CNAs in PDAC, with direct implications for therapy. Importantly, the methods and conceptual framework of this proposal are broadly applicable to other cancers and diseases characterized by similar chromosomal alterations, where understanding their underlying biology may lead to a new class of CNA-based clinical targets.

Mots-clés : cancer genetics copy number alterations genomic deletions genomic gains extra chromosomal dna cancer genome evolution
Projet ERC : REGENECREST (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1497500.0 €

Cell differentiation progresses via a continuous lineage restriction process where cell potential is reduced as the embryo develops. Pluripotent embryonic cells can beget all somatic cell types, but this capacity is rapidly restricted during the formation of the three germ layers, each giving rise to distinct cell types. Uniquely among vertebrates, a stem cell-like population arising in the embryo rostral part ? called cranial neural crest cells (CNCC) ? challenges this paradigm. CNCC not only give rise to ectoderm derivatives, such as neurons and glia, but also to cell types canonically associated with the mesoderm such as bone and cartilage of the face. During my postdoctoral training I demonstrated that murine CNCC naturally reverse cell differentiation to return into a pluripotent state during development. In addition, I showed pre-migratory CNCC carry positional information reflective of their spatial origin in the neuroepithelium. However, this identity is subsequently erased with migratory CNCC forming a transcriptionally homogenous population, which later re-diversifies as CNCC undergo commitment events. In my research proposal, using single-cell transcriptomics and genomics assays I seek to uncover and characterize gene regulatory networks and chromatin rearrangements regulating the reemergence of pluripotency programs within CNCC and the underlying reprograming of cellular identity. CNCC represent a unique model to study the molecular mechanisms governing cell-intrinsic behavior but also the role of the niche, which may influence the sequence of events by cell-cell interactions during craniofacial ontogeny. The interdisciplinary scope of experimental strategies included in this proposal will help understand how these fundamental processes are regulated and might result in novel strategies to stimulate craniofacial tissue repair, as cell dedifferentiation and reconfiguration of positional identity are two essential milestones for endogenous regeneration.

Mots-clés : pluripotency,cell plasticity
Projet ERC : STMoire (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Institute of Photonic Sciences — Pays : Espagne — Rôle : PI
Acronyme de l'entité : ICFO
Type d'entité : Recherche
Financement ERC de l'entité : 2444163.0 €

Moiré materials are a unique platform to study novel quantum phenomena. Their exotic properties, resulting from electron interactions, present an opportunity to develop novel fundamental knowledge and innovative technologies. Moiré superlattices arise when atomically thin layers are slightly misaligned. Their hybridization creates flat bands – states where electrons have zero kinetic energy. As a consequence, interactions between them dominate the physics. This means that the material’s properties cannot be understood in terms of the individual electrons but as a collective phase that all belong to. Superconductivity, correlated insulators and topology have been reported, but their nature and interplay remain unknown. A great limitation in the field is the lack of microscopic information and the disparity in experimental results that arise from sample inhomogeneity. In this context, local probes are key to unravel the true ground state. STMoiré aims to understand the quantum phases that emerge in magic-angle twisted graphene. STMoiré will explore the unconventional superconducting mechanism and the interplay between correlated phases through an experimental strategy that independently and complementary addresses these open questions. I will do so by means of low-temperature Scanning Tunneling Microscopy and Spectroscopy. STMoiré will benefit from my unique expertise in moiré physics and device fabrication to develop an experimental approach beyond the state-of-the-art that combines high-quality sample engineering, ultra-high-energy resolution and atomically-resolved measurements. The goal is to explore the nature of superconductivity and develop a holistic understanding of the phase diagram. This will significantly contribute to condensed matter physics by deepening our knowledge of superconductivity in a new correlated material, expanding the current understanding, and potentially revealing a novel form of superconductivity.

Mots-clés : stm,moir,twisted graphene,superconductivity,flat bands
Projet ERC : DECIPHER (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Centro de Regulación Genómica — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG
Type d'entité : Recherche
Financement ERC de l'entité : 1799999.0 €

Human cells engineered in vitro have revolutionized our ability to model human biology and diseases, offering exciting opportunities for therapeutic screening and intervention. However, single-cell transcriptomics (scRNA-seq) reveals that engineered cells often remain heterogeneous, immature, and dissimilar to primary counterparts. Precise cell engineering remains challenging without systematic interrogation of gene regulatory networks (GRNs) that establish cell identity. Here, we propose to engineer precise cell fates and states by coupling GRN decoding, perturbation screening, and single-cell technologies. Our vision is to decode GRNs that shape cell identities in fate specification, multicellular communication, and maturation, and use this insight to 1) engineer precise cell subtypes, 2) reconstruct niche-specific signatures, and 3) accelerate maturation. Using human induced pluripotent stem cell (iPSC)-derived neural cells, we will first couple combinatorial transcription factor screening with scRNA-seq to directly induce iPSCs into specific neuron subtypes guided by primary neuron GRNs. Second, we will program glial cell subtypes and reconstruct multi-cellular niche with neurons, analyze how niche cross-talk impacts cell fates and states, and use emerged GRNs to engineer niche-specific signatures. Finally, we will decode dynamic GRNs during neural maturation and screen for determinants to accelerate maturation. DECIPHER aims to dissect the causal links between GRNs and cell identities, offering mechanistic insights into drivers of cell identity changes with the ambitious goals to engineer precise and mature cell subtypes for disease modeling, cell therapy, and regenerative medicine. Our approach holds great potential to study diverse cell fate and state transition events, such as development, reprogramming, regeneration, and cancer. The perturbation atlas generated here will empower AI-driven predictive modelling to guide future cell engineering.

Mots-clés : cell fate and state engineering single cell multiomics induced neurons ipsc derived models gene regulatory network perturbation screening
Projet ERC : ATHENA (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Centro de Regulación Genómica — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG
Type d'entité : Recherche
Financement ERC de l'entité : 1498680.0 €

Proteins offer an exciting path to address a multitude of biotechnological challenges. Capable of working under non-toxic, mild conditions and performing a myriad of functions, their controllable design has been sought-after for decades. However, to gain a technological advantage in a world with pressing demands in sustainability and healthcare, we must accelerate the development of custom-tailored, proficient proteins. In this proposal, we will develop an intelligent system capable of efficiently engineering functional proteins tailored to user-defined specifications.  Artificial Intelligence (AI) advancements are promoting a fresh wave of enthusiasm across many fields, providing solutions to problems that escape human intuition. Recently, protein language models (pLMs) are showing unprecedented performance in generating novel, efficient proteins. We have trained three advanced pLMs, demonstrating promising preliminary results in experimental settings. In this proposal, we will train an agent that will learn from combined sequence, structural, functional, and dynamic data to perform multiple protein engineering tasks. The agent will iteratively improve from experimental feedback using Reinforcement Learning, and explainable AI will allow us to ‘open the black box’ and understand its decision process. A vital component of this work will be its rigorous experimental validation, progressing through increasingly challenging tasks with biotechnological applications. This project will deliver an intelligent agent with continuous learning capabilities, accessible through user-friendly interfaces, empowering researchers worldwide with an easy-to-use tool to design custom-tailored proteins. In addition, by incorporating explainability, it will offer a novel angle to understanding complex sequence-to-function relationships. Lastly, comprehensive experimental validation will assess the reliability and applicability of these novel approaches in real-world contexts.

Mots-clés : artificial intelligence,intelligent systems,protein design,enzyme engineering,reinforcement learning,explainable artificial intelligence
Projet ERC : FATE (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Leibniz-Gemeinschaft — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WLG
Type d'entité : Recherche
Financement ERC de l'entité : 1499750.0 €

The root cortex is a primary ground tissue of the root organ and plays an important and adaptive role in plant growth and function. Root cortical parenchyma, thin-walled cells in the cortex, have great potential to change both in structure and function during plant development, even after cell differentiation. Root cortical cells can have many different post-differentiation fates that form different cortical tissues (e.g. aerenchyma, exodermis) in succession, or even simultaneously through the deposition or degradation of lignin and suberin and programmed cell death. The formation of these different cortical tissues have the potential to influence stress adaptation and plant performance, for example by altering the radial movement of water and solutes, the metabolic efficiency required for nutrient exploitation, and the synthesis and deposition of exudates.  I will investigate the developmental transition of cortical cells into different cell fates and the extent to which root cortical parenchyma have different cell fate trajectories to form simultaneous or successive cortical tissues. I will discover the potential of tissues for synergistic interactions to capture soil resources and modify of rhizosphere properties, and the genes that control these processes at a single-cell resolution to discover when and where signals occur in the cortex. I will use a combination of breakthrough technologies and interdisciplinary expertise including state-of-the-art imaging, analytical chemistry, microbial ecology, and cutting-edge molecular biology methods to tackle the fundamental questions of how and why root cortical parenchyma have different post-differentiation cell fates.  FATE will enable us to engineer crop roots to optimize soil foraging and resource capture. The payoffs of this project will be significant for European agriculture, as nutrient limitation is a primary constraint on crop growth and will become an increasing challenge due to climate change.