Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PRIME-PD (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 1499921.0 €

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by alpha-synuclein (α-Syn) aggregation. Despite being the fastest-growing neurodegenerative condition in terms of patients affected, there are currently no disease-modifying treatments and diagnosis typically occurs after significant neurodegeneration has already taken place. Intervening in the prodromal phase remains the critical challenge, and gaining a deeper understanding of the underlying pathophysiology is essential. Compelling evidence suggests that α-Syn might aggregate early in the enteric nervous system, spreading to the brain via the vagus nerve and triggering immune cell migration into the brain, where they contribute to disease progression. This project aims to address three key questions: 1) How are peripheral immune cells recruited to the brain in early α-Syn pathology? 2) How do peripheral immune cells interact with brain-resident cells to modulate the spread of α-Syn and neurodegeneration? 3) How do immune profile changes in the blood of high-risk prodromal PD patients relate to disease progression? To answer these questions, I will investigate the entry of peripheral immune cells to the brain using cutting-edge proximity and enzymatic labelling strategies; determine the immune interactome underlying α-Syn pathology and spread by combining α-Syn aggregation assays with in-situ spatial sequencing; and characterize circulating immune cells in prodromal PD patients by employing a humanized engraftment model to link peripheral immune phenotypes to disease progression in patients. By integrating these innovative techniques, this research aims to uncover how peripheral immune cells contribute to the onset and progression of PD, potentially identifying new biomarkers and therapeutic targets for early intervention. Modifying immune cells in the blood to modulate the brain's immune environment represents a major shift in treating PD as a multisystem neuroimmune disorder.

Mots-clés : parkinson s disease,myeloid cells
Projet ERC : EthoFearless (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1497500.0 €

Traumatic experiences generate among the strongest memories that can result in trauma-related disorders. Despite the high prevalence of these disorders, effective treatment options are scarce, calling for a deterministic understanding of the neuronal mechanisms underlying traumatic memory attenuation. For this, rodent studies classically use fear extinction paradigms where aversive experiences are modeled with the exposure to an electrical foot shock. However, the simple nature of this stimulus does not mirror the complexity of traumatic events in humans which is likely to be processed by equally complex networks. Here, I propose to investigate for the first time the neural circuits underlying the extinction of traumatic memories induced by exposure to naturalistic threats, namely, predators and aggressive conspecifics. First, we will compile a comprehensive atlas of brain activity underlying extinction of these ethological traumas and generate network organization models, which will be causally probed by pathway-specific chemogenetic manipulations. Second, we will characterize the functional input-output connectome of ethological extinction centers using a combination of viral tracing, neuronal activity and optogenetically assisted circuit mapping. This set of data will, third, provide the substrate for the study of the neurophysiological and molecular mechanisms underlying efficient extinction of ethological traumas, which will be analyzed by pathway-specific in-vivo Ca2+ imaging, closed-loop optogenetics, ex-vivo electrophysiology and RNA sequencing. Lastly, we will investigate whether impairments at the level of these newly identified networks underlie extinction deficits at the basis of trauma-related disorders. Together, these results will pave the way for the identification of novel therapeutical targets for trauma-related disorders and shed light on how the brain can flexibly update complex memories.

Mots-clés : fear extinction,ptsd,neuroethology,learning and memory
Projet ERC : SleepingAwake (Horizon Europe, appel 2023, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Institut du cerveau — Pays : France — Rôle : Partner
Acronyme de l'entité : ICM
Type d'entité : Recherche
Financement ERC de l'entité : 166066.0 €

What happens in our brains when we get tired? Mental fatigue can occur for diverse reasons, through extended periods of wakefulness or following intense cognitive efforts. In other words, fatigue can be both time and use-dependent. My core hypothesis is that both processes are underpinned by local intrusions of sleep in the awake brain. Sleep and wakefulness are not mutually exclusive states. When animals are sleep deprived, high-amplitude slow waves (SWs), a hallmark of sleep, can be locally observed in awake individuals. These wake SWs have been linked to impaired cognitive performance. I have further shown that these wake SWs can be observed without sleep deprivation when participants perform demanding tasks. These wake SWs predict objective (errors) and subjective (e.g., mind wandering) markers of attentional lapses. However, the underlying mechanisms driving SWs remain unclear; why do they occur? How well do they predict the cognitive consequences associated with fatigue? And can they be externally modulated?  To answer these questions, I will first describe the physiological signatures of wake SWs, from single-neuron to whole-brain activity. Second, I will seek to explain the occurrence of wake SWs by testing their association with the metabolic changes within the brain. Third, whereas wake SWs have been so far associated with adverse behaviors (lapses of attention), I will examine whether wake SWs could also predict positive outcomes, such as creative insights. Finally, I will investigate the possibility of modulating wake SWs and improving cognitive performance.  Through this project, I will build a novel neurophysiological account of fatigue from the ground up by describing what local sleep is, explaining why it occurs, predicting its adaptative purposes, and modulating how frequently it occurs. This ambitious research program will generate critical novel insights into the neural mechanisms underlying the everyday phenomenon of fatigue.

Mots-clés : sleep wakefulness attention mental fatigue mind wandering behavior cognition consciousness neurophysiology metabolism human intracranial recordings electroencephalography magnetic resonance imaging
Projet ERC : StateNeuromod (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut du cerveau — Pays : France — Rôle : Partner
Acronyme de l'entité : ICM
Type d'entité : Recherche
Financement ERC de l'entité : 202500.0 €

Being sleepy, hungry, afraid, or happy impacts our daily experience and defines our behavior and actions. Such internal states are characterized by unique signatures of activity across neural circuits and are actively shaped by neuromodulators, such as dopamine, serotonin, acetylcholine, and norepinephrine, that are released widely throughout the brain to alter the function of target neural circuits. At any moment, distinct combinations of neuromodulators are being released in each brain region. Changes in the neuromodulator balance have a powerful impact on the brain-wide configurations that underlie internal and behavioral states, while most mood disorders are associated with neuromodulator imbalance, and most therapeutic strategies attempt to restore this balance. However, how combinations of neuromodulators define distinct brain configurations and shape internal states remains unknown. The prefrontal cortex and the hippocampus are two interconnected regions, which are essential for cognitive processing and memory. They receive converging neuromodulatory inputs, and synaptic alterations in these regions are critical for learning, while dysfunction of this pathway is involved in most mood disorders. Despite the vital role of these circuits for brain function, little is known about how combinatorial neuromodulation regulates circuit configuration and coordinates information flow between these regions. In this project, we will combine neuromodulator monitoring with large-scale in vivo electrophysiology, optogenetics, and in vivo genome editing to answer the following questions and resolve the contribution of neuromodulators to the organization of neuronal ensembles and information gating in the hippocampus-prefrontal circuit in behaving mice.  1. What is the neuromodulatory landscape across behavioral states? 2. How does state-specific neuromodulation sculpt neuronal dynamics? 3. What are the circuit elements underlying combinatorial neuromodulatory action?

Mots-clés : neuromodulators,prefrontal cortex,hippocampus,sleep,memory consolidation,learning and memory,behavior,dopamine,serotonin,norepinephrine,acetylcholine
Projet ERC : TexTOM (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
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 : 1499694.0 €

Hierarchical structures are signature elements of many biological and technical materials. The orientational distribution of their crystalline constituents (the crystallographic texture) is important for their mechanical properties. Resolving the local structure and orientation spatially while keeping a large field of view is an unsolved problem. I will solve this by introducing texture tomography, a new 3D x-ray diffraction imaging method, the core of the TexTOM project. It will enable to study the enthesis, the biological connection between tendon and bone, and by in-situ deformation and micromechanical modelling, couple its hierarchical structure with the mechanical behaviour. I will use the brilliance gain of 4th generation synchrotrons to develop texture tomography as a tool to image complex crystallographic textures in 3D and overcome the spatial resolution barriers of current approaches. I will develop the reconstruction approach for the crystallographic texture and use it to image the whole enthesis structure with 100nm spatial resolution and, with high energy x-rays, image the enthesis structure during in-situ tensile deformation with µm resolution at several load steps. The unique combination of 3D texture information and loading will allow to build a micromechanical enthesis model. The novelty lies in the structural 3D characterization of the enthesis under deformation. This is enabled by the development of texture tomography to reconstruct the 3D textures, which will be useful for many other scientific problems. I will build an accurate micromechanical enthesis model and this will shed light on the unknown load transfer mechanism in the enthesis on the nano- and crystal level. The flexible, open-source approach of TexTOM will ensure adaptation for new users and scientific problems. 4th generation synchrotrons will propel texture tomography to the forefront of (bio)materials science, revolutionizing our study of crystallographic textures.

Mots-clés : biomaterials characterization,x ray scattering,enthesis,biomechanics,crystallographic texture,micromechanical modelling
Projet ERC : COSMOBEST (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
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 : 1411041.0 €

Cosmology addresses the fundamental questions about our Universe: what is it made of? how does it evolve? Observations suggest that the Universe is undergoing an accelerated expansion---to explain it, cosmologists hypothesize the existence of a mysterious component: dark energy. Despite major recent advances in the field, up to now traditional methods in cosmological analysis have failed to provide a throughout understanding of dark energy. Large-scale surveys, mapping the distribution of billions of galaxies in the Universe, allow us to look back in time and encompass the era when dark energy rises: they are a powerful tool to address our fundamental questions. The next generation of surveys, and in particular the ESA Euclid mission, will map the Universe with high-quality measurements reaching unprecedented precision; they will sample the galaxy distribution in detail also in the emptier regions with fewer galaxies: voids. Void cosmology is in its golden age, and constitutes nowadays an increasingly active sector of galaxy clustering analysis: by measuring void properties we obtain stringent constraints on cosmological parameters. Voids allow to perform a novel and independent analysis of large-scale structure data, bringing us in the regime of COSMOlogy BEyond Standard Techniques. Voids are extremely sensitive to the properties of dark energy and neutrinos, and are a powerful tool to test general relativity in a new regime. COSMOBEST is an ambitious ERC program aiming to exploit voids as a novel and robust tool to shed light on the puzzles of modern cosmology. It capitalizes on the PI's wide experience in building void science in large collaborations, with a strong focus on calibration-free techniques and systematics control. With COSMOBEST I will lead void analysis from modern data, guaranteeing for Europe a worldwide leadership in delivering constraints on dark energy, neutrinos and general relativity from the next generation of surveys.

Mots-clés : cosmic voids,cosmological constraints,neutrinos,large scale surveys
Projet ERC : SensoMotion (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1499639.0 €

An organism’s survival depends on accurately perceiving and interpreting the environment. A significant part of our visual stimulations is however generated by our own actions, rather than external events. For example, the retina can experience similar visual stimulus driven by head-movement, or by a moving object. Therefore, self-motion related information is fundamental to contextualize visual stimuli. In other words, what the eye sees may not be what our brain perceives depending on our actions. In mammals, the vestibular system reports both the motion and orientation of the head. Very little is known about the pathways connecting the vestibular system to visual cortical areas, and how this signal is integrated with external visual stimuli to ultimately impact behaviour. The goal of this project is to unravel the neuronal circuits underlying visual processing during self-motion in mice, thereby providing new insights in sensory processing. To this aim, I will address the following questions: 1) What is the long-range and local connectivity of neurons modulated by head rotation in V1; 2) What are the circuit mechanisms and neuronal computations involved in the integration of self-motion related signals with visual inputs in V1; 3) How do head motion inputs to V1 influence visually-guided actions during behaviour. Achieving these goals relies on a multidisciplinary experimental strategy based on cutting-edge approaches to monitor and control circuit activity with high spatio-temporal resolution in a cell-type specific manner, neuroanatomical tracing, and computational modelling. This experimental strategy combined with my research background in visual and vestibular systems provides a unique opportunity to understand unexplored aspects of sensory processing, at both the cellular and systems levels. Altogether, this project will reveal a novel framework to understand how sensory processing operates during self-motion to guide behaviour.

Mots-clés : sensory system,visual cortex,vestibular system,multisensory integration,mouse behaviour,circuit dissection
Projet ERC : E-BoP (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
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 : 1395888.0 €

The E-BoP project is an innovative study of the legal framework for temporary labour migration in the European Union (EU). While unevenly researched, the subject is hotly debated and in continuous expansion. Temporary labour migration increasingly represents the compromise between calls to "take back control" of borders, and the demands from employers of access to migrant workforce. The legal regulation of this phenomenon is grounded on concepts, such as "temporariness" and "labour market", which are either not defined by the law or in conflict with their socio-economic reality. E-BoP explores these concepts through an empirical legal analysis to address the foundations of the legal framework for temporary labour migration in the EU. In doing so, it covers forms of temporary labour migration which legal doctrine has never analysed together, namely posting of workers, seasonal work, and intra-corporate transfers. The project aims to answer a set of questions concerning this legal framework: what is the implicit definition of "labour market" accepted by legislation and courts, and what are its boundaries? What does the law mean when it classifies certain migrant workers as "temporary"? What would be the legal and socio-economic consequences of conceiving temporary labour migrants as fully integrated in the Member State where they perform their work? The E-BoP project triangulates the results of a systematic analysis of legal documents with quantitative analysis of the phenomena at stake to explore the real world meaning of concepts upon which the legal regulation of temporary labour migration in the EU is construed. As such, the ambition of E-BoP extends beyond the field of labour and social rights, and into other legal disciplines and branches of social sciences. Considering how the legal construction influences employment statistics, leading to the undercounting of temporary labour migrants, the project challenges the societal perception of reality.

Mots-clés : temporary labour migration european union law empirical legal research migration statistics posting of workers seasonal workers
Projet ERC : OralNiche (Horizon Europe, appel 2021, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Universitätsklinikum Würzburg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UKW
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1768583.0 €

The oral epithelium is a unique tissue with a high degree of structural heterogeneity and distinct microenvironments (niches). However, the molecular mechanisms underlying the site-specific proliferation and differentiation of oral epithelial stem cells (OESCs) remain poorly understood. Oral squamous cell carcinoma (OSCC), one of the most common oral cancers, is a heterogeneous cancer type. Occurrences of metastatic lesions and treatment response differ from oral site to site, indicating a causal link to the heterogeneous nature of distinct OESC pools. In the OralNiche project, we will for the first time systematically and comprehensively characterise the OESC pools, dissect key mechanisms underlying oral epithelial site-specificity and define their contribution to OSCC heterogeneity. To achieve this, we will combine novel mouse models and patient material with cutting-edge methodology, including whole mount imaging, single-cell sequencing and organoids. Initially, we will profile the proliferative activities of OESCs and explore how stemness is regulated within defined niches in homeostasis, OSCC and chemotherapy-induced mucositis. Subsequently, we will functionally assess cellular cues that modulate stemness in the oral epithelia and generate a comprehensive single-cell atlas of OESCs and their cellular niches. Lastly, using OSCC patient material, we will validate key observations to define potential new biomarkers and therapeutic targets. In summary, this multidisciplinary approach will reveal how the distinct OESC pools maintain homeostasis, and how they respond to challenges, such as mucositis and OSCC. OralNiche will deliver new knowledge on the impact of tissue site-specificity on tumour heterogeneity and therapy response, which will have significant implications for OSCC patients. Moreover, the knowledge gained and the technological advances proposed will be applicable to other tissues and tumour types and thus provide a model approach in cancer research.

Mots-clés : oral mucosa,oral cancer,tissue stem cells,lineage tracing,organoids,single cell sequencing