Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : GEMREX (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University College de Londres — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Biallelic repeat expansion in RFC1, an essential gene involved in DNA replication and repair, are a leading cause of ataxia and neuropathy in the adult population. Nonetheless, the exact mechanism linking RFC1 repeat expansion and neurodegeneration remains elusive. The prevailing hypothesis is that the repeat may lead to a partial loss of function of RFC1, by affecting expression of neuron specific RFC1 isoforms or by impairing its fine regulation in terminally differentiated neurons, including sensory neurons and Purkinje cells.  The objective of proposal is to leverage state-of the-art genomic medicine methods, including the observation of the naturally occurring genetic variation and controlled genome perturbation, to unravel disease relevant pathways. We will perform a genome-wide association (GWA) analysis complemented by long read sequencing to identify genetic modifiers of onset, phenotype and progression of RFC1 disease. We will take advantage of the Crispri technology in genetically engineered iSensoryNeurons to further investigate the effect of GWA loci and to identify additional factors which can modulate RFC1 expression and ameliorate or exacerbate the molecular phenotype. As modifiers are likely to act at cell specific and dynamic level, genetic data will be paralleled by single-cell approaches in post mortem cerebellum and dorsal root ganglia, as well as IPSC sensory neurons and cerebellar organoids. Finally, given a high carrier frequency of RFC1 expansion nearing one out of ten people, we will try to understand whether the repeat itself can act as a modifier of common health and disease traits at population level. The results will hopefully lead to a better understanding of disease causing mechanisms and identify potentially druggable targets. The study output may also have broader implications considering the central role of DNA repair in neuronal functioning and ageing.

Mots-clés : repeat expansion diseases,ataxia,neuropathy,genetic modifiers,gwas,crispri screening,long read sequencing
Projet ERC : SOCIO-CLIMP (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Human Mobility, Environment, and Space
Entité participante : University College de Londres — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497696.0 €

As climate change and extreme weather escalate across Europe, understanding the socio-demographic dimensions of climate events, environmental hazards, and their health consequences becomes increasingly vital. This is particularly important for designing more equitable strategies of environmental protection and climate adaptation, as well as facilitating healthier and more just societies. SOCIO-CLIMP has three primary objectives. 1) Investigating socio-demographic inequalities in exposure to extreme weather events, including their intersection with environmental hazards. 2) Analysing the disparities in vulnerability to extreme weather events - physical and mental health impacts of exposure - according to socio-demographic characteristics. 3) Evaluating how variations in individual and residential contexts contribute to inequalities in exposure and disparities in physical and mental impacts.  SOCIO-CLIMP analyses the socio-demographic correlates of exposure to climate events and environmental hazards using harmonised demographic data across 30 European countries from the 2021 census at a granular spatial resolution. It combines the spatial data with individual-level panel data in the UK and Germany to provide groundbreaking insights into the physical and mental vulnerability (as the cumulative health burden) of different socio-demographic groups to these climate events.  SOCIO-CLIMP represents an innovative effort to understand the socio-demographic inequality in climate change impacts across Europe. It will transform our comprehension of who is exposed to climate change, where specific sub-populations are particularly exposed, how vulnerable these groups are to exposure, and what can be done to effectively mitigate the negative impacts. It will uncover vital insights into social disparities related to climate change, inform targeted interventions, and contribute robust evidence for addressing the demographic and social challenges of climate change.

Mots-clés : climate justice,environmental inequality,residential segregation,exposure to extreme weather,health impacts of extreme weather
Projet ERC : TactileLang (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : University College de Londres — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1954541.0 €

Extensive research over many decades has illuminated the human capacity for language through the study of spoken languages. In the past 20 years research into visual sign languages have provided us with important and unique insights into human language that could not have been obtained by studying spoken languages alone (Emmorey, 2023). For example, we now know that visual sign languages are just as linguistically complex as spoken languages and that developmental and/or acquired language disorders can impact visual sign language perception, production and processing (Mason et al., 2010). We also know that areas in the brain used for spoken language processing are also recruited for visual sign language processing (MacSweeney et al., 2008). Language can also be perceived through touch: the tactile modality. Some deafblind individuals communicate using tactile sign language, as spoken and visual sign languages may be inaccessible for them. There is some linguistic documentation of tactile sign language in countries such as Sweden (Mesch, 2001), the USA (Edwards, 2017) and India (Kusters, 2017). There is still a dearth of research on tactile sign language in the U.K, and worldwide, and compared to spoken and visual sign languages (Simcock et al, 2024). Studying tactile sign language may lead to valuable insights into the nature of human language. This deeper understanding of tactile sign language will enhance our ability to support deafblind individuals and promote their fuller participation in society. To gain those insights, I propose a novel, multidisciplinary and ground-breaking approach where I will document tactile sign language in British deafblind individuals using linguistic ethnography and corpus linguistics methodologies. I will also use a state-of-the-art functional Near-Infrared Spectroscopy (fNIRS), to explore whether the classical areas for processing spoken and visual sign languages are also used for tactile sign language processing.

Mots-clés : deafblind,deafblindness,bsl british sign language,tactile sign language,language documentation,language change,language processing,corpus linguistics,linguistic ethnography,neuroscience
Projet ERC : BrainGate (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1499514.0 €

In contrast to other organs, the brain is surrounded by a system of specialized anatomical barriers isolating it from direct contact with immune cells and microbial products present in the blood. However, such factors do dynamically shape brain function in homeostasis and disease. Because of this unusual anatomy, the pathways of blood-brain communication are still poorly understood, while this understanding would provide a fundamental insight into brain function regulation, and enrich the current knowledge of neurological disease mechanisms. My previous work suggests that the choroid plexus (CP) is a central player mediating the influence of immune and microbial signals on the brain. The CP epithelium is a monolayer barrier tissue, which on the side facing the blood has the ability to sense such peripheral factors, and on the side facing the brain, produces the cerebrospinal fluid (CSF)–a liquid carrying nutrients and signaling molecules, which contacts nearly all brain cells, and ensures brain homeostasis. I therefore hypothesize that peripheral immune and microbial factors may shape brain function indirectly, via regulation of the CSF properties at the CP epithelium. Based on our preliminary data, and building on my past expertise in CP biology, neuroscience and immunogenomics, here I propose an interdisciplinary project BrainGate, striving to illuminate the physiological mechanisms and roles of gut-blood-CP-brain communication axis during post-natal development (Aim 1), under conditions of microbiota perturbation (Aim 2) and along the circadian cycles (Aim 3). By developing new tools for CP-specific genetic perturbation and combining them with approaches of spatial transcriptomics and behavioral readouts in mouse models, this project will reveal fundamental principles of physiological regulation of brain development, function and maintenance and pave the way for future investigation of the gut-blood-CP-brain communication circuit in neurological disease.

Mots-clés : choroid plexus,cerebrospinal fluid,behavior,immunogenomics,immune stromal interactions,
Projet ERC : TDVision (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université Radboud de Nimègue — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 900000.0 €

What we see depends on what we have in mind. For example, we can quickly find tomatoes in the vegetable department of a supermarket by searching for red and round objects, making them stand out from the background. This is thought to be supported by top-down processing within the hierarchy of areas in the visual cortex, but the detailed neural mechanisms are still poorly understood, partly because of limitations in neural recording technologies. In my lab, we recently developed a three-photon microscope capable of visualizing the activity of large populations of individually-defined neurons in awake and behaving macaque monkeys. Combining this novel imaging modality with well-controlled behavioral tasks provides the exciting opportunity to investigate the neural mechanisms of generative vision at an unprecedented scale and level of detail. We will train macaque monkeys to search for shapes hidden in noisy texture elements, investigate the strategy used by the prefrontal cortex to encode the mental template to guide this search, and how this process warps the encoding of visual information in nearly complete local populations of neurons in early visual areas. We will investigate the topographic organization of the recorded population of neurons, and develop viral and histological tools to determine their cell types as well as their connectivity profiles. We will also use psychophysics to make a link to conscious perception in humans, investigating how a search template can warp perception. Finally, we will incorporate our empirical findings into artificial neural network models with interpretable circuit mechanisms. This is expected to bring the flexibility and robustness of generative vision into models of artificial intelligence, as well as provide a computational framework to define novel hypotheses about the detailed neural mechanisms of generative vision in primates, which we can subsequently test with both behavioral measures and in-vivo recordings.

Mots-clés : selective attention,working memory,top down processing,extra classical receptive field,topographic organization,non human primates,3 photon imaging,human psychophysics,recurrent neural network model
Projet ERC : i2 (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Université Radboud de Nimègue — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498894.0 €

A popular view in the history of philosophy and science holds that we only conceive what is in some sense possible and cannot truly understand anything intrinsically contradictory. The Chimera is the paradigmatic example of such an inconceivable absolute impossibility in medieval logic. "Chimera" is a necessarily empty term lacking signification and reference. Analogously premodern mathematics dismisses the square root of a negative number as the impossible result of an impossible operation, i.e. something as nonsensical as the Chimera. Yet by the 16th century complex numbers–i.e. those numbers having an imaginary part i = the numerical value of [root–1]–start being used and problematised. Somewhere down the line these "impossible numbers" had become conceivable and manipulable. How and why did this shift happen? i2 seeks the answer in the late medieval semantics of necessarily empty terms. In the 14th century, Marsilius of Inghen (ca.1341-96) makes terms like "Chimera" properly signifying, understandable and referential in his semantics. Marsilius' account of imaginable absolute impossibilities is widely influential in the 15th and 16th centuries. Girolamo Cardano–credited with the philosophical problematisation of complex numbers–seems at least partly aware of this Marsilian tradition. Marsilius' semantics of imaginable impossibilities, its later reception and its possible influence on Cardano have not yet been explored. This is what i2 is set to do for the first time, through a key-concept analysis and the applications of the method of historical and rational reconstruction to a rich textual corpus. i2 will produce a groundbreaking account of the rise of complex mathematics in relation to the medieval semantics of impossibility and imaginability. Based at Radboud's Center for the History of Philosophy and Science, and advised by an international board of scholars, i2 will deliver high-impact outputs in top journals, two books and knowledge dissemination results.

Mots-clés : history of medieval logic marsilius of inghen imaginabilia history of the philosophy of mathematics
Projet ERC : HANDWAVE (Horizon Europe, appel 2025, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
Entité participante : Université Radboud de Nimègue — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499980.0 €

HANDWAVE will develop a novel framework for understanding the neurobiology of multimodal language, by uncovering the multi-timescale oscillatory mechanisms that enable the flexible integration and weighting of auditory signals, such as speech, and visual signals, such as visual speech and hand gestures. Understanding how the brain integrates and weights these signals is crucial for understanding how natural language is processed in the brain. This knowledge is vital for diagnosing and treating language-related disorders, and for developing effective diagnostic tools and rehabilitation strategies. Two key gaps remain unaddressed. First, historical models on the neurobiology of language have predominantly focused on unimodal speech signals, overlooking the inherently multimodal nature of language. Second, it is unknown how the complex temporal relations between auditory and visual signals allow them to be integrated into one coherent percept. HANDWAVE addresses these gaps by testing the central hypothesis that the brain’s flexible coordination of multi-timescale oscillations enables the integration and weighting of auditory and visual signals through (interactions between) phase modulations, power modulations, and functional connectivity. Work package (WP) 1 will uncover the oscillatory mechanisms underlying the integration of speech and visual signals, and whether and how this gives rise to emergent multimodal representations in the brain. WP2 will examine the oscillatory mechanisms underlying the flexible weighting of auditory and visual signals. WP3 will provide causal evidence for the role of oscillatory mechanisms in supporting integration and weighting. By uncovering the multi-timescale oscillatory mechanisms underlying these processes, HANDWAVE has the potential to redefine theoretical models of the neurobiology of language. Its findings will inspire clinical interventions and communication technologies that better capture the multimodal nature of language.

Mots-clés : gesture visual speech speech noise speech gesture integration multimodal language multimodal integration neural oscillations neurolinguistics
Projet ERC : DEUCE (Horizon Europe, appel 2022, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université Radboud de Nimègue — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 736768.71 €

Reinforcement learning (RL) agents learn to behave optimally via trial and error, without the need to encode complicated behavior explicitly. However, RL generally lacks mechanisms to constantly ensure correct behavior regarding sophisticated task and safety specifications.  Formal verification (FV), and in particular model checking, provides formal guarantees on a system's correctness based on rigorous methods and precise specifications. Despite active development by researchers from all over the world, fundamental challenges obstruct the application of FV to RL so far.  We identify three key challenges that frame the objectives of this proposal. (1) Complex environments with large degrees of freedom induce large state and feature spaces. This curse of dimensionality poses a longstanding problem for verification. (2) Common approaches for the correctness of RL systems employ idealized discrete state spaces. However, realistic problems are often continuous. (3) Knowledge about real-world environments is inherently uncertain.  To ensure safety, correctness guarantees need to be robust against such imprecise knowledge about the environment.  The main objective of the DEUCE project is to develop novel and data-driven verification methods that tightly integrate with RL. To cope with the curse of dimensionality, we devise learning-based abstraction schemes that distill the system parts that are relevant for the correctness. We employ and define models whose expressiveness captures various types of uncertainty. These models are the basis for formal and data-driven abstractions of continuous spaces. We provide model-based FV mechanisms that ensure safe and correct exploration for RL agents. DEUCE will elevate the scalability and expressiveness of verification towards real-world deployment of reinforcement learning.

Mots-clés : formal verification,model checking,safe reinforcement learning,decision making under uncertainty,markov decision process
Projet ERC : SUCCESSion (Horizon Europe, appel 2024, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 1497740.0 €

Mutant cells are abundant in normal tissues, but only very few will transform into life-threatening cancer. The triggers for these mutant clones to transform are unclear. Phylogenetic studies of solid cancers hinted towards an impact of the order of mutation acquisition on the malignant potential of mutant clones. However, to date, no functional studies exist validating these findings in the in vivo context.  Mutant clones closely interact with their environment. Intravital microscopy experiments from my lab showed that phenotypically normal, but mutant clones in the mammary epithelium, the tissue of origin of breast cancer, dynamically rewire their environment in a mutation-specific manner. Hence, I hypothesize that the transforming potential of a mutant clone does not lie in the combination of mutations, but rather in the order in which these mutations were acquired, and thus the way in which the environment of the mutant clone was sequentially rewired, leading to a permissive or a resistant environment for tumour initiation. Tools to study sequential acquisition of mutations in vivo do not exist. Therefore, the possibility that one mutation may need to precede the other for a mutant clone to transform, has not been studied. SUCCESSion will fill this gap and develop a novel sequential somatic gene editing technology. This will be combined with intravital imaging and transcriptional profiling to study for the first time the effects of different sequences of mutations on cell behaviour and sequential rewiring of the micro-environment in the mammary gland. SUCCESSion will have a ground breaking impact from a technical point of view as it will establish a novel way of modelling pre-cancer in vivo, and from a biological point of view as it will elucidate the temporal evolution of pre-cancer in unprecedented detail. This will lead to better understanding of tumour initiation and improve risk prediction enabling early interventions to stop the cancer before it starts.

Mots-clés : mammary gland tumor initiation normal phenotype mammary organoids intravital microscopy lineage tracing somatic engineering