Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Beta-STEALTH (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Leiden University Medical Center — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : LUMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Type 1 diabetes (T1D) is generally believed to result from a mistake by the immune system leading to the autoimmune destruction of insulin-producing β-cells in the pancreatic islets of Langerhans. Based on my discoveries, I recently began to realise that the ‘mistake’ actually occurs in stressed β-cells, leading to the generation of neoantigens resulting from ribosomal infidelity (DRiP) that provoke the immune system to act. The immune system may actually respond with ‘good’ intentions, similar to the response to such neoantigens generated upon infection and in cancer. This could explain why immune intervention therapy alone has been quite disappointing in T1D, where the loss in β-cell function could at best only be delayed. I contend that we will need β-cell therapy for a durable intervention or even remission, likely in concert with immunotherapy, to keep β-cells from provoking the immune system. Thus, I propose to explore β-cell stress, autoimmunity, resilience and function in three levels: Pathogenesis: understand the association of protective insulin gene variation with reduced β-cell stress and immunogenicity; explore the nature and function of β-cell stress product DRiP in β-cell development, heterogeneity, function and destruction; Diagnostics: target DRiP to detect β-cell stress, immunogenicity and destruction; monitor autoimmunity to DRiP by islet autoreactive T-cells or autoantibodies; Therapeutics: develop targeted delivery of drugs to distressed β-cells to foster recovery, mass and function and increase their stamina; restore immune tolerance by selective immunotherapy with islet neoantigens; generate a novel source of stem cell derived β-cells that have been equipped with resilience and superior function by gene-editing to reduce both stress and generation of neoantigens. Through these objectives, I intend to eliminate the reasons for the immune system to harass β-cells by harnessing β-cells and turn these invisible (‘stealth’) to the immune system

Mots-clés : type 1 diabetes immuno pathogenesis autoimmune disease islet transplantation immunotherapy genetics regenerative medicine stem cell therapy
Projet ERC : HUMANFACE (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Compl exity
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 : 2499851.0 €

HUMANFACE is based on a proposed global theory of human face identity recognition, conceptualized as a categorization function (i.e., Face Identity Categorization, FIC). FIC is considered as the pinnacle of categorization in human adults, who perform this function rapidly and automatically, despite a large, undetermined, and flexible number of categories of identities experienced throughout life. The core theoretical hypothesis of HUMANFACE is that semantic representations of person identity precede and guide the development of visual face identity representations throughout lifetime. Hence, contrary to standard theoretical models, there is no border between “visual perception” and “semantic memory”, but a postero-anterior gradient of sensitivity to physical and semantic features of identity in the human ventral occipito-temporal cortex (vOTC). The theory integrates a number of observations from single neurons to behavior, making predictions tested in five work packages. In WP1, valid measures of rapid, automatic FIC in human adults are optimized, to be used in WP2, testing the modulation of FIC by, and integration with, social semantics. To map the neural basis of FIC as constrained by social semantics, including its temporal dynamics and critical relation to behavior, WP3 consists of intracerebral recordings and stimulation across the vOTC. To show the emergence and strengthening of representations of facial identity by multimodal person knowledge, studies in infants and children will be conducted in WP4. Finally, to test hypotheses about the coding of facial identities across degenerate minicolumns of neurons, recordings will be made at the level of single neurons in the vOTC in WP5. The project will generate a large corpus of data and original methodologies to make decisive progress in understanding one of the most complex functions of the human mind/brain, shedding new light on how humans give meaning to their physical and social environment.

Mots-clés : face recognition,human brain,categorisation,semantics,social perception
Projet ERC : SeaLi2Bio (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
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 : 1338199.0 €

Lithium (Li) is key in the energy transition and massively used to produce mobile devices and electrical vehicles. Yet its current consumption rate exceeds its river flux to the ocean, and it is poorly recycled, while Li excess is toxic for aquatic life and humans. Although concentrations of Li and its isotopes have been measured in coastal waters, at river outlets, to study continental chemical weathering and climate controls, Li monitoring has been occasional. Moreover, bias caused by anthropogenic inputs is not quantified. Combining a novel isotopic methodology with ecotoxicology and biology approaches, SeaLi2Bio will first determine and understand the littoral Li contamination sources, flux and controls, and quantify its current contribution to the Li cycle. Plankton, macroalgae and bivalves will act as long-term bioindicators at reference sites located along urbanisation gradients. The biological controls of Li isotopes will be determined by aquaculture of model organisms, over a range of representative environmental and metabolic conditions, and confronted to in situ measurements. Upscaling from regional to global scale will be achieved with a multivariate statistical model accounting for geospatial data on watershed characteristics, population density and socioeconomic parameters. This project will also anticipate future environmental and health issues caused by Li contamination, focusing on the North Chile coast where Li levels are known as the highest, and using innovative health-monitoring tools (Cu-Zn isotopes). Finally, the evolution of Li contamination will be simulated at the continental and global scale, following scenarios of energy transition impacting differently Li demand and waste. By disentangling the factors of Li contamination from the natural background, SeaLi2Bio will assemble a first robust reference for a global issue tied to the history of climate and its future evolution in response to reduction of fossil fuels use.

Mots-clés : non conventional isotopes,trace metals,environment
Projet ERC : CONFINED (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Soci al World and Its Interactions
Entité participante : Université Griffith — Pays : Australie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 161077.5 €

CONFINED will develop and validate an innovative, comparative, and global research agenda of confined lives. Confinement is a ubiquitous and unequally distributed human condition. While confinement sometimes can be protective, for some groups, not least the displaced on dangerous roads, the marginalized in urban slums and the detained in prisons, it can be a damaging experience linked to violence and inequality. With an empirical point of departure in different contexts across the global north and south, known to produce a variety of confined lives, CONFINED explores, 1) how certain people’s lives are rendered confineable; 2) how confineable groups and networks navigate discursive, actual, and potential practices of confinement, and 3) how and to what extent the concept of confined lives can transform our understanding of the practices and experiences of confinement across global divides in ways that drive theoretical innovation and help build new agendas for social justice. Through three interdependent and sequentially organized work packages, CONFINED proposes to explore confined lives contextually and ethnographically across the global North and South (WP1); to compare what confines people, how they make sense of their confined lives, and how they navigate confinement (WP2), and to conceptually develop and validate the approach through engagement with academics and experts locally and globally (WP3). CONFINED will carry out comparative, ethnographic field work to follow precariously situated translocal family network across four contexts as a privileged lens to understanding confined lives at the intersection of dangerous journeys, urban slums and prisons and camps: Denmark and Lebanon; South Africa and Malawi; Thailand and Myanmar and the UK and Sierra Leone. This will allow CONFINED to reframe the empirical field of confined lives and to generate a new conceptual language to understand one of the most important drivers of inequality world-wide.

Mots-clés : displacement,urban marginality,incarceration,family and kinship,state and non state violence
Projet ERC : RAVE (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental Constituents of Matter
Entité participante : Organisation des Nations unies pour l'éducation, la science et la culture — Pays : France — Rôle : PI
Acronyme de l'entité : Unesco
Type d'entité : Recherche
Financement ERC de l'entité : 1075000.0 €

With the flourishing of quantum information processing, the study of open quantum system dynamics has become of paramount importance for the ultimate success of quantum technologies. The phenomenology becomes increasingly rich when decoherence and dissipation arise in quantum systems with many degrees of freedom, leading to a flurry of different phases of matter. RAVE is devoted to the study of collective phenomena in synthetic, many-body open quantum systems through investigation of the dynamics of quantum trajectories. Following the dynamics at the level of its trajectories will capture features that are washed out by looking at averaged observables, i.e. in the density matrix. RAVE will show that there are collective phenomena visible only in the dynamics of single trajectories, and propose experimental schemes to observe them. This will lead to a new classification of phases in quantum many-body open systems and help clarify the relations between entanglement, correlations and non-equilibrium thermodynamics. In those cases where the steady-state phase breaks time-translational invariance, RAVE will contribute to unify apparently different concepts such as synchronisation and time-crystals. The statistics associated with the behaviour of quantum jumps in many-body systems is also important for characterizing the quality and performance of quantum information processing protocols. To address the key questions posed by the project, RAVE will develop a promising new methodology based on replicas and use it to design open system quantum simulators able to provide information at the level of single trajectories. RAVE is a highly interdisciplinary programme which will have significant impact in the fields of condensed matter, statistical physics, quantum information and stochastic thermodynamics.

Mots-clés : many body open systems,phase transitions
Projet ERC : mt-REMs (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
Entité participante : Université d'Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Mitochondria-derived reactive metabolites (mt-REMs) drive context-specific immunomodulatory behaviors during metabolic reprogramming. Yet, no method can interrogate the cause-and-effects of individual mt-REMs with locale specificity and temporal resolution. Mapping mt-REM-directed signaling changes with spatiotemporal resolution would thus be transformational. I will develop a spatiotemporally-resolved in-vivo mt-REM-responsivity-mapping technology. This cross-disciplinary innovation will enable localized build-up of an individual mt-REM in one specific cell type with precise temporal, dosage, and chemotype control. For the first time, I will map cell-type-specific “first responders”, proteins attuned to react with the specific mt-REM in an otherwise unperturbed system, in a manner that alters signaling across distinct disease contexts. My ability to assimilate chemical biology, organic/medicinal chemistry, & biotechnology enables me to achieve these goals leveraging functional mechanistic models principally zebrafish, mice, and cultured primary cells. The resulting new knowledge is biomedically important: my previous work on lipid-derived metabolites supports that we can leverage this information to design drug candidates. This research project promises transformative biomedical advances and technological breakthroughs with enormous potential for unveiling reactive metabolite-guided biological mechanisms influencing cell function & disease outcomes.

Mots-clés : chemical biology,biotechnology,bioengineering,reactive metabolite signaling subsystem
Projet ERC : SCULPTABELLUM (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Université d'Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499541.0 €

Long-term memories are consolidated over time, progressively becoming more stable and resistant to interference. The consolidation of motor memories is particularly robust – so much so that we use the term “like riding a bike” to describe things that we never forget. And yet, compared to declarative memory systems, relatively little is known about the neural mechanisms through which motor memories are consolidated in the brain. Several forms of motor learning require the cerebellum, a brain area that is often thought of as a machine-like input-output device in which sensory inputs are combined with state estimation to compute motor commands. However, recent work has emphasized the extent to which cerebellar circuit function is influenced by external features, such as the animal's behavioral state, or the statistics of the environment. Moreover, activity that occurs offline – between experimental sessions and even between individual trials, within sessions – can be crucial for cerebellar function. Here, we will investigate how cerebellar activity is sculpted over time, not only during the execution of cerebellum-dependent behaviors themselves, but also during offline ‘rest’ periods, and across stages of learning, to consolidate recent memories and update the system to allow it to learn new things. We will use temporally precise, cell-type-specific neural circuit manipulations and recordings to ask: 1. What are the mechanisms through which offline cerebellar activity contributes to memory consolidation? 2. What roles does memory consolidation play in long-term motor adaptation and metalearning, or ‘learning how to learn?’ 3. How do climbing fiber inputs to the cerebellum contribute to determining what is learned? Together, these experiments will reveal how cerebellar activity patterns are orchestrated across timescales to enable flexible and coordinated behavior in dynamic environments.

Mots-clés : motor learning,locomotion,associative learning,cerebellum,optogenetics,neural circuits,mouse
Projet ERC : SAFE-H2 (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and Processes 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 : 1968066.0 €

Hydrogen is a powerful energy vector but its deployment at the scale considered today by governments and companies cannot be achieved if safety associated to combustion hazards is not mastered and regulated. Hydrogen leaks occur and lead to fires and explosions which must be prevented. To do this, regulations are needed but these regulations are based today on an incomplete understanding of the fundamental mechanisms controlling the combustion of hydrogen in air or have to consider new usages of hydrogen such as transportation (aircraft, trains, cars…). SAFE-H2 combines theory, high-precision experiments and simulations to provide reliable knowledge on the ignition, propagation, acceleration, mitigation of hydrogen-air flames in three canonical cases: flames stabilized on a hole, flames interacting with a wall, explosions in closed vessels. The proposal gathers (1) IMFT where two experimental sites, dedicated to hydrogen, will be used for low (<40 kW) and high power (300 kW) experiments and (2) CERFACS which provides the High-Performance 3D simulation tools used to compute all IMFT experiments. Experimental diagnostics coming from the aerospace field will be applied to safety scenarios at IMFT to validate simulation tools. SAFE-H2 will focus on generic, simple cases to tackle the fundamentals of hydrogen-air flames so that simulation tools incorporate correct, validated physical models and can replace costly and dangerous experimental tests. All SAFE-H2 experiments will be designed to be used for simulation validations. These detailed comparisons between simulation - experiment will be used to test models for 1) hydrogen-air chemistry in the gas phase and near walls, 2) autoignition and plate ignition, 3) flame-turbulence and flame-wall interaction, and 4) transition to detonation. SAFE-H2 will deliver fundamental science but also models for all simulation codes used in industry and regulation agencies to understand and regulate combustion safety for hydrogen.

Mots-clés : hydrogen safety high fidelity experiments simulation
Projet ERC : SEE-MAGIC (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Laboratoire européen de biologie moléculaire — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 3428458.0 €

Tumorigenesis is an evolutionary process driven by gradual mutation acquisition to confer selective advantages to somatic cells. DNA rearrangements are the most common cancer driver mutation, outnumbering base substitutions. Rearrangements amplify, disrupt and fuse genes or alter their gene regulation, ultimately driving adaptive changes to initiate cancer, metastasis and therapy resistance. Cancer genomics has revealed that most of these alterations arise as complex genomic rearrangements (CGRs), where a multitude of changes arise in a short time. While in most cases deleterious to the cell, in rare cases CGRs confer an adaptive malignant phenotype in one giant-leap through saltatory evolution events (SEEs) – reminiscent of the “hopeful monsters” theorised by Goldschmidt. Given their potential to overcome strong selective barriers, it has been proposed that SEEs draw the line between benign lesions and lethal cancer, and understanding their mechanisms is thus fundamental to tumour biology. However, the identity of cells undergoing SEEs has remained elusive, with cancer genomics studies focusing typically on long-established cancers rather than early or even initiating cancer cells. Intriguingly, CGRs are largely explained by cascades of atypical cell nuclei (i.e., nuclear atypias) fueling rearrangement formation, providing an opportunity to study SEEs. Building a novel automated AI-driven framework that couples imaging and single-cell multi-omics, we will leverage nuclear atypias as a phenotypic indicator to dissect principles and mechanisms of SEEs ‘in the making’, and advance fundamental cancer biology. Using highly controllable cell lines and organoid models of colorectal cancer (CrC), a tumour thought to be driven by SEEs, we will unravel pathways, genetic contexts and chromosome-level constraints determining SEEs. Finally, via validation in patient samples we will pave the way to determining SEEs in future clinical studies to advance precision oncology.
Projet ERC : BEYOND STRESS (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
Entité participante : Essen University Hospital — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2156131.74 €

mTOR kinase is an oncogenic master regulator of metabolism and cell growth and is known to reside in two multiprotein complexes. Upon stress, mTOR is inhibited by stress granules (SGs), which recruit mRNAs and signaling factors to promote survival. Current work largely addresses the functions of SG proteins under stress, focusing on their RNA binding properties and SG assembly. However, non-stress functions are emerging. I propose that SG proteins have prime functions in mTOR signaling at metabolic steady-state, in the absence of SGs. Our preliminary data show that core SG proteins bind mTOR at steady-state and suggest that they are key controllers of mTOR. In BEYOND STRESS, we will investigate SG proteins as a novel class of mTOR regulators at steady-state.  By means of deep proteomics, proteo-metabo-flux, RNASeq, systems modelling, mechanistic and cell bio-logical studies, we will identify and functionally characterize the SG interactome of the mTOR complexes. We will delineate the steady-state inputs that signal through SG proteins to mTOR, and we will unravel the mechanistic interplay through which SG assembly impinges on metabolic signaling upon stress. As levels of core SG proteins correlate with cancer outcome, we will explore their linkage with metabolic signaling, prognosis and drug response in breast cancer. BEYOND STRESS is ground-breaking as (i) it links SG protein research in stress to steady-state mTOR signaling; (ii) a unifying paradigm of mTOR regulation at steady-state and stress will open new horizons for research on metabolic signaling; and (iii) SG proteins are emerging as markers and targets for oncogenic signaling through mTOR. While focusing on mTOR and breast cancer, BEYOND STRESS will likely translate to further networks and tumor entities, opening new avenues to signaling and cancer research.

Mots-clés : metabolic signaling,mtor,lysosomes,granules,nutrients,stress,translation