Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : TREATLIVMETS (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : Partner
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 128535.0 €

Liver metastases commonly develop in up to 50% of patients with various cancer types. The most common cancer that metastasizes to the liver is colorectal cancer (CRC). At least 25% of CRC patients develop colorectal liver metastases (CRLM) during their illness. CRLM represent the major unmet clinical need for this malignancy, as the 5-year survival rate of patients with unresectable disease does not exceed 2%. New therapies that promote antitumor immunity have been recently developed, mostly focusing on enhancing T cell responses. Although these therapies have led to unprecedented successes, only a minority of patients benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in next generation immunotherapies. Given the crucial role of innate immune responses in immunity, targeting these responses opens up new possibilities for tumour control. We hypothesize that the immunotherapy of liver metastases can be significantly improved through harnessing the biology of innate lymphoid cells (ILC), such as Natural Killer (NK) cells and ILC1s, and myeloid cells such as macrophages and DCs. Our team brings together experts in the biology of tissue-resident myeloid (Ginhoux, PI4) and lymphoid (Gasteiger, cPI) cells, in liver immunology (Fumagalli, PI3), and in the development of novel immunotherapeutic strategies that modulate immune cells in the fight against cancer (Vivier, PI2). By combining cutting-edge single cell and spatial transcriptomics of human patient samples with cross-species analyses in advanced genetic mouse models, we aim (1) to identify cellular interactions defining the metastatic tumor microenvironment across murine and human tissue-specimens, (2) to investigate immune cell functions regulating metastatic disease using a unique combination of advanced genetic mouse and human tissue models, and (3) to harness the anti-tumoral functions of innate immune cells via next generation cell engagers.

Mots-clés : liver immunology,liver metastasis
Projet ERC : DECOLeishRN (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Université Bar-Ilan — Pays : Israël — Rôle : PI
Acronyme de l'entité : BIU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2985000.0 €

Darwinian evolution plays a central yet poorly understood role in human disease. Iterations between genetic mutation and environmental selection drive cancer development, microbial infection and therapeutic failure, thus increasing human mortality. The molecular mechanisms that harness the deleterious effects of genome instability to generate beneficial phenotypes in these pathogenic systems are unknown. Here we investigate this important unsolved question in the protozoan parasite Leishmania that causes devastating human infections. In the absence of transcriptional regulation, these early-branching eukaryotes exploit genome instability to regulate expression by gene dosage. Leishmania thus represents an ideal system to investigate how genome instability drives fitness gain in fast evolving, eukaryotic cells, such as observed during cancer development. Synergizing our expertise in genomics, evolution, systems and RNA biology, we have recently made several breakthrough discoveries that link parasite fitness gain to epistatic interactions between co-amplifying genes of small, non-coding RNAs, which program epitranscriptomic and translational regulation. We hypothesize that these genome/RNome interactions generate the phenotypic landscape underlying Leishmania fitness gain. Our proposal investigates this ground-breaking concept through two Specific Aims that (i) combine experimental parasite differentiation and evolution in vitro and in vivo to reveal molecular mechanisms underlying Leishmania predictive adaptation and fitness gain, and (ii) investigate how RNA modification and non-coding RNAs contribute to adaptation by regulating mRNA stability and translational control. Our findings will be highly relevant to other fast growing, eukaryotic systems that rely on genome instability, such as cancer or fungal pathogens.

Mots-clés : eukaryotic fitness gain,genome instability,leishmania,non coding rna,post transcriptional control,translational regulation
Projet ERC : FireSpace (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Université de Gand — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3116250.0 €

The "FireSpace" research proposal aims to address the critical challenge of fire safety in space exploration, particularly in environments with increased oxygen concentrations, reduced pressure, and reduced gravity. The main objective is to generate fundamental knowledge on the fire behavior of materials used in spacecraft and habitats under these extreme conditions and to develop strategies for mitigating fire risks. This will be achieved through a combination of experimental investigations, the development of fire-retardant (FR) materials, and advanced numerical simulations. The key objectives of the project are to: 1. Passive fire mitigation: Understand the fire behavior of FR materials in reduced gravity and oxygen-rich environments. Develop new FR materials and advanced diagnostics for testing these materials in microgravity. 2. Active fire mitigation: Formulate strategies for controlling flame spread through environmental perturbations such as acoustic or electromagnetic waves. 3. Numerical simulations: Perform detailed simulations of fire spread from material to compartment scales, predicting the effectiveness of fire safety strategies in spacecraft and space habitats. 4. Risk management: Consider the interplay between fire safety and other critical habitation systems, ensuring a balanced approach to risk management in space missions. The research will be structured into seven work packages (WPs) involving the design of FR materials, development of experimental rigs for microgravity platforms, and integration of fire safety into spacecraft design. This holistic approach will generate groundbreaking knowledge to enhance the fire safety of future space missions.

Mots-clés : fire retardancy,flame retardant,flammability,fire safety,combustion,fire spread,cfd modeling,numerical simulation,reduced gravity,space exploration,spacecraft,diagnostics
Projet ERC : SUNRISE (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : CO-PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 2817717.0 €

Paediatric tumours represent a challenge in the landscape of cancer research. Unlike adult cancers, they typically originate from embryonic cells, from which they inherit characteristic embryonic features. This is exemplified by neuroblastoma (NB), the most common solid tumour in young children. NB is a heterogeneous cancer with aggressive metastatic forms, which emerges from neural crest cells. These cells normally undergo a complex migratory process that depends on the functions of cell surface signalling receptors. In a recent, ground-breaking study we found that NB cells co-opt one specific family of these receptors (UNC5) and the ligand GPC3 to disseminate (Cell 2022). Disruption of this interaction in vivo impacted on cell cohesion, migratory properties and redirected tumour localisation. Here we provide unpublished data analysis, suggesting that an entire UNC5 interaction network, involving multiple different ligands besides GPC3, is at play in malignant NB. Understanding the mechanisms driving NB cell aggressive behaviours requires investigation of this network in the embryonic context. A key strength of the proposal is our unique approach bringing molecular/structural biology to in vivo experiments. Our strategy maximises the use of targeted, structure-based perturbation experiments, where we control the activity of individual receptor interaction precisely, in vivo. We also have the necessary access to patient samples and will use our innovative avian xenograft model which recapitulates the embryonic environment of NB. In a final workpackage we will apply our strategy, developed with a focus on NB, to two other paediatric cancers where UNC5 is expressed. In sum, the results of SUNRISE will produce a first detailed picture of the ‘where’, ‘when’ and ‘how’ UNC5 network interactions drive paediatric cancer biology, and could lead to new therapeutics, for example, using nanobody technology.

Mots-clés : membrane receptor,cell migration,cell cell interactions,neuro developmental cancer,neuroblastoma,structural biology,embryonic neuro development
Projet ERC : NASCE (Horizon Europe, appel 2024, Synergy grants)
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 : 3544851.0 €

In an office, on a metro, or at home, diverse sounds may be surrounding you: a computer fan, footsteps and indistinct chatter, distant cars, the train slowing down. These sounds shape our environmental awareness, even when visual cues are absent. Despite its ecological relevance, understanding how our brain parses the acoustic scene into semantic objects remains a major scientific challenge. Moreover, individuals with hearing impairments, including those relying on hearing aids or cochlear implants, face challenges, both auditory and cognitive, in environments with multiple sound sources. The NASCE project aims to mechanistically comprehend real-world auditory scene analysis (ASA) through a novel framework: the Semantic Segmentation Hypothesis (SSH). The SSH posits that semantic representations drive real-world ASA, shifting the focus from early acoustic processing to the semantic analysis of everyday sounds. It addresses fundamental questions, such as: How does the brain create semantic sound source representations? How do they interact with acoustic processing, and aid our ability to recognize sounds in a scene? NASCE integrates cognitive psychology, neuroscience, and AI methods. Employing neuroimaging and behavioral paradigms, we aim to reveal how the brain dynamically represents auditory scenes across brain regions for relevant listening tasks. Using deep neural networks and ontologies, we aim to construct neuroscientifically grounded computational models simulating cerebral and behavioral responses under the same scenes and tasks as in the experiments. Finally, with advanced analytical methods we will consolidate behavioral, computational, and neuroscientific insights and establish SSH as a groundbreaking theory of ASA. NASCE promotes a paradigm shift, fundamentally reshaping our comprehension of ecological hearing. Moreover, it paves the way for the applications in machine hearing of computational models that mimic human auditory cognition.

Mots-clés : natural sounds sound scene soundscape auditory scene analysis acoustics semantics deep neural networks functional magnetic resonance imaging fmri magnetoencephalography meg intracranial electroencephalography ieeg representational similarity analysis rsa connectivity
Projet ERC : GWSky (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 3265398.25 €

General Relativity (GR) is more than a century old, but is still our best macroscopic description of gravity. Key GR predictions are black holes (BHs) and gravitational waves (GWs), whose spectacular confirmation led to two recent physics Nobel Prizes. The future of GW astronomy, however, is even brighter, since detectors will observe BHs at cosmic dawn and probe their enigmatic event horizon, where GR clashes with quantum mechanics in the information loss paradox. These experiments will measure signals hundreds of times smaller than today, necessarily discovering anomalies and deviations from current predictions, e.g., due to the astrophysical environment. On the fundamental side, precision GW astronomy will open countless possibilities for understanding the standard model of particle physics (and its extensions), gravity and cosmology. By itself, however, precision is not knowledge. To harness the power of these measurements, a groundbreaking framework is urgently needed to solve the very nonlinear equations of GR and develop waveform models to unprecedented accuracy, and to convert these results into concrete interpretation tools. GWSky will leverage the world-leading expertise of its PIs in astrophysics, GW-source modeling, particle physics and GR, and recent paradigm shifts to build an overarching framework answering a fundamental question: When, inevitably, an anomaly in a GW signal is identified, what is it? A gravitational effect not predicted by GR? The influence of nearby matter? Or merely an imprecise calculation of the expected signal? Even tiny deviations from GR would shake physics to its core, but to claim a deviation from it, one needs to filter out first the contributions from the astrophysical environment, instrumental artifacts and systematic modeling uncertainties. GWSky will provide tools to disentangle these contributions, enabling precision GW astronomy with upcoming observational runs, and new facilities on the ground and in space.

Mots-clés : the two body problem in general relativity
Projet ERC : CARAMEL (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Université Constructor — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2489421.0 €

Finding new synthetic compounds that facilitate membrane transport of impermeable bioactive molecules constitutes one of the grand scientific challenges in chemistry, biology, and medicine. Until today, the design principles of artificial transporters have been mainly restricted to membrane-targeting molecules with segregated hydrophilic and hydrophobic domains. We propose a disruptive strategy that uses boron clusters as membrane carriers that abandon the classical amphiphilic topology and exploit the (super)chaotropicity of boron cluster anions. Chaotropicity, historically associated with the salting-in effects of ions on proteins, has only recently been related to the affinity of large cluster ions to hydrophobic surfaces. In comparison to amphiphilic carriers, boron clusters are fully inorganic, highly water-soluble, globular in shape, and induce direct membrane transport despite being anionic in nature. The mere existence of these carriers defies all previous conceptual assumptions and biomimetic design criteria. Here, we introduce a new scenario for chaotropic membrane transport. A new chaotropic strategy will be introduced. A systematic transport screening will be carried out to study the fundamental physicochemical parameters and to generate a cargo-dependent predictive model for covalent chaotropic transport. Functional biomolecular hybrids will be validated to achieve proof-of-principle for the therapeutic potential. This proposal is aimed to fully unfold the potential of the new chaotropic scenario and intended to shake the very foundations of research in membrane transport.

Mots-clés : lipid bilayer,membrane transport,synthetic membrane carriers,peptide chemistry,counterion activation,boron clusters,intermolecular interactions,boron clusters,chaotropic materials,extracellular vesicles,protein delivery
Projet ERC : DynAMiCs (Horizon Europe, appel 2024, Synergy grants)
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 : 2818271.25 €

Discrete dynamical systems pervade the quantitative sciences, and lie at the heart of central computational challenges in a wide variety of areas, from program analysis and computer-aided verification to neural networks and theoretical biology. Such systems are typically simple to describe, yet give rise to a rich algorithmic and mathematical theory that is replete with easily stated and compelling open problems. One such example is the famous Skolem Problem: does the orbit of a given linear dynamical system ever hit a given hyperplane? The decidability of this question is a longstanding open problem going back nearly a century!  The main goal DynAMiCs is to achieve major advances in the algorithmic theory of discrete linear dynamical systems and related formalisms. Whilst our motivation and outlook originate from computer science and automated verification, we approach these challenging problems from both mathematical and computational angles, combining tools and techniques from number theory (e.g., Diophantine approximation, transcendence theory, continued fractions), symbolic dynamics (e.g., word combinatorics, subshifts, numeration systems), and mathematical logic (e.g., monadic second-order logic, Presburger arithmetic, automata theory). One of our leading objectives is to substantially broaden the classes of dynamical systems and properties that can be algorithmically handled via model checking. We aim to achieve these ambitious advances by pursuing new approaches to central open problems in linear systems, such as the Skolem Problem, building on recent breakthroughs in these areas (some of which from the PIs and their groups).  We take on this challenge with a team of PIs consisting of international leaders in algorithmic verification, symbolic dynamics, and analytic number theory. We believe our complementary expertise places us in a unique position to achieve major breakthroughs in longstanding fundamental problems in the area of discrete dynamical systems.

Mots-clés : model checking decidability linear dynamical systems recurrence sequences diophantine approximation symbolic dynamics continued fractions monadic second order logic presburger arithmetic
Projet ERC : UnMySt (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 2430000.0 €

Polaritonic Chemistry is a new and exciting field that has emerged from the fusion of chemistry and cavity quantum electrodynamics. In this innovative realm, and specifically under Vibrational Strong Coupling (VSC), hybridizing molecular vibrations with electromagnetic cavity modes has been shown to modify the rate and yield of reactions, solvent polarity and other molecular properties, in the absence of any illumination. The prospects for VSC as a versatile tool for chemistry and materials science have sparked a worldwide surge of interest, leading to substantial advances in recent years. Nevertheless, deciphering the underlying mechanisms by which VSC affects material properties still poses formidable challenges, impeding the utilization of VSC to its full potential. The goal of UnMySt is to construct a complete framework for cavity-controlled chemistry, built upon a comprehensive mechanistic understanding of VSC on both the molecular and supramolecular levels. As leading scientists in the field, we will pursue this goal by joining our forces in seeking answers to these pivotal questions: 1. What is the mechanism that links the local character of molecular reactivity with the collective nature of VSC? 2. Do the thermal equilibrium properties of materials change under VSC and how are such modifications expressed in polaritonic chemistry? 3. What are the manifestations of VSC on non-equilibrium dynamics such as solvent reorganization or charge transfer? 4. Can symmetry considerations provide intuitive guidelines for cavity-controlled chemistry? Can symmetries imposed or broken by the cavity be used to tailor its impact on reactivity? Our synergistic experimental and theoretical efforts will reveal novel physical mechanisms and will lay the qualitative and quantitative foundations for the rational design of strongly coupled molecular systems. The results of UnMyST will unleash the potential of polaritonic chemistry as a new tool for synthesis and materials science.

Mots-clés : cavity polaritons,polaritonic chemistry,vibrational strong coupling,spectroscopy,electronic structure,molecular dynamics,electronic structure methods,quantum electrodynamics density functional theory
Projet ERC : MAGNESIS (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Société Max-Planck pour le développement des sciences — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Société Max Planck
Type d'entité : Recherche
Financement ERC de l'entité : 2486875.0 €

In the last years, electrochemistry and electrocatalysis are increasing their impact across several fields. A major driving force comes from the promise of substituting current fossil-fuel powered thermal methods in the industry by electrochemical alternatives, driven by renewable electricity. However, electrochemical methods are still far from reaching the desired target performance. In this landscape, the recent discovery of magnetic fields enhancing electrocatalytic processes offers a plausible new strategy. The idea of boosting an electrocatalytic reaction by an external magnetic field becomes highly persuasive. Still, the origin of this phenomenon is hardly understood, given its complexity: dealing with a magnetic field, in an electric field, on a dynamic surface, during a chemical reaction is a multiple-body problem.  Our objective is to foster magneto-electrocatalysis by exploring rigorously the interplay between magnetic fields and electrocatalytic performance from atomic resolution in model systems up to full cell devices. This can only be achieved by a synergetic effort between experts in catalysis, surface science, magnetism and theory. We will focus on two relevant reactions: the spin-restricted water oxidation and the carbon dioxide reduction, both potentially spin-sensitive. Our aim is to validate the structural, electronic and magnetic key descriptors controlling this phenomenon, assessed by complementary ex-situ and operando data within the corresponding theoretical framework. Computational tools will consolidate the understanding and quantify the different mechanistic contributions to microscopic and macroscopic observations. The ambition with MAGNESIS is to define, in a rigorous way, the first principles and ultimate possibilities of magnetic fields in the development of advanced electrocatalytic methods, pioneering the novel field of magneto-electrochemical science & technology.

Mots-clés : magnetoelectrocatalysis,electrocatalysis,dft calculations,microscopy,multiscale modelling,magnetism,water electrolysis,water splitting,co2 utilisation