Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : 4D-BioSTEM (Horizon Europe, appel 2023, Synergy grants)
Entité participante : Forschungszentrum Jülich — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : FZJ
Type d'entité : Recherche
Financement ERC de l'entité : 2498949.0 €

Electron Microscopy (EM) has transformed research in the Life and Physical Sciences separately. Cryo-EM in Life Sciences allows the 3D structure determination of proteins down to 1.0 Å resolution in case they are large enough and present in high numbers in homogeneous states. For many molecules involved in diseases like neurodegeneration, however, structure determination is still severely hampered due to their insufficient contrast when imaged in vitreous ice or in their native cellular environment. To date, EM in the Physical Sciences generated utmost contrast for light atoms and established a resolution in the range of 0.2 Å limited only by thermal motion. This record was achieved by evolving scanning transmission EM (STEM) from a 2D to a 4D imaging technique combining imaging with diffraction. In this project, we will work out 4D-BioSTEM methodologies and develop a cryo-EM tool that maximizes contrast and resolution by bringing together EM groups from Life and Physical Sciences. 4D-STEM imaging of frozen biological specimens will be approached with unique and specialized hardware, theory and simulation, the development of microscope operation routines, and image reconstruction algorithms. In particular, we will acquire sparse 4D data using ultrafast detectors, employ methods for direct phasing (differential phase contrast, DPC) and establish advanced, so-called ptychographic, techniques to gain maximal signal from noisy 4D cryo-STEM data that are limited in their electron dose budget. We will make use of synergies between recently separated fields in order to make proteins smaller than 50 kDa amenable to structure elucidation. Furthermore, we will expand 4D-STEM to tomography, to obtain high-contrast 3D reconstructions from cellular samples, human brain tissue of neurodegenerative diseases, and vitrified organic energy materials. A new comprehensive structural imaging framework will be put forward and benchmarked as to its utility in Life and Physical Science applications of cryo-EM.

Mots-clés : electron microscopy,cryo em,stem,scanning transmission electron microscopy,phase contrast imaging,image processing,automation,imaging neurodegeneration
Projet ERC : METRIQS (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Conseil supérieur de la recherche scientifique — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 3930570.7 €

The quest to design materials with tailored properties is a driving force for new scientific and technological horizons and is critical for addressing the grand challenges of humanity. Our proposal introduces an innovative concept in condensed matter and materials science: heterostructures built upon the fusion of 2D van der Waals materials and freestanding transition metal oxides (TMOs), forming a new compound metamaterial where the interface itself plays a crucial and active role in the properties and functionality. Our strategy is threefold. First, by incorporating a 2D layer between two TMO crystals to prevent ionic-covalent bonding and disorder, we can stack the TMOs with a continuous, free choice of twist angle. This will dial in interfacial superstructures called moiré lattices, which impose profound changes in their physical properties. Second, the moiré lattices will ‘imprint’ ferroic orders in the interfacial 2DL, which then act as a spacer, lubricating layer, and sensing layer in one. Moiré engineering has so far been reserved for van der Waals materials, and with METRIQS, we seamlessly merge TMOs with van der Waals materials, creating a highly versatile hybrid platform, where the interaction strength, strain, and dislocation networks can be controlled. Moiré metamaterials are used to study valleytronics and correlated states, control skyrmions, realise spin-charge conversion devices, and control the nucleation of chiral molecules. Our most ambitious endeavour unfolds in the third phase, where we are committed to revolutionising material synthesis by design. This will be achieved through interface manipulation, employing a combination of static and dynamic techniques, including strain, light, and electric/magnetic fields, in conjunction with the precise control of the bilayer twisted oxide as a tuning knob. This project unites two separate scientific communities and material families, in a team with highly complementary skills, knowledge, and resources.

Mots-clés : metal oxides,perovskites,graphene,transition metal dichalcogenides,van der waals heterostructures,two dimensional materials,spintronics,valleytronics,correlated states,chiral molecules
Projet ERC : KARST (Horizon Europe, appel 2022, Synergy grants)
Entité participante : IFP Energies nouvelles — Pays : France — Rôle : PI
Acronyme de l'entité : IFPEN
Type d'entité : Recherche
Financement ERC de l'entité : 2373533.0 €

Karst aquifers are a treasure and a threat: while up to 25% of the world population depends on them for drinking water, they also have capabilities for extremely fast conduction of water and contaminants. In the light of climate change, we need to prepare for extreme flooding and understand the consequences for karst aquifers. Despite their socio-economic importance, decades of research, and high-profile disasters, karst structures and processes remain notoriously difficult to assess. Because of the complexity of karst and its lack of accessibility, the foundations of flow and transport modeling in karst systems are weak. Key phenomena related to extreme events such as flash floods and heavy tails in tracer recovery are still beyond current modeling capabilities. KARST will establish the next generation of coupled stochastic modeling frameworks to predict karst processes, assess the vulnerability of karst aquifers, and forecast their response to extreme events. Our approach will bridge structures and processes on all scales, far beyond the capabilities of current theories and computer simulations. This will be achieved by targeting three key objec- tives: (i) Identification and quantification of flow and transport dynamics at the conduit scale. (ii) Characterization and modeling of karst network structure at the catchment scale. (iii) Derivation of a new upscaled approach to predict karst processes at different resolution scales. Together, this will result in an unprecedented multiscale modeling framework for the prediction of flow and transport in karst. Solving this long-standing problem is possible thanks to the synergy of the KARST PI team combining the set of skills and knowledge (hydrogeology, physics, mathematics) required to make a ground-breaking step in this field. Beyond that, the new approach is expected to impact other real-world systems in medicine (capillary networks), neuroscience (brain microcirculation) or glaciology (meltwater flow in glaciers).

Mots-clés : karst,networks,upscaling,flow,transport,graphs,structure,anomalous transport,continuous time random walks,lagrangian analysis,particle methods,dispersion,turbulent transport,groundwater,contamination,floods
Projet ERC : RECLESS (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université du Danemark du Sud — Pays : Danemark — Rôle : PI
Acronyme de l'entité : SDU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2185738.0 €

RECLESS will predict how ongoing ocean deoxygenation impacts microbial nitrogen transformations and thereby the future availability of nitrogen to support oceanic primary production and carbon sequestration. Microbial conversions of bioavailable nitrogen to dinitrogen in oxygen-depleted waters currently account for ~30% of the marine nitrogen loss, despite oxygen-depleted waters making up just 0.1% of the ocean volume. Models predict accelerating expansion of oxygen depletion, which entails increased nitrogen loss with negative impacts on ecosystem function and oceanic carbon sequestration, as well as an associated production of greenhouse-forcing nitrous oxide. However, biogeochemical ocean models currently fail to reproduce fundamental aspects of the microbial nitrogen transformations observed experimentally, including how nitrogen is either recycled or lost in oxygen-depleted waters. This reflects fundamental knowledge gaps concerning the environmental controls on growth, mortality, and activity of microbial populations, which preclude robust model predictions. RECLESS breaks new ground by synergistically integrating innovative oceanographic, biogeochemical, ecophysiological, and model-based investigations to close these gaps. With unprecedented in situ ecophysiological experiments using novel custom-made instrumentation as a cornerstone, RECLESS will identify key organisms, quantify their response to environmental controls, and construct the first comprehensive global microbial ecosystem model for oxygen-depleted marine systems. This model will enable robust predictions of how ocean deoxygenation affects nitrogen cycling and loss, greenhouse gas production, and interactions with the carbon cycle. Thus, RECLESS will transform our understanding of the present and future marine nitrogen cycle and its climate interactions, and set new standards for the integration of microbial processes in global biogeochemical analyses.

Mots-clés : marine nitrogen cycle,ocean deoxygenation,microbial ecophysiology,single cell activity,ecosystem modelling,ocean modelling
Projet ERC : MakingBlood (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Académie d'Åbo — Pays : Finlande — Rôle : PI
Acronyme de l'entité : Åbo Akademi University
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1232516.0 €

Life-saving blood cell replacement depends on voluntary donors. Availability is a challenge for specific groups, and 25% of patients needing blood stem cell transplants lack a compatible donor. The ideal alternative is clinical-scale production of Haematopoietic Stem Cells (HSC) from laboratory-maintained tissue-compatible sources, to provide an off-the-shelf source of blood cells. HSC are generated in the aorta/gonad/mesonephros region of the embryo, expand in the foetal liver, and are maintained in the bone marrow of adults. Current attempts to generate HSC in vitro do not consider the changing cellular, chemical, and physical characteristics of the different environments met by HSC in vivo from embryo to adult, and have been unable to reliably produce functional HSC. MakingBlood aims to establish a proof-of-concept platform for robust generation of human HSC from pluripotent stem cells by developing a self-organising gastruloid model of embryonic HSC generation without genetic manipulation, and successively recapitulating the natural foetal and adult HSC development environments. MakingBlood brings together an expert in HSC embryonic development, a national blood bank research director with expertise in adult HSC, an expert in molecular regulation of cell fate choices, and a bioengineer with expertise in mechanical and chemical integration for tissue production to deliver this breakthrough platform. By using state-of-the-art technology and multidisciplinary approaches, we will systematically detangle cellular, chemical, and physical properties of natural HSC generation, amplification and maintenance microenvironments, and iteratively identify essential elements that enable and promote HSC function. We will integrate key elements into modular scalable engineered niches to establish a HSC production platform, which can be developed as a bioreactor for on-demand blood production, and eventually replace donations as the clinical source of HSC and mature blood cells.

Mots-clés : gastruloids,engineered stem cell niches,mechanobiology,hematopoietic stem cells,developmental hematopoiesis
Projet ERC : PAAL (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université Radboud de Nimègue — Pays : Pays-Bas — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3886962.5 €

PAAL's objective is to investigate the interaction of phonological representations with cognisance, and their relationship to script. We view cognisance as part of the native speaker's core knowledge of their language.This includes generalisations about constraints on phonological representations in terms of features, size and shapes of morphemes, tone and metrical structures. Cognisance is not identical to the phonological representation of particular lexical items; rather, cognisance is the knowledge about what might be a conceivable word in a given language. We argue that cognisance is involved in all levels of language processing and change, in both spoken and written modalities. Speakers may have different vocabularies, but the phonological cognisance of individuals within a speech community should converge. It has been widely claimed that the notion of "phonological awareness" supports script acquisition. We propose that "phonological awareness" has to make sense in terms of cognisance, which is fundamental to all native speakers, regardless of their level of literacy. Novel to our approach is that it makes explicit predictions about the relationship between cognisance and representation and their relationship to script. Most scripts encode aspects of phonological structure but vary across languages and change over time. Even the closely related Germanic languages we primarily investigate, all using Latinate script, differ in their relationship between phonology and script. We compare the Latinate script to Bengali (also an Indo-European language) whose writing system is very different. Our working hypothesis is that phonological cognisance and representation govern spoken and written language processing, language acquisition, and change of all languages. In this interdisciplinary project, we combine expertise and methodologies across the fields of theoretical phonology, psycholinguistic and neurolinguistics, language acquisition, and language change.

Mots-clés : phonology,first language acquisition,language change,bilingualism,script,morphology,bengali,germanic
Projet ERC : UnMySt (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Fondation Jean-Marie Lehn — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1100000.0 €

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 : ClonEScape (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université technologique de Dresde — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TU Dresden
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1501125.0 €

Epithelial cancers are thought to evolve through a competitive process of mutation and selection in which the serial acquisition of oncogenic mutations confers an increasing fitness advantage, culminating in neoplastic transformation, tumour invasion, and metastasis. This programme often initiates through a phase of field cancerization in which mutant clones expand within the context of physiologically normal-looking tissue. To mitigate the risks associated with field cancerization, protection strategies have evolved that resist mutant clone expansion, from the development of anatomical features that limit clone growth to the activation of genetic and immunological surveillance mechanisms. Yet, despite these insights, our knowledge of how oncogenes act alone or in combination to evade these protection mechanisms to drive clonal pathogenesis remains largely unknown. Here, by combining a unique genetic lineage tracing strategy with comparative single-cell genomics and quantitative modelling-based methods, we will define the mechanisms that mediate mutant clone competition. By placing an emphasis on the squamous and columnar epithelia of the GI tract, we will investigate whether and how injury and inflammatory cues, as well as ageing, enable tumorigenic clones to evade natural protection strategies, functioning as a “second hit” in driving field cancerization and neoplastic transformation. Finally, to explore the translational relevance of our findings, we will combine DNA sequencing, single-cell methods, and spatial transcriptomics with the design and genetic manipulation of state-of-the-art 3D organ cultures to investigate mutant clone dynamics in human tissue. By tracing the origins of clonal pathogenesis, these findings promise insights into the design of new prevention, detection, and treatment strategies, targeting the early stages of cancer progression.

Mots-clés : intestine,stomach,oesophagus,liver,lineage tracing,mutant clone competition,injury induced cellular reprogramming,regeneration,cancer,ageing,advanced mouse genetics,human organoids,comparative single cell genomics,theoretical modelling
Projet ERC : CombaT7 (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Universitätsklinikum Hamburg-Eppendorf — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UKE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3191374.0 €

Bacteria interact with their environment via specialised secretion systems that deliver proteins outside of the cell. Due to a bias in research efforts, for many years such systems were assumed to be unique to Gram-negative bacteria. A major exception is the type VII secretion system (T7SS), which is widespread in Gram-positive bacteria and actinobacteria, including the important human pathogen Mycobacterium tuberculosis. The T7SS is a complex secretion apparatus that exports folded proteins and even protein complexes. While secreted substrates are well-known for being crucial players in host-pathogen interactions, our recent data indicate that specific substrates of the relevant opportunistic pathogen Mycobacterium abscessus and the fish pathogen Mycobacterium marinum are also involved in interbacterial antagonism. This makes T7SSs important factors to understand microbial interactions, also for the understudied part of the microbial world. While the mechanism of secretion via T7SSs remains little understood, our preliminary data show that not only their roles but also their substrates are more diverse than thus far thought. Here, we unite leading experts in microbiology, structural biology, cell biology, and biophysics to spearhead research on mycobacterial T7SSs and their roles in both interbacterial and host-pathogen interactions. In this unique consortium, we will (i) define the full trans-envelope T7SS by atomic force microscopy and cryo-electron microscopy, (ii) study the mechanism of transport by creating translocation intermediates, (iii) expand the set of T7SS substrates by extensive proteomics and bioinformatics analysis, and (iv) visualise the role of T7SS in bacterial warfare and host-pathogen interactions using microfluidics, innovative lung-on-a-chip infection models and time-lapse microscopy. This will deliver a deep mechanistic understanding of the diverse roles of mycobacterial T7SSs and provide clues to exploit these systems to combat infections.

Mots-clés : type vii secretion tuberculosis mycobacterium membrane complex toxin host pathogen interactions cryo electron tomography single particle analysis atomic force microscopy microfluidics time lapse microscopy
Projet ERC : ADDI (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université Toulouse Capitole — Pays : France — Rôle : Partner
Acronyme de l'entité : UT1
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 500000.0 €

The Advancing Digital Democratic Innovation (ADDI) project will pioneer the study of digitally augmented forms of civic participation for preference formation and elicitation. While digital technology has, for some time now, been widely seen as being in direct conflict with the needs of a well-functioning democracy, ADDI will realise the true potential of digital technologies in the democratic space. The project will be led by four well-known researchers with expertise in participatory platform design, deliberative democracy, and computational social choice. It will be organised around three methodological pillars - technology, empirics, and theory - and it will serve three core objectives: designing technologies and procedures for citizen deliberation and participation; experimentally testing the impact of digital platforms in deliberative and participatory forums; and understanding the structure of the preferences collected through digitally augmented instances of civic participation and deliberation. The technology track will lead the creation of interventions in the form of open-source platforms designed to digitally augment deliberation and participation. The empirical track will test these interventions using randomised trials in deliberative and participatory forums and will explore the statistical patterns of the preferences elicited in them. The theoretical track, finally, will contribute conceptual and algorithmic tools to elicit, present, and combine preferences in real-world environments, including situations where participants provide incomplete preferences and that involve under-represented minorities. At the end of the project, we will have charted the potential of digital technologies in supporting and improving democratic practices, while also providing a robust suite of scientifically validated open-source tools designed to distribute these capabilities at a global scale.

Mots-clés : computational social choice,collective intelligence,collective will formation