Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MetaDivide (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Groningue — Pays : Pays-Bas — Rôle : CO-PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Building a synthetic cell from molecular components is one of the grand scientific and intellectual challenges of the 21st century, and requires interdisciplinary skillsets to design and integrate biochemical modules at different levels of hierarchy. Great progress has been made in the fundamental understanding and reconstitution of key features, such as metabolic reaction networks and replication machinery. However, their successful synergistic integration in minimal cells still lags far behind, due to often largely different experimental approaches. MetaDivide will bring together two groups of world-leading scientists with complementary expertise in biochemistry and biophysics to address this gap. Poolman and Schwille will combine their mastery of membrane systems and protein machineries to establish a blueprint for coupling metabolic networks to cellular modules for spatiotemporal regulation and force-induction for division. By this, we aim to reconstitute in a minimal system one of the most stunning and central features of cellular life: The autonomous division of proto-cellular compartments by encapsulated self-organizing macromolecular machinery, driven by a self-sustaining energy metabolism. We will test our hypothesis that the otherwise separately researched features of life: Metabolism, Cell Division and Genome Segregation are mechanistically linked in the emergence of cellular life. Besides the great technical advance in synthetic biology, this will be a huge accomplishment in the understanding of biological mechanisms in today’s organisms, which in living cells are often obscured by their immense molecular complexity. Moreover, our new fundamental insights on the main principles underlying cellular life will advance application-driven research: By elucidating the mechanisms of out-of-equilibrium reaction networks and cell division, we will obtain insight that may inform the future development of generic small molecules to curb bacterial proliferation.

Mots-clés : bottom up construction of cells,membrane transport,cell division,physicochemical homeostasis,vesicles,membrane growth
Projet ERC : BATPROTECT (Horizon Europe, appel 2023, Synergy grants)
Entité participante : University Hospital Cologne — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2634355.0 €

The medical, financial, and emotional costs imposed by ageing and infectious diseases are major challenges for our societies. Strikingly, while past research has not provided solutions for extending human healthspan and preventing the harmful consequences of infections, nature has solved both problems in the only flying mammals – the bats. Among mammals, bats exhibit an exceptional longevity with little signs of age-related diseases. Despite being reservoirs for numerous deadly viruses, viral infections in bats are mostly asymptomatic due to unique immune system adaptations. The overarching goal of BATPROTECT is to achieve breakthroughs in our understanding of the molecular basis of bats’ extended healthspan and disease resistance to ultimately discover new directions to improve human healthspan and disease outcome. BATPROTECT integrates a team of world-leading experts in bat biology, genomics, immunology and gerontology to synergistically: (i) elucidate the molecular mechanisms that bats use to slow down expected ageing; (ii) identify the driving molecular mechanisms behind bats’ viral tolerance and limited age-related inflammation; (iii) uncover the genomic basis and evolution of extended healthspan and disease tolerance in bats; and, (iv) develop transgenic animal models to functionally validate the uncovered bat adaptations. We will generate 150 reference quality bat genomes, the novel immunological, bioinformatic, cellular and molecular tools required to take an integrative multi-omics approach and uncover the age and immune changes that occur in wild and captive bats across the ageing spectrum. We will identify the top regulators of longevity and immunity, using deep neural networks analyses, to functionally validate in our cellular systems and novel transgenic animal models- BatWorms and BatMice. Ultimately, we will provide a deeper understanding of extended healthspan and disease resistance and will pave the way for future therapeutics.

Mots-clés : bat biology,healthy ageing,antiviral responses,c elegans,genome sequencing,comparative gerontology,wildlife immunology,multi omics,ecology,evolution
Projet ERC : CoTransComplex (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Nederlandse organisatie voor wetenschappelijk onderzoek — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NWO
Type d'entité : Recherche
Financement ERC de l'entité : 3286188.0 €

Most proteins function within larger complexes. How these intricate structures are correctly formed is poorly understood, yet critical to all cellular processes and pathological conditions. Recent breakthroughs suggest that multi-protein complexes form co-translationally, by super-assemblies of multiple ribosomes and other cofactors that are coordinated in time and space. This striking notion contrasts starkly with textbook models and is key to the possibilities and failures of complex formation. However, owing to technical limitations, the mechanisms and scope of actively coordinated protein assembly are poorly understood. Elucidating how these large and transient co-translational formations produce protein complexes throughout the genome is a next-level challenge that cannot be addressed by a single discipline. We propose a unique merging of cutting-edge approaches: 1) Ribosomal profiling to detect interactions between ribosomes engaged in assembly and cofactors genome-wide, 2) Single-molecule force spectroscopy and super-resolution imaging to reveal ribosome movements and nascent chain assembly. 3) Cryo-EM and tomography to elucidate the structural basis of ribosome interactions that enable direct assembly. Our program addresses 1) the coordination of multiple ribosomes in time and space, 2) the folding and assembly of nascent chains, and guidance by chaperones and novel cofactors, 3) the major protein complexes classes of homo-dimers, higher-order oligomers, hetero-dimers, and complexes formed at membranes. This ambitious program will provide insight of unprecedented detail and scope, spanning from the cellular to the atomic level, from in vivo to in vitro, from genome-wide patterns to molecular mechanisms, and from bacteria to human cells. It will impact a vast spectrum of protein complexes, reveal unknown layers of control in protein biogenesis, with implications for ribosome quality control, artificial protein design, and mechanisms of disease.

Mots-clés : co translational protein folding and assembly,translation,ribosomes,chaperones,cryo em,single molecule biophysics,ribosome profiling
Projet ERC : CoTransComplex (Horizon Europe, appel 2022, Synergy grants)
Entité participante : École polytechnique fédérale de Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3034116.0 €

Most proteins function within larger complexes. How these intricate structures are correctly formed is poorly understood, yet critical to all cellular processes and pathological conditions. Recent breakthroughs suggest that multi-protein complexes form co-translationally, by super-assemblies of multiple ribosomes and other cofactors that are coordinated in time and space. This striking notion contrasts starkly with textbook models and is key to the possibilities and failures of complex formation. However, owing to technical limitations, the mechanisms and scope of actively coordinated protein assembly are poorly understood. Elucidating how these large and transient co-translational formations produce protein complexes throughout the genome is a next-level challenge that cannot be addressed by a single discipline. We propose a unique merging of cutting-edge approaches: 1) Ribosomal profiling to detect interactions between ribosomes engaged in assembly and cofactors genome-wide, 2) Single-molecule force spectroscopy and super-resolution imaging to reveal ribosome movements and nascent chain assembly. 3) Cryo-EM and tomography to elucidate the structural basis of ribosome interactions that enable direct assembly. Our program addresses 1) the coordination of multiple ribosomes in time and space, 2) the folding and assembly of nascent chains, and guidance by chaperones and novel cofactors, 3) the major protein complexes classes of homo-dimers, higher-order oligomers, hetero-dimers, and complexes formed at membranes. This ambitious program will provide insight of unprecedented detail and scope, spanning from the cellular to the atomic level, from in vivo to in vitro, from genome-wide patterns to molecular mechanisms, and from bacteria to human cells. It will impact a vast spectrum of protein complexes, reveal unknown layers of control in protein biogenesis, with implications for ribosome quality control, artificial protein design, and mechanisms of disease.

Mots-clés : co translational protein folding and assembly,translation,ribosomes,chaperones,cryo em,single molecule biophysics,ribosome profiling
Projet ERC : HYROPE (Horizon Europe, appel 2023, Synergy grants)
Entité participante : École polytechnique fédérale de Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3195074.15 €

HYROPE proposes to combine unique, fundamental skills of four European laboratories to perform atmospheric and high-pressure experiments coupled to high-performance simulations of an innovative concept for gas turbines to burn zero-carbon, hydrogen-based fuels. Due to their high-power density, it would be a potential game-changing technology that can deliver energy on demand for both power and aviation. Gas turbine technology has evolved from an abundance of hydrocarbon fossil fuels but has the unique potential to be fuel flexible and burn renewable, zero-carbon hydrogen-based fuels such as hydrogen or ammonia. However, these fuels raise several fundamental issues as they have very different combustion properties and emission properties when compared to hydrocarbon fuels. Hydrogen is highly diffusive, extremely reactive, and its turbulent burning rate exhibits an unexplained strong pressure dependence. Predicting whether hydrogen flames that are stable at atmospheric pressure will be stable at higher pressures, as needed in gas turbines, remains an unsolved fundamental problem. Ammonia is a convenient hydrogen carrier that can be partially decomposed to hydrogen but requires careful control of NOx emissions. How to handle the effects of pressure on these fuels is a major gap in our scientific knowledge. HYROPE will study the effects of pressure on the combustion of hydrogen-based fuels in a fuel flexible, staged combustion approach where the first stage is controlled by flame propagation and the second one by autoignition. This configuration offers enormous potential that has not yet been exploited for such fuels. This can only be achieved through a joint work combining state-of-the-art tools, from novel experimental facilities at high pressures, advanced optical diagnostics to high-performance computing. The project will accelerate the development of new, high-power density, fuel-flexible combustion systems and unleash the potential of zero-carbon gas turbines.

Mots-clés : hydrogen,thermal power,zero carbon fuels,power generation,gas turbine
Projet ERC : MechVivo (Horizon Europe, appel 2024, Synergy grants)
Entité participante : École polytechnique fédérale de Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3113696.75 €

Computational biomechanics is a fast-growing area of science. However, many of its fruits have not yet been translated into clinical practice. The main barrier to the translation of computational biomechanics into clinics is the lack of information about patient-specific mechanical properties of biological tissues. There are some methods for partially assessing these properties, but they have substantial limitations. A major cause of these limitations is the operating principle of current approaches, which rely on the analysis of the response of a tissue to some form of mechanical loading in vivo. To overcome this bottleneck, we propose a paradigm change. We will develop a method to infer mechanical properties of soft biological tissues in vivo based on a fundamentally new operating principle. To this end, we will leverage the synergy of three scientific areas covered by the three principal investigators of this project: (i) magnetic resonance imaging (MRI), (ii) experimental biomechanics, and (iii) physics-informed machine learning. Specifically, we will develop a new type of subvoxel MRI relaxometry to probe tissue microstructure non-invasively and establish a combined experimental and computational framework that will uncover for the first time the mechanistic link between transcriptomics, microstructure, and mechanical properties of soft biological tissues in a detailed manner. By leveraging this information with novel physics-informed machine learning techniques, we will gain the ability to determine the mechanical properties of soft tissues from clinical MRI data and blood samples with unprecedented accuracy and completeness. Our approach will be a crucial steppingstone to translate biomechanical computational models into clinical practice at a large scale. As a proof of concept, we will demonstrate how our new method can support the diagnosis of heart failure with preserved ejection fraction (HFpEF), one of the most common causes of mortality and morbidity.

Mots-clés : biomechanics,solid mechanics,materials modeling,soft tissue biomechanics
Projet ERC : CHIRAL-PRO (Horizon Europe, appel 2024, Synergy grants)
Entité participante : Université de Vigo — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1123700.0 €

Chirality, or the absence of mirror symmetry, is omnipresent in both biological and abiological forms of matter. Rapid progress has recently been achieved in the synthesis of chiral inorganic nanoparticles (NPs), of great interest because of the giant optical activity observed in individual NPs and their assemblies. Such nanostructures yield chiral features at multiple length scales, resulting in a huge diversity of chiral morphologies. The field is expanding toward connecting chirality across the worlds of nano and bio, linking optical and biological chiral functionalities. However, what is currently hampering real-world applications is the step from intuitive synthesis of chiral nanostructures to a purposeful design for specific interactions with biological components. The main objective of CHIRAL-PRO is to develop a widely applicable methodology to design chiral NPs with exceptional optical activity, for strong and predictable enantioselective interactions with nanoscale biological entities, such as proteins and amyloid fibrils. The fundamental understanding of the role of chirality in the recognition between inorganic and biological chiral structures will be used for the programmed assembly into optically active nanofibers and for case studies in sensing and metamaterials. To reach this ambitious goal, the complementary expertise of all three partners involved will be essential: synthesis and assembly of chiral plasmonic NPs (Liz-Marzán); three-dimensional electron microscopy of NPs, and the visualization of their interactions with biomolecules in liquid (Bals); and self-assembly methods and computational predictions for chiral multiscale interactions (Kotov).  In addition to groundbreaking advancements in fundamental research, the high gain of this work can be found in the generation of a toolbox enabling the scientific community to shift from guessing to precise design of chiral nanostructures with predefined properties.

Mots-clés : nanoparticle synthesis,chirality,metal nanoparticles,nanoplasmonics,nanoparticle assemblies,transmission electron microscopy,electron tomography,predictive machine learning,nanoparticle protein interactions,protein detection
Projet ERC : BREAKDANCE (Horizon Europe, appel 2022, Synergy grants)
Entité participante : Centro de Regulación Genómica — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG
Type d'entité : Recherche
Financement ERC de l'entité : 356756.0 €

Understanding the establishment of an animal body plan is an important challenge of modern biology. Progress has been mainly limited by (1) a separation of research fields studying genetic and biophysical mechanisms, and (2) a lack of approaches to mimic multicellular tissue organization from first principles. In a cross- disciplinary effort, we will focus on the earliest stages of animal development, when first steps of cell differentiation define the primary body axis through spatial symmetry breaking, laying the foundation for the future body plan. Our goal is to identify the fundamental mechanisms controlling this symmetry breaking process. To this end, we will study in detail the interplay between global tissue geometry (shape, size, and dimension), physical boundary conditions, and mechano-chemical cell interactions. Therefore, we address the following questions: (i) How do global shape and size control local cellular states and interactions? (ii) How do local cellular states and interactions induce robust symmetry breaking at the tissue level? (iii) To which extent can geometry control cell fate specification in a species-independent manner? To overcome previous limitations, we will establish a comprehensive methodological toolbox of synthetic bottom-up approaches and functional ex-vivo assays. We use as model systems mouse, zebrafish, and later also human embryonic stem cells. This will be combined with advanced biophysical techniques and theoretical modeling in order to systematically dissect the mutual couplings between genetic patterning mechanisms and morphogenetic processes, thereby revealing the multicellular dance underlying tissue symmetry breaking. Our results will shed new light on the long-standing question of how complex biological forms are robustly built from a single fertilized egg, impacting on our understanding of organism development and maintenance, and opening new directions for the controlled design of artificial tissues and organs.

Mots-clés : biological self organization,tissue patterning,quantitative approaches to mechano chemical signalling,cell and tissue mechanics,size and shape in biology
Projet ERC : CARAMEL (Horizon Europe, appel 2025, Synergy grants)
Entité participante : Université de Berne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : Unibe
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2487568.0 €

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 : MIDRASH (Horizon Europe, appel 2022, Synergy grants)
Entité participante : École pratique des hautes études — Pays : France — Rôle : CO-PI
Acronyme de l'entité : EPHE PSL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 4404837.5 €

MIDRASH aims to construct a groundbreaking interdisciplinary methodology for a global approach to the study of the treasure trove of medieval literary manuscripts in Hebrew script. Jews produced and consumed a prodigious cornucopia of texts in Hebrew, Aramaic, Judeo-Arabic and other vernacular languages, intertextually closely related like a mille feuille. The manuscripts constitute the unique remains of medieval Jewish literary culture, having survived - and witnessing to - centuries of migrations, persecutions and censorship. With the recent digitization of the extant manuscripts and with contemporary advances in computer vision, natural language processing and machine learning, the time is ripe for broad new studies into this manuscript culture. We can now study questions regarding their materiality, textuality, transmission and historical contexts on an unprecedented scale or heretofore beyond reach.  MIDRASH proposes a pioneering study of the extensive corpora of: (1) biblical manuscripts; (2) Midrash (late antique exegetical and homiletical commentary on the Bible); (3) medieval commentaries of the Bible and Mishnah; and (4) liturgical manuscripts. Only a small fraction have been transcribed, let alone studied. State-of-the-art and bespoke algorithms will be applied to resolve issues of reading order, code switching, and transcription errors. Once mechanically transcribed, known and unknown works will be identified and reconstructed and multilingual intertextualities discerned. The latest fine-grained paleographical techniques and trained neural networks will be brought to bear on questions of provenance and transmission. Philological methods and computational linguistics will be applied to questions of textual fluidity and evolution to further our knowledge of the production and transmission of Hebrew manuscripts and texts, their authors, scribes and readers, and enhance their role as the pivotal aspect of European and Mediterranean intellectual history.

Mots-clés : hebrew manuscripts,document analysis,nlp,computer vision,midrash