Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : pro2neo-RUBISCO (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems E ngineering
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 : 2837483.0 €

Can we re-construct the engine of natural CO2-fixation? Rubisco catalyzes the key reaction in photosynthesis: the capture and conversion of atmospheric CO2 into biomass. However, despite billions of years of evolution the enzyme is (still) constrained by a trade-off between CO2-fixation activity and CO2-specificity, which limits photosynthetic carbon capture, and thus directly agricultural yield. In pro2neo-RUBISCO, we will overcome this fundamental limitation of photosynthetic CO2-fixation with a completely fresh approach. We will use an evolutionary-synthetic biology strategy to study the evolutionary history of Rubisco, derive a molecular understanding for the enzyme’s mechanism, and develop highly efficient, new-to-nature solutions that we will validate in a real-world context: the living chloroplast. We will use ancestral reconstruction to replay crucial steps in the evolutionary history of the enzyme. We will resurrect the very first scaffolds that just learned to fix CO2 (“proto-Rubiscos”), and study Rubisco ancestors that started to loosely interact with an accessory small subunit. We will re-evolve these ancestral enzymes and provide them with artificial small subunits to open up new evolutionary paths leading to improved variants. These (r)evolutionary studies will be complemented by synthetic biology efforts: We will liberate Rubisco from its entropic constraints by separating the complex multi-step reaction onto different proteins that work in tandem, and go even one step further by re-inventing the enzyme’s scaffold, finding a new home for the Rubisco reaction and create a truly ”neo-Rubisco”.  Compared to many efforts in the field, pro2neo-RUBISCO does not screen for existing Rubiscos with improved kinetics or improving existing Rubiscos. In pro2neo-RUBISCO, we aim at (re)exploring the history and evolutionary landscape of Rubisco, and delivering completely novel architectures for the key driver of the global carbon cycle.

Mots-clés : synthetic biology,co2,carboxylase,co2 fixation,metabolic engineering,rubisco
Projet ERC : TranslAtWar (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Nantes Université — Pays : France — Rôle : PI
Acronyme de l'entité : NU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2128708.0 €

While the history of translation is a field in Humanities that has known a significant increase recently worldwide, a European history of literary translation during the war has yet to be written. Due to the importance of power relations, ideology, censorship and propaganda, the practice of literary translation and European translators in wartime is a particularly interesting configuration, but it remained relatively unexplored so far on a truly European level: few comprehensive researches have been carried out on literary translation in Europe during this constrained historical context, unlike on translation practices during peacetime. What was translated (how and by whom) whilst wars were destroying bonds between people and States? What meaning does one then invest translation with? Focussing on World War 2, a very significant period of 20th century European history, the TranslAtWar (Literary Translations at War) research project aims at investigating how literary translation then contributed to the understanding of History in the making, and, reciprocally, how History contributed to the analysis of multiple forms of literary translation. It is about questioning the circulation of ideas and culture through translation, and equally taking a close interest in the role of the agents of these circulations, both male and female translators, during wartime. We will also question the impact that the practice of translation in such exceptional historical circumstances had on the intellectual and cultural development of several countries, and what it is likely to have contributed given their position (central or peripheral) in the world of European literature. Under my supervision and taking advantage of long-standing international partnerships and expertise, this innovative project aims at writing a new page of European history and, eventually, promoting the emergence of a new disciplinary field at the crossroads of translation studies and war studies.

Mots-clés : literary translation,translators,translation history,literature,world war 2 ww2,europe,propaganda,censorship,ideology,cultural transfers
Projet ERC : Nab-Heart (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université de Pavie — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2250000.0 €

In cardiac cells, kinase enzymes are key modulators of calcium homeostasis, mitochondrial function, excitation-contraction coupling, and metabolism. Of these, the delta isoform of Ca 2+ /Calmodulin-dependent kinase (Camk2d) is particularly relevant to the induction of life-threatening cardiac arrhythmias.Of the several promising small molecule and peptide Camk2d inhibitors proposed in pre-clinical investigations, none has entered clinical applications. The severity of side effects, a well-known issue for kinase inhibitors, in this case is further amplified by the high homology and the unique Ca 2+ -dependent regulatory physiology among four Camk2 isoforms, plus the delicate role of the ubiquitously expressed Camk2d in non-cardiac tissues. Since the major obstacle to developing a cardio-specific, Camk2d-specific inhibitor mainly relies on reaching high isoform selectivity, the Nab-Heart project will conjugate selected Nanobodies (Nbs) to a new Camk2 inhibitory peptide to develop the first selective kinase inhibitor. Such a molecule will prevent the development of life-threatening arrhythmias in a variety of cardiac conditions, spanning from inherited arrhythmias such as Long QT Syndrome to acquired and highly prevalent diseases such as atrial fibrillation and heart failure. The team will identify Nb candidates with the desired Camk2d isoform-selectivity and affinity. Optimized substrate-mimicking Camk2d-inhibitory peptides will be covalently linked to the selected Nbs (Nb-inibs) to ensure delivery of the inhibitory module to the pathologically active Camk2d target with outstanding selectivity and affinity. The strategy will be validated in vivo through cardio-specific AAV9 delivery of the Nb-inib candidates in a mouse model of Catecholaminergic Polymorphic Ventricular Tachycardia and in a Swine model of acquired heart failure, where Camk2d is known to be the trigger of life-threatening arrhythmias.
Projet ERC : CLONAL (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Cell Biology, Development, Stem Cells and R egeneration
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 : 2477005.0 €

Clonal reproduction provides certain seed plants with the opportunity to spawn large numbers of clonal individuals in the absence of fertilization. Root sucker formation is a mechanism by which somatic cells of the root spontaneously change their developmental path and give rise to hundreds of clonal offspring. This trait is understudied owing to the scarcity of systems where genetics and advanced imaging can be employed for in-depth studies. Here, I propose to address this problem by developing a diploid Cardamine species as a powerful experimental system for this purpose. This species reproduces not only sexually, but also asexually via root suckers. How root suckers form and how the plant determines the balance between sexual and asexual reproduction is unknown. Close relatives include Arabidopsis thaliana, the best-characterized plant genetic system, and Cardamine hirsuta, a model system that we developed for comparative studies. Yet, neither of these two species form root suckers. I propose to leverage this difference between closely related species to elucidate, at single-cell level, the molecular genetic basis for root sucker development. To jump-start this work, I have in place a genome assembly, genetic transformation and resources for forward and reverse genetics approaches. I will also take advantage of intra-specific natural variation to identify the genetic basis for root sucker diversity and the basis for trade-offs between sexual and asexual reproduction. Ultimately, I aim to reconstruct the root sucker trait from its constituent genetic elements, and transfer it between species. Overall, I will deliver one of the most advanced studies in complex eukaryotes on the genetic basis for development and diversity of clonality – a key trait with significant effects on life history. I will also produce a wealth of resources for the community to further exploit this novel model system.

Mots-clés : plant development,asexual reproduction
Projet ERC : PROTECT (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 2498719.0 €

During healthy aging but also in osteoporosis, a disease that affects more than 22% of European women beyond the age of 50, loss of mineralized bone is caused by a disbalance between bone formation and resorption. While blood vessels are abundant in the skeletal system and play essential roles, they are currently not considered in the context of anti-osteoporosis therapy. Moreover, apart from the role of sex hormones, we know too little about the impact of sex-specific regulators in physiological and disturbed bone homeostasis. Our recent work has provided fundamental insights into the organization of the bone vasculature in mouse, the heterogeneity and functional specialization of endothelial cells (ECs), and the changes during aging. Recent and unpublished research from my team has utilized single cell RNA sequencing in combination with advanced immunostaining and imaging to identify a novel EC subpopulation (termed type R for remodeling). Type R vessels are post-arterial capillaries found at sites of homeostatic and therapeutic bone turnover, mainly trabecular bone, and their activation in young mice can enhance osteogenesis. In aging mice type R vessel clusters emerge inside cortical bone at sites of bone loss. PROTECT will systemically characterize the function of ECs and, in particular, type R capillaries in healthy homeostasis and during bone loss. This will involve the generation of new mouse lines for intersectional genetics and the characterization of critical molecular regulators. We will also characterize sex-specific and age-related factors controlling bone homeostasis and employ approaches to translate our findings into the human system. Preclinical experiments in mice will establish whether ECs and type R capillaries are involved in the response to therapies aiming at osteoblasts or osteoclasts. PROTECT will generate the conceptual basis for future approaches utilizing endothelial cells for the prevention of bone loss and anti-osteoporotic therapy.

Mots-clés : bone,osteogenesis,osteoblasts,osteoclasts,blood vessels,vascular,endothelial cells,mouse
Projet ERC : LPS-CODE (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université de Naples - Frédéric-II — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

The lipopolysaccharide endotoxins (LPSs) are ubiquitous microbial cell surface glycolipids of Gram-negative bacteria and are key molecular actors in the interaction with eukaryotic hosts. Traditionally, studies have focused on the role of LPS as dangerous and potent molecules with the ability to boost innate immunity in eukaryotes and cause sepsis in humans and severe pathologies in plants. In recent years, however, it has become clear that LPS is not always working as a microbial weapon. Indeed, LPS also covers the surface of symbiotic and beneficial bacteria. However, a precise chemical and molecular information on this duality remains elusive. Two central questions remain unsolved with the required chemical precision: i) which are the key features of the molecular interactions between LPSs and the host receptors; ii) how the subsequent signalling pathways lead to either pathogenicity or symbiosis in mammals and in plants. Indeed, despite the harmful image of LPS, disentangling these features of LPS chemistry could inspire new avenues for the employment of LPS and LPS-like molecules as a novel generation of therapeutics in medicine and agriculture. Thus, the key objective of LPS-CODE is to unravel the key features of the molecular interactions between LPS and the host receptors and decipher the subsequent signalling pathways in both animals and plants. This will be achieved by identifying the key microdomains within the LPS molecules that establish beneficial or detrimental interactions with the host, eventually driving elicitation or suppression of host innate immunity. LPS-CODE is grounded on (bio)-organic chemistry and chemical biology, with strong emphasis on glycan chemistry and structural glycosciences to decode the microbial language and thus decipher the chemical epitopes common to either all “friendly” or pathogenic LPS in the interaction with both plants and animals. With this, we will finally be able to make the conceptual leap to conceive new molec

Mots-clés : carbohydrates,lipopolysaccharides,structural glycoscience
Projet ERC : TRANSFORMERS (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : GEOMAR Helmholtz Centre for Ocean Research Kiel — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : IFM-GEOMAR
Type d'entité : Recherche
Financement ERC de l'entité : 2864427.5 €

The plate tectonic revolution gave birth to three types of plate boundaries; two got most of the interest, i.e., the mid-ocean ridges where new ocean floor is formed and subduction zones where the lithosphere is recycled back into the Earth’s interior. In the oceans, the third type, the “simple” strike-slip conservative plate boundary or oceanic transform fault (OTF), was treated like an orphan in a Charles Dickens novel. However, recent observations challenge plate tectonics, revealing that OTFs show unexpected complex behaviour. The morphology of oceanic transform systems and numerical modelling suggests that OTFs are extensional below their strike-slip faults at the surface. Later in their evolution, before converting from an active fault into an inactive fracture zone at the ridge-transform intersection, OTFs may turn into accretionary features. Yet, how can a strike-slip plate boundary, generating magnitude >7 earthquakes, promote extension forming up to 18 km wide and 7 km deep valleys? Furthermore, a fault zone grading from a strike slip fault into an extensional feature at depth would be a unique geological feature and may control their major seismic slip deficit. TRANSFORMERS will reveal: (i) if OTFs are indeed wrongly classified in plate tectonics and are not conservative plate boundaries, but instead have to be re-classified as features where accretion occurs in two-stages, separated by a period of transform extension, revealing a process fundamentally different from predictions of plate tectonics, suggesting that fracture zones are structurally different from OTFs; (ii) how OTFs operate from top to bottom and why their seismic moment release is too low. The project will require major sea-going efforts, issuing seismological, geodetic and geological surveys on the ocean floor, mimicking a multiple year’s land campaign. The outcome will revolutionize our understanding of oceanic transform faults, adding a new chapter to plate tectonics.

Mots-clés : plate tectonics,oceanic transform faults,seismic slip deficit,seismicity,crustal structure,depth dependent deformation,depth dependent temperature,hydrothermal activity,hydration
Projet ERC : ION-FLUX (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
Entité participante : Armagh Observatory & Planetarium — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : AOP
Type d'entité : Recherche
Financement ERC de l'entité : 1954500.0 €

Now that JWST has been launched, the Early Universe is finally opening up. What has already transpired is that we do not understand star formation at high redshift. Furthermore, with the emergence of gravitational waves, surprisingly heavy black holes have been revealed, even in previous "forbidden" mass zones. What is crucial to make progress is a massive-star framework that works Locally and can be applied to the distant Universe -- allowing to test my hypothesis that very massive stars (VMS) re-ionised it. Today, such a framework does not exist. One of the reasons is that historically observations of massive stars have been rare, but with the emergence of large spectroscopic datasets, such as XShootU (PI: Vink), the physics dominating massive stars can finally be revealed. Moreover, I have recently made theoretical breakthroughs in wind mass loss (that sets the ionising flux), as well as a wind envelope interaction mechanism underlying luminous blue variables and supernova progenitors. In ION-FLUX, I propose a fundamentally new approach that combines my unique expertise in observations as well as stellar evolutionary, atmospheric, and wind theory. We have now implemented my mass-loss kink to evolutionary models, revealing that VMS do not evolve horizontally in the Hertzsprung-Russell diagram as canonical OB-type stars do, but vertically. Moreover, VMS are shown to completely "evaporate" owing to their strong metallicity-dependent winds, providing a preference for black-hole formation over pair instability supernovae, at least Locally. In parallel, Helium II emission from these VMS has now been included in population synthesis models, confirming that it is the VMS that are the likely culprits for this puzzling emission in star-forming galaxies. My innovative approach of forward - backwards modelling -- simultaneously benchmarking my models to new spectroscopic survey data -will culminate in a framework that correctly links star formation Near and Far.

Mots-clés : massive stars,stellar winds,mass loss,stellar evolution,reionisation,black holes,supernovae
Projet ERC : INSITUFOLD (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: B iological  Mechanisms , Structures  and Functions
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 : 2136875.0 €

Molecular chaperones mediate protein folding and conformational maintenance. Failure of these fundamental cellular functions results in a breakdown of protein homeostasis (proteostasis) and facilitates the manifestation of diseases associated with protein aggregation. Much progress has been made in understanding the mechanisms of individual chaperone systems, such as the Hsp70s and the chaperonins, based on analyses in vitro. How these machineries function in the intact cell is not well understood, however. The goal of this proposal is to observe and characterize the dynamic action of the major chaperone systems and their interplay in intact cells in real time.Using live cell single molecule imaging combined with biochemical analyses, proteomic profiling, and genetic screening, we will address the following questions: i) How does the chaperone machinery assist protein chains during and after translation to achieve folding and assembly? We will develop single particle tracking to monitor the chaperone engagement of nascent chains in situ in mammalian cells. ii) How is the conformational stability of chaperone clients assessed, maintained and triaged in healthy cells and in cells burdened with pathological aggregates? We will track the interactions of metastable proteins with chaperones and proteolytic machinery. iii) What is the efficiency of protein folding across the proteome under normal conditions and in chaperone-deficient cells? Pulse proteolysis/mass spectrometry will be developed to analyze the folding of nascent polypeptides and will be scaled to analyze the entire proteome of different cell types. By depleting specific proteostasis components we will explore the capacity of the chaperone network for compensatory rewiring and identify vulnerable proteins with an obligate chaperone dependence. Overall, this work will employ new technology to advance our understanding of the chaperone system in protein folding and proteome maintenance at the cellular level.

Mots-clés : protein folding,molecular chaperones
Projet ERC : DiverseSynapse (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 2498575.0 €

Synapses differ in their shape, size, and function and exhibit ongoing plasticity during the development and modification of neural circuits. The structural diversity of synapses is largely known whereas the molecular diversity of synapses is much less well understood. While most synaptic molecules have been identified by immunolabeling and bulk proteomic approaches, the complement of proteins present at individual synapse types, as well as their stoichiometric relationships with other molecules remains unknown. Indeed, our current classification mostly relies on neurotransmitter/receptor phenotypes, leading to broad descriptors like “excitatory” or “inhibitory” synapses. Because the function of the synapse, as well as its ability to change, is largely determined by the quality and quantity of molecules that inhabit it, it is essential to understand synaptic molecular diversity. The aims of this proposal are to determine the proteomes and transcriptomes of genetically-identifiable synaptic populations in different brain areas and to determine the molecular diversity in these same synapse populations using transcriptomic analysis of individual synapses. We will also assess how these synaptic proteomes, transcriptomes and the transcriptomic diversity respond to plasticity. To study synaptic proteomes and transcriptomes we will use Fluorescence-Activated Synaptosome Sorting to purify different synaptic populations (excitatory, inhibitory, dopaminergic) from different brain areas. We will use the state-of-the-art methods optimized for quantitative transcriptomic and proteomic profiling of very small amounts of sorted synapses and develop a method, SynDrops, for the transcriptomic analysis of individual synapses. We will examine how synaptic proteomes and transcriptomes change during plasticity. These studies will reveal the landscape of synaptic diversity within synapse types and across brain areas and allow the field to probe “diseased” synapses in the future.

Mots-clés : synapse,proteomic,transcriptomic,local protein synthesis,mrna trafficking,mrna localisation