Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Immuno-mechanics (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Hôpital universitaire de la Charité de Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : Charité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2490725.0 €

Both scar formation and restitutio ad integrum during bone regeneration rely on cellular self-organisation that involve cell contraction and fibronectin/collagen formation. This early stage of cellular self-organization is later followed by angiogenesis and mineralisation. Scar-free regeneration of physiological tissue homeostasis requires balanced downregulation of early inflammation, however little is understood of the immune-mechanical coupling involved. We aim to lay the foundation for reducing patient suffering resulting from scarring by combining two distinct scientific worlds, for which we have been a major driving force: the distinct regulation of local inflammation and the mechano-biology during regeneration. By combining both of our areas of expertise, we aim to harvest the potential of the novel cross-disciplinary field Immuno-Mechanics. This ambitious project concentrates first on identifing the different mechanical niches that immune cells experience early in successful healing and non-healing. Second, we will engineer synthetic niches to control fibroblasts and fibroblast-immune cell interactions to steer cell self-organisation and matrix formation in vitro. Third, we plan to verify that these synthetic niches reprogram hematoma composition and can thus reduce later scarring in vivo. The proposed experiments are challenging as they have never been done this way before, but are feasible since they capitalise on our strengths in osteo-immunology and mechano-biology. Novel technologies will be combined in a unique way to engineer the immune-mechanical cell niche, to passivate activated immune cells and to reprogramme cell fate. This will allow us to substantially advance the basic understanding of the interplay between immune cells and their mechanical niche during early regeneration. By harnessing the mechanisms of the immune-mechanics interplay, we will lay the foundation for advancing immune-modulatory therapies to reduce harmful scarring.

Mots-clés : mechano biology,bone healing,regeneration,cell matrix interactions
Projet ERC : PRECISION SMOM (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université de St Andrews — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 436807.5 €

Fast and efficient solution-based homogeneous catalysis, or the synthesis of complexes with weakly bound ligands (e.g. methane), often requires the formation of a highly active, coordinatively unsaturated, metal centre. However, the vast excess of solvent can play a detrimental role by competitive coordination, or reaction itself, at the metal centre. Even if solvent does not impede the formation of reactive species, dimerisation can form inactive complexes. These factors quench reactivity and obstruct the formation of reactive complexes that are on the brink of stability, but at the cutting-edge of synthesis and catalysis.  If the problem is the solution, then the solution is to remove the solution!  PRECISION SMOM directly addresses this problem, redefining what is possible in the molecular synthesis of, and catalysis with, highly active organometallic complexes, by offering opportunities in chemical space that extend far beyond what is possible using solution-based methods. It does this by exploiting the Solid-state Molecular OrganoMetallic (SMOM) methods pioneered by Weller; where synthesis, reactivity and catalysis occur in crystallo using precisely-defined molecular single-crystals in solid/gas processes, as shown by the synthesis and reactivity of stable σ-alkane complexes, solving a 40-yr-old challenge in organometallic chemistry.  PRECISION SMOM will use a suite of synergistic studies to understand, and control, the influence of metal site and microenvironment on in crystallo reactivity. Such holistic, fundamental, understanding will promote the translation of SMOM systems into precisely-defined heterogeneous molecular catalysis, focussing on selective and efficient processes for a range of challenging but widely applicable transformations. PRECISION SMOM will change the way we think about reactivity in molecular single-crystals: breaking new ground, embracing wider challenges, and exploiting new opportunities for in crystallo synthesis and catalysis.

Mots-clés : single crystal to single crystal molecular synthesis and catalysis
Projet ERC : MetaChange (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental B iology, Ecology  and E volution
Entité participante : Université de St Andrews — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 125000.0 €

Despite connections between metacommunity level processes that maintain biodiversity and anthropogenic pressures that erode those processes, these have not been well integrated. I propose a multifaceted approach that (1) builds on metacommunity theory to develop expectations for the influence of anthropogenic drivers on scale-explicit biodiversity change; (2) uses this theory to develop an analytical pipeline to disentangle local and landscape factors driving this change; (3) use the derived results to develop scale-explicit projections of future biodiversity change that can aide biodiversity policy decisions.  With theoretical expectations and analytical procedures in hand, we will synthesize biodiversity change across scales, and the relative influence of local versus landscape-level drivers on those changes. We will apply our analytical pipeline to the largest compilation of metacommunity time series to provide a comprehensive analysis of biodiversity change. We will complement this with a data collection campaign to ‘resurvey’ zooplankton metacommunities from ponds that had been surveyed 10-50 years previously, but which have experienced different levels of background ‘change’ (e.g., loss of nearby habitat). We will also compile a database to explore the potential influence of habitat restoration via local and landscape processes, and its influence on scale-explicit biodiversity change. We will analyse these synthetic datasets together with geospatial driver data using our novel analytical pipeline. Finally, we will develop a unique pipeline integrating metacomunity theory with our synthetic results and machine learning to develop projections of biodiversity change in the face of scenarios of anthropogenic change. With the information gained, we will contribute not only to a better understanding of the most important feature of life on this planet—its biodiversity—but by developing this understanding, we can provide an avenue to mitigate the changes.

Mots-clés : metacommunity theory,synthesis,restoration,land use,habitat loss,dispersal limitation,resurvey,pond,wetland,forest,grassland
Projet ERC : EUCLIDEAN (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université Vie-Santé Saint-Raphaël — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

This proposal aims to investigate the development of dysfunctional adaptive immune cells during chronic hepatitis B virus (HBV) infection and to develop new strategies to reprogram them into functional cells with potent antiviral activity. Our hypothesis, based on extensive preliminary data, is that HBV induces a unique type of adaptive immune cell dysfunction that differs from that observed in other viral infections or cancer. To investigate this, we will use unique mouse models of HBV pathogenesis, several of which have been generated ad hoc for this proposal, and well-characterized patient cohorts to identify, dissect and target dysregulated pathways that cause adaptive immune cell dysfunction during chronic hepatitis B. State-of-the-art static and dynamic imaging will be employed to analyze the behavior of adaptive immune cells that ultimately differentiate into dysfunctional cells in the liver at unprecedented levels of spatial and temporal resolution. In parallel, high-dimensional flow cytometry and single cell sequencing in mouse models of HBV pathogenesis and in chronically infected patients will reveal the underlying proteogenomic landscape and heterogeneity that cause adaptive immune cell dysfunction. Finally, immunoregulatory mechanisms already identified in preliminary work or that will emerge from the above analyses will be targeted both in vitro and in vivo. By studying all the main players of HBV immunity together with state-of-the-art techniques and by interconnecting research with mouse models with analyses of human samples, we are in a unique position to make fundamental leaps in our understanding of adaptive immunity and viral pathogenesis. We are confident that the results emerging from this proposal will have the potential to guide the design of novel, rational strategies to direct the immune system to terminate chronic HBV infection and its associated costs and complications.

Mots-clés : hepatitis b,liver,cd8 t cells,b cells,chronic viral infection,multiphoton intravital imaging,t cell dysfunction
Projet ERC : Neuroheart (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Université Johann Wolfgang Goethe de Francfort-sur-le-Main — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2486183.0 €

Aging is a major risk factor for impaired cardiovascular health. The aging myocardium is characterized by endothelial cell dysfunction, diastolic and systolic impairment, increased hypertrophy and fibrosis and electrophysiological alterations that predisposes the elderly to arrhythmic risk. The mechanism of age-associated pathophysiological alterations are incompletely understood. In preliminary data, we report that aging is associated with a decline in axon density in the heart. Since vessels align with nerves and this interplay is critical for tissue homeostasis in other organs, we postulate that an impairment of the neuro-vascular interface in the aging heart may contribute to age-associated pathologies. To address this hypothesis, we will first characterise axon extension and patterning of different nerve fibres in the heart. Second, we will decipher the underlying mechanisms mediating the reduction of axon density in the aging heart. Based on preliminary data documenting an induction of the repulsive Semaphorin 3a (SEMA3A) in endothelial cells of the aging heart, we will address if endothelial SEMA3a mediates the effect. Third, we will determine the consequences of reduced neuron density: We will i) study electrical stability and arrhythmias; ii) We will explore the nerve secretome aiming to identify paracrine signals that possibly control cardiac tissue homeostasis and age-associated alterations. iii) We will assess the cross-talk of neurons with age-associated cardiac inflammation. Finally, we will determine whether senescence may contribute to neuro-vascular alterations during aging. We will extend preliminary data suggesting that senolytics interfere with the age-induced decline in axon density. Together, these data will decipher the so far unexplored role of the neuro-vascular interaction in the aging heart. We believe that restoring or preserving a functional cross-talk between neurons and the vasculature may contribute to healthy cardiac aging.

Mots-clés : cardiac aging,endothelial dysfunction
Projet ERC : CHIP-AVS (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université Johann Wolfgang Goethe de Francfort-sur-le-Main — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2225906.0 €

Degenerative aortic valve stenosis is the most common acquire heart valve disease and will continue to increase as a result of an aging population. There is currently no medical therapy established to halt progression of aortic stenosis and the only definitive treatment is aortic valve replacement either by surgery or transcatheter aortic valve replacement (TAVR). Without valve replacement, the 2 year mortality rate approximates 50 % once patients are symptomatic. Although a number of general risk factors have been described for developing calcified aortic valve disease, risk prediction for progression of CAVD to severe stenosis is still poor. We demonstrated that somatic mutations associated with expansion of hematopoietic cells (“clonal haematopoiesis“ (CH)) are associated with a poor prognosis of patients with aortic valve stenosis undergoing TAVR. This application aims to address the following major points. We will determine 1) how mutations in the most prevalent CH-driver gene DNMT3A may directly or indirectly affect the pathophysiological processes leading to aortic valve stenosis, and 2) which type of mutation is particularly involved in mediating the poor prognosis. 3) We will determine the impact of CH on the reversibility of cardiac fibrosis after successful replacement of the aortic valve, and 4) determine the relation of CH with senescence and inflammaging. We will use cutting edge single cell and omics technologies to decipher the pathophysiological effects in patient tissues and circulating blood samples and will explore the pathomechanisms induced by DNMT3A CH-driver mutation by assessing cellular communication processes in vitro. The discovery of relevant of immune system mediated complexities in the progression of aortic valve stenosis and consequent cardiac fibrosis is expected to identify biomarkers and possible novel therapeutic targets to specifically intervene in patients with a high risk for worse outcome.
Projet ERC : WINSUN (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
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 : 2498750.0 €

The Sun provides the energy necessary to sustain life on Earth, making it a star of unique importance for human society. It is also the only star whose surface we can resolve to reveal the richness of the complex processes acting there, creating a highly dynamic and varied environment. Much of the structure and dynamics visible on the Sun is caused by the intricately structured magnetic field and its interaction with the turbulent plasma. However, there are considerable gaps in our knowledge of the fundamental physical processes driving the evolution of the solar magnetic field, from its generation to its removal from the solar surface, and how the field drives solar activity and variability. To fill these gaps, this project will make use of powerful new observational missions and facilities: Solar Orbiter, Sunrise III, Daniel K. Inouye Solar Telescope (DKIST) and Aditya-L1, which will open new windows onto the Sun and its magnetic field. They will provide the first clear views of the solar poles (Solar Orbiter), and the highest spatial resolution ever in the Extreme Ultraviolet (Solar Orbiter) and in the visible (DKIST). They will also explore a new spectral window onto the solar photosphere and chromosphere (Sunrise III, Aditya-L1). The advanced instrumentation, complemented by novel data analysis techniques and state-of-the-art magneto-hydrodynamic simulations, will allow tackling, often in entirely new ways, long-standing difficult problems that have resisted previous attempts at resolving them. Elucidating these will provide deep insights into the life cycle of the magnetic field, and how it affects the Sun’s atmosphere and variability. A decade’s efforts by me and my group has positioned us at the core of the new instrumentation, data analysis techniques and simulations, making us very well placed to apply the exciting data from the new resources to unravelling the fundamental physics driving the evolution of the Sun’s magnetic field.

Mots-clés : solar magnetic field,solar activity,solar variability,solar atmosphere
Projet ERC : EXPEDITE (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université de Naples - Frédéric-II — Pays : Italie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 156000.0 €

In vivo gene therapy based on a single administration of adeno-associated viral (AAV) vectors is emerging as an effective therapeutic option for both monogenic and complex diseases. Given the episomal nature of the AAV genome, its applications are limited to non-replicating tissues like retina or adult liver. Several AAV-based products that target these tissues are either approved or in advanced clinical development. Despite this, some limitations still remain, including: the potential for insertional mutagenesis associated with genome-wide AAV integration; the loss of transgene expression from replicating tissues like newborn liver; and the challenge to counteract toxic gain-of-function mutations, which cause dominant diseases for which canonical gene replacement is ineffective. EXPEDITE aims to integrate therapeutic DNA at desired genomic loci safely and effectively, thus overcoming the above limitations. EXPEDITE will go beyond the current state-of-the-art by implementing and comparing two parallel strategies: (i) novel Cas fusion proteins to recruit DNA repair machineries at induced double stand breaks (DSBs) to maximize on-target donor DNA integration; (ii) novel cleavage-free platforms for therapeutic DNA integration, based on transposases or bacterial single strand-DNA annealing proteins. The therapeutic relevance of these platforms will be tested in the retina and liver, two highly relevant tissues for gene therapy, using animal models of inherited retinal degenerations and lysosomal storage diseases, respectively, and, ultimately, non human primates. To reduce the risk of potential off-targets, EXPEDITE will also test non-viral vectors for transient delivery of the genome editing tools while delivering the donor DNA via AAV. The results from EXPEDITE will allow significant expansion of the patient population that can benefit from in vivo gene therapy and may represent a change of paradigm for gene therapy by replacing canonical gene addition approaches.

Mots-clés : gene therapy,adeno associated viral vectors,aav,genome editing,liver,retina
Projet ERC : GALPHYS (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe Sciences
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 : 1945250.0 €

Lookback studies have assembled a fairly complete census of galaxies over 85% of cosmic time and established that the bulk of stars, which today reside in massive ellipticals and spirals, formed rapidly at redshift z~1–3. Most of this star formation took place in massive gas-rich, turbulent disks, which already followed tight scaling relations in their global properties, and in which dense bulges, fast growing central black holes, and galactic winds were ubiquitous. The next frontier is to uncover the physical mechanisms inside galaxies that govern the buildup of stars and the emergence of galactic structure. This goal can only be reached by resolving gas motions and distributions on the Toomre scale of ~1 kpc at z>1, requiring ~25 times sharper views than typically achieved so far. Revolutionary improvements in observing sensitivity and resolution now make this possible: the advent in 2022 of the most advanced near-IR adaptive optics-assisted integral field spectrograph ERIS at the Very Large Telescope. GALPHYS centers on an ambitious 900-hour ERIS Guaranteed Time program led by the applicant, and exploits key synergies with cutting-edge (sub-)millimeter interferometry at IRAM/NOEMA and ALMA of which the applicant is a core member of Guaranteed and Open Time programs. The requested 3 postdoc and 2 PhD positions are required for the PI to establish a research group to execute the program. GALPHYS will produce breakthroughs in the most important, outstanding issues in galaxy evolution: (1) mass and angular momentum transport, (2) the origin of gas turbulence, (3) the evolution of giant star-forming complexes, and (4) the physics of outflows powered by stellar and AGN feedback. GALPHYS will provide excellent training for junior scientists and an unmatched benchmark of lasting legacy in galaxy evolution.

Mots-clés : galaxy evolution,galaxy kinematics,galaxy structure,high redshift galaxies
Projet ERC : ULEEM (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
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 : 2488216.0 €

This proposal aims at the development and application of Ultrafast Low-Energy Electron Microscopy (ULEEM), a new experimental technique for studying dynamics at surfaces. It addresses a key question in ultrafast surface science, namely the observation of rapid structural changes with high spatial and temporal resolution, and with ultimate surface sensitivity down to the monolayer level. In order to achieve this goal, a number of conceptual and technological challenges will need to be addressed. This project is designed to support a comprehensive approach to the successful implementation of ULEEM. Pulsed electron source concepts and electron pulse compression schemes will be realized for the conditions of low-energy electron microscopy. Furthermore, tailored contrast mechanisms will be employed to enhance the time-resolved mapping of specific structural features and domains. With this newly established methodology, we will study a selected set of model systems and nonequilibrium phenomena to explore ultrafast surface imaging of the dynamics and control of phase transformations, interlayer energy transfer in van der Waals heterostructures, and the excitation and propagation of collective modes.

Mots-clés : ultrafast dynamics at surfaces,2d heterostructures,ultrafast electron microscopy and diffraction,metastable states,ultrafast phase transitions