Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MELCART (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Institut Pasteur — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 1886217.5 €

As living beings move, touch, or grow, the tissues within them are subject to mechanical stresses that act over minutes, hours, or days. These efforts play a critical role at all stages of life, from early embryonic development to homeostasis in adult tissues or disease progression. Mechanobiology has emerged in response to this realization and has led to many discoveries on mechanosensitive pathways in individual cells. However we are still very far from relating the single-cell behavior to the response within a real tissue that contains mixtures of cell types which are organized in complex 3D structures. In this project we will expand mechanobiology to 3D tissues by developing a new class of micro-devices, based on soft robotics and metamaterials, for active mechanical forcing of spheroids and organoids. We will couple this active forcing with multiscale cytometry methods that we have pioneered, in addition to concepts from many-body soft matter physics. This will allow us to understand how the rheological responses of individual cells add up to result in the global tissue rheology. The outcome is a new paradigm to probe phenotypic changes, e.g. the epithelial-mesenchymal transition in a cancer model or the cellular differentiation and 3D organization in a maturing organoid. Conversely we will map how global mechanical stresses are transferred to individual cells that in turn respond to the forces locally. This will allow us to engineer dynamical forcing strategies to guide the biological response of specific populations within a complex co-culture. When applied to developing organoids this will lead to strategies to mature individual cell types, in view of using them for cell therapy. In the case of cancer models we will identify mechanosensitive pathways that can be targeted by drugs to treat real tumors. By working on the joint cutting edge of technology, physics, and biology, we will manipulate in vitro models with real impact on human health.

Mots-clés : microfluidics,organoids,cancer,mechanobiology
Projet ERC : Oecologie (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Texts and Concepts
Entité participante : Université Sorbonne Nouvelle — Pays : France — Rôle : PI
Acronyme de l'entité : Sorbonne Nouvelle
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1366099.0 €

Originally, ‘ecology’ was more than just the name of a biological subdiscipline. When its inventor, the German biologist Ernst Haeckel, first coined the term (German: ‘Oecologie’) in his 1866 work General Morphology, he was in fact shaping the contours of a larger philosophical project rooted in German anthropology and aesthetics. The aim of this ERC research project is to uncover this forgotten enterprise and to assess its implications. To do so, it proposes a radical change of perspective, broadening the view from the scientific dimension emphasized by Haeckel’s successors to its philosophical sources. By analyzing Haeckel’s original interpretation of the metaphor of oikos (‘habitat’, ‘dwelling’) and oikeiosis (‘adaptation’, ‘appropriation’), the project traces the shift in emphasis from the viewpoint of an external and distant God to the living organism’s own capacities for adaptation and domestic ‘householding’; it examines the place of the human organism in this ecology, as a natural being, as a human housekeeper, as part of a larger household, and as an aesthetic spectator, representing and visualizing the world from within and from the terrestrial habitat. Using a transversal methodology situated at the intersection of conceptual history, history of philosophy, history of science, aesthetics and philology, Oecologie explores the context of the emergence of this first strand of ecological thought in nineteenth-century European evolutionism (1), its philosophical sources and its debt to earlier thinkers in the German tradition, such as Kant, Alexander von Humboldt and Goethe (2), its ambiguous history of reception both in Germany and abroad (3). Last but not least, it examines the actuality and relevance of such an ecology for environmental studies and the contemporary sciences, which are struggling to regain their lost unity, to refocus on the human being, and to bridge the gap between the scientific and political strands of ecology (4).

Mots-clés : ecology,philosophy of ecology,history of ecology,haeckel,german aesthetics,arts and science,philosophical anthropology,early modern cosmology,geographical thought,evolutionary theory,darwinism,oikos,habitat,economy of nature,adaptation,balance of nature,biodiversity,non epistemic values in science,aesthetic feeling,kant,alexander von humboldt,goethe,lamarck,german history of ideas,environmental studies,eco criticism
Projet ERC : NANOCLICS (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Institut national de recherche pour l'agriculture, l'alimentation et l'environnement — Pays : France — Rôle : PI
Acronyme de l'entité : Inrae
Type d'entité : Recherche
Financement ERC de l'entité : 2499875.0 €

The NANOCLICS project will demonstrate that metallic polymers of just a few atoms linked to organic molecules are the pivotal organomineral association structures in soils. They form an hydrated gel nanostructure called nanoCLICs. The project will: 1) explore their structure at the nanoscale in 10 soil types; 2) elucidate the nanoCLICs dynamics; and 3) quantify their contribution to soil carbon sequestration. The project will rely on the nanoCLICs molecular model that I previously developed. Organomineral associations stabilize organic compounds in soils, which is crucial for long-term carbon sequestration and plant nutrition. Demonstrating that metallic polymers of a few atoms linked to organic molecules are the molecular units of these associations is key to understanding carbon stabilization, but their nanostructure and dynamics must first be deciphered. Organic molecule adsorption on mineral surfaces is often put forward to explain the persistence of organic compounds in soils. However, direct in situ characterization in intact samples has been challenging due to the lack of true nanometer-scale resolution analyses. My recent studies have demonstrated that organomineral nanostructures can now be characterized using advanced nanometer-resolved nanoscience techniques. By using these techniques, which I recently applied to Andosols, we will fulfil three objectives: STRUCTURE: we will explore the nanoCLIs structure at the nanoscale in 10 soil types using nanoscale spatially resolved imaging techniques DYNAMICS: we will elucidate the nanoCLICs dynamics (formation, evolution, disruption) using a specifically developed long-term column experiment MODEL: we will quantify nanoCLICs contributions to soil carbon sequestration by linking nanoscale organomineral knowledge with operational carbon storage models The NANOCLICS project will unlock crucial insights into the stabilization and destabilization of soil organic matter, enhancing soil carbon management.

Mots-clés : soil organomineral associations,carbone storage,nanoscale,soil carbon dynamics
Projet ERC : circRNA4DMD (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

RNA therapeutics is an emerging field explored in various types of diseases such as genetic disorders, cancer, inflammation and viral infections. Currently, most of the research focuses on the delivery of mRNA molecules that will transiently express a desired protein that can replace a defective protein or manipulate gene expression in the cells. My lab was the first to show systemic, cell-specific delivery of mRNA molecules in animals. Our approach and our novel amino lipids were translated to several clinical trials in the field of infectious and monogenic diseases. In protein replacement therapy, the main hurdle of using mRNA is the relative short half life of the mRNA. To address this, I suggest an approach for long-term expression: Circular RNA (circRNA), a covalently closed loop single stranded RNA that has a significant prolonged stability compared to linear mRNA. Thus, presents an immense advantage in protein replacement therapy. Duchenne muscular dystrophy (DMD) is caused by X-linked recessive mutation in dystrophin gene, leading to lack of functional dystrophin protein. This disease affects 1:5,000 males, causes a progressive loss of muscle tissues, ultimately leading to disability and premature death. Because DMD pathology is caused by the lack of functional dystrophin, restoring the function of dystrophin is a potential therapeutic strategy. As Lipid nanoparticles (LNPs) are the most clinically advanced candidate for RNA delivery, able to entrap large RNA payloads, herein I propose an innovative multidisciplinary approach for the specific delivery of circRNA-LNPs to muscle cells that will express the dystrophin protein and replace the defective one in a DMD mouse model. The long-term expression of the circRNA will offer new hope for the treatment of monogenetic diseases such as DMD. This approach may ultimately become a novel therapeutic modality for DMD and open new avenues for implementing circRNAs for other types of genetic disorders and vaccines

Mots-clés : lipid nanoparticles ionizible lipids rna therapeutics mrna circular rna duchenne muscular dystrophy
Projet ERC : MystIMEC (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 3498426.0 €

Compared to my previous Advanced ERC grants, this proposal is fundamentally different not only concerning its topic but also regarding its ambition to offer greater societal impact by coupling knowledge gain tighter to translation. It promises to obtain new insights in an understudied endothelial cell (EC) subtype with immunomodulatory gene signatures (coined “IMECs”), highly relevant for alternative immunotherapy development. Indeed, silencing immunosuppressive genes in IMECs offers unprece-dented opportunities to improve the efficacy of and to overcome the resistance to current anti-cancer immunotherapy, to which the immunosuppressive tumor endothelium contributes. To identify previously unknown/unmined (“virgin”) drug targets, we also focus on “mystery” genes, lacking func-tional annotation / PubMed reports (comprising 30% of the human coding genome). We developed: (i) an innovative artificial intelligence (AI)-based tool (SCMYSTERYDENTIFIER) to predict new immunosuppres-sive functions for endothelial “mystery” genes; and (ii) a revolutionizing (“REVOLT”) technology (based on injecting EC-selective lipid nanoparticles containing sgRNA in mice expressing Cas9 selectively in ECs) to generate EC-specific knockout mice rapidly (days)/inexpensively (300€/mouse) at an unprece-dented scale in order to validate these targets. Demystifying the mystery genome offers formidable opportunities for knowledge gain and therapy development. We will validate 50 new EC targets and aspire to identify and patent 5 previously unknown targets for alternative IMEC-based immunotherapy. The SCMYSTERYDENTIFIER tool can be made generic to discover any type of function for mystery genes in any cell type, while the REVOLT technology promises to revolutionize the pace of genetic research in the vascular biology field, offering formidable impact for the research community in academia and pharma.

Mots-clés : endothelial cells,immunotherapy,single cell omics,gene editing,target discovery,target validation
Projet ERC : KolmoCrypt (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université de Tel Aviv — Pays : Israël — Rôle : Partner
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 311500.0 €

Cryptography—and its basic tasks such as encryption, authentication and key exchange—is essential for ensuring privacy and security on the Internet. The question of whether “unbreakable” encryption methods exist has fascinated mathematicians and cryptographers for thousands of years, and is closely related to the famous NP vs. P problem. This question is still wide open and consequently, Internet security today relies on cryptographic constructions based on the *conjectured* hardness of some computational problems (such as e.g., the factoring problem, the discrete logarithms problem or various noisy linear algebra problems). However, these conjectured hard problems all contain significant (e.g., algebraic) *structure*, that may make them vulnerable to attacks. Furthermore, for tasks such as key exchange and public-key encryption, only a *handful* of candidate hard problems are known on which these tasks can be based. As a result, some unexpected algorithmic developments for structured problems could upend the whole infrastructure we rely on for communicating and transacting on the Internet.  In this project, we propose to develop an alternative approach: a foundation for provably-secure Cryptography from *unstructured hardness* assumptions. Towards resolving this long-standing challenge, we will leverage our recently-discovered connection between Cryptography and the seemingly unrelated area of Kolmogorov Complexity. Specifically, we will develop new hardness assumptions rooted in Kolmogorov Complexity on which the cryptographic tasks (e.g., private-key encryption, key-exchange, public-key encryption) can be based. Critically, these assumptions will lack algebraic and other computational structure that may make them vulnerable to attacks. Overall, KolmoCrypt will provide a new theoretical foundation for the hardness assumptions on which Cryptography is based, and ultimately, a more secure foundation for the Internet (and beyond).

Mots-clés : cryptography,foundations of cryptography,computational hardness,kolmogorov complexity,provable security,computational hardness assumptions,one way functions
Projet ERC : XenoAD (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Understanding therapeutic opportunities in Alzheimer’s disease (AD), the most common form of progressive neurodegeneration, is limited due to lack of animal models that replicate the disease’s consecutive stages. We achieved a breakthrough by xenografting human stem cell-derived neurons into mouse brains, where they integrate and survive up to two years, developing typical AD hallmarks. Neighbouring mouse neurons remain resilient to AD, underscoring unique human neuronal features not mirrored in rodents. Significant challenges persist, particularly modelling aging, the primary and most elusive risk factor for sporadic AD. The current model also lacks human microglia, crucial carriers of genetic risk for AD. We need to measure the impact of progressive disease on neuron function, as maintaining brain function is the ultimate goal. To address these challenges, we propose a novel method of transplanting human neurons that preserve their epigenetic markers of aging, together with human microglia in double xenografts. Concurrently, we will investigate neurons from healthy aging centenarians to understand the basis of AD resilience at old age. Our research tackles critical questions: (1) How do age-associated epigenetic changes modulate disease phenotype? (2) What is the molecular basis of resilience in centenarians? (3) Do newly discovered drug targets benefit neuronal function? (4) Which blood biomarkers track the effect of experimental treatments? This study focuses on human biology, using human cells, genes, and proteins, ensuring rapid translation to clinical settings. By the project’s end, we expect to identify at least four novel drug targets and their biomarkers, validated through preclinical studies. Developing the first animal models for sporadic AD is transformative for the field, allowing to map the molecular pathways in human neurons from health to degeneration. The work will lead to new therapeutics but may also lead to cell transplantation therapies for AD.

Mots-clés : alzheimer s disease,xenografts,aging,models
Projet ERC : OptiMEG (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2296090.0 €

Epilepsy presurgical evaluation consists in mapping the brain regions generating pathological activities, which can be surgically resected. The current method of choice is stereotaxic electroencephalography (SEEG), an invasive procedure which involves implanting a limited number of electrodes in the brain. Thanks to 4-He Optically Pumped Magnetometers (OPMs), a new generation of mobile sensors, I will be able to record magnetic activity non-invasively across the whole brain. Compared to classical magnetoencephalography, OPMs can be placed directly on the scalp, drastically reducing the distance to the brain and opening the way to optimise spatial sampling of magnetic fields. Thus, the OptiMEG project aims to develop a personalized, non-invasive tool based on OPMs for localizing epileptic activity. I will use intracerebral (SEEG) signals recorded simultaneously with OPMs in order to learn how to retrieve the deep signals measured in SEEG from OPM. My expertise in MEG and the collaboration I have already established with clinicians at the Timone Hospital will guarantee the success of OptiMEG.  The questions that I will address are: 1) Design the optimal placement of mobile OPM sensors for retrieving non-invasively activity from deep brain regions 2) Identify the signatures on the surface OPM signals of the different regions seen on the deep SEEG contacts 3) Validate the resulting signatures as biomarkers in a clinical setting  The OptiMEG project will revolutionize clinical practice by retrieving activity from deep brain regions without requiring implantation of depth electrodes, with unprecedented spatial and temporal resolution. It will produce a more precise diagnostic by capturing activity across the whole brain. allow more patients to have access to epilepsy surgery, lowering risks and costs compared to SEEG. It will also bring non-invasive access to deep brain regions in other neurological pathologies and in fundamental neuroscience.

Mots-clés : epilepsy,magnetoencephalography,optically pumped magnetometers,intracerebral eeg
Projet ERC : DIPAMUTA (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
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 : 723373.75 €

Digitalization is revolutionizing our economies. The volume of digital payments has increased exponentially, fueled by electronic commerce and financial transactions. Giant internet platforms are now dominant players at the global level and manage to avoid most taxes. New payment service providers are undermining the traditional business model of banks. We lack a conceptual framework for guiding the regulatory and taxation reforms that are needed to adapt to this digital revolution. I will contribute to provide such a framework by examining 3 questions: 1. Digital payments: regulation and/or public provision? I will study how the banking regulatory model, focused essentially on prudential and monetary issues, needs to be adapted to take care of antitrust and privacy issues. I will also examine if the public provision of digital payments can eliminate the risk of domination of the payments industry by a few private platforms. 2. Should we tax digital payments? Current taxes on digital services and financial transactions are, by and large, evaded by businesses. An alternative is to introduce a (small) tax on all digital payments. It could generate a sizable revenue, would be easy to implement, difficult to avoid, but would also generate distortions. I will incorporate payments into a general equilibrium model, and carry out a cost benefit analysis of this “tax for the 21st century”. 3. Multidimensional taxation in a digitalized economy Traditional sectors are deeply impacted by the digitalization of the economy. Thus, it would be appropriate to consider a global reform of the tax system. However, an important theoretical hurdle is to find a way to solve general screening problems with multiple instruments and multiple dimensions of heterogeneity, which nobody has done so far. Based on a recent breakthrough in numerical methods, I will provide such a general solution, and apply it to multidimensional taxation in a digitalized economy.

Mots-clés : multidimensional screening,taxation,payments economics,digital currencies,platform competition