Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ASTEC (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed Matter Physics
Entité participante : Sorbonne Université — Pays : France — Rôle : PI
Acronyme de l'entité : Sorbonne U
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2270937.5 €

In three dimensional systems, elementary particles are divided exclusively between fermions (which exclude each others) and bosons (which bunch together) according to the phase acquired by the wavefunction when two particles are exchanged. The situation is different in two-dimensional systems which can host new particles called anyons, for which the exchange phase can take any value, and which obey partial exclusion, between fermions and bosons. Interestingly, these quasiparticles keep a memory of the exchanges between them that is protected from local perturbations of their trajectories: one speaks of topological protection. This protection is at the heart of the interest for anyons, as specific types of anyons called non-abelian are the building blocks of topological quantum computing that would be protected from decoherence. The existence of these quasiparticles was predicted forty years ago in two-dimensional conductors in the fractional quantum Hall regime. However, despite intense experimental and theoretical efforts, direct signatures of their fractional statistics have only been observed recently, offering only now the possibility to characterize fractional statistics and to exploit it for new functionalities.  The purpose of this project is to quantitatively investigate the statistics of anyons by probing their tendency to bunch together or exclude each others in a nanoscale collider. The different phases of the fractional quantum Hall effect offer a very vast and almost completely unexplored variety of anyons. I will characterize the differences between different statistics, including the most interesting non-abelian case. I will also investigate the robustness of the signatures of fractional statistics and to which extent they can be considered as topologically protected. Finally, I will probe anyon statistics in the time-domain regime, where anyon emission is dynamically controlled, which is a necessary condition for quantum information perspectives.

Mots-clés : quantum noise,anyons,collider,two particle interferences,time dependent transport
Projet ERC : RIPECROP (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Université de Navarre — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2411500.0 €

Cancer immunotherapy achieves unprecedented efficacy against a number of malignant diseases. Preclinical experiments in mouse models conclude that type-1 dendritic cells (cDC1) that present tumor antigens are an absolute requirement for most immunotherapy strategies to be efficacious, including those routinely applied to cancer patients at present. cDC1 cells are specialized in redirecting engulfed cell-associated antigens to the class I MHC antigen-presentation pathway in the context of IL-12 production and co-stimulation, at least when cDC1 cells are in the presence of moieties denoting viral infection. Such phenomena are key to prime anti-tumor T lymphocytes through a mechanism known as crosspriming. The RIPECROP project will test immunotherapy agents that enhance the numbers and performance of cDC1 in the tumor tissue microenvironment. The strategies will be based on mRNA constructs that will encode engineered forms of the cDC1 growth factor sFLT-3L, single-chain interleukin-12, cDC1 specific chemoattractants and bispecific costimulatory ligands targeted to surface proteins of cDC1 cells. The new therapeutic agents in the form of coding mRNAs will be expressed in vivo either intratumorally or using the mRNA-transferred liver as an internal “biofactory” to systemically produce the encoded proteins and their combinations. Innovative in-vivo screenings based on hydrodynamic gene transfer of the liver with various expression plasmids encoding heterodimerization systems will be performed to identify suitable new mRNA-based immunotherapeutic chimeric constructs to enhance antitumor T-cell crosspriming. Overall, a novel mRNA-based toolbox will be studied both in terms of anti-tumor efficacy and regarding the mechanisms of action, in such a manner, that crosspriming will become exploitable in combinatorial approaches for cancer immunotherapy.

Mots-clés : crosspriming,cancer immunotherapy,mrna,intratumoral,adoptive t cell therapy,viral mimetics,radiotherapy,synergistic immunotherapy combinations
Projet ERC : APATE (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth System Science
Entité participante : Université d'Orléans — Pays : France — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2784505.0 €

The existence of an atmosphere enriched in H and He around the Earth as it formed has often been proposed. One hypothesis suggests that it could have been captured from the gas present in the proto-planetary disk, before its evaporation. Subsequently, a secondary atmosphere would have been degassed or brought in by a late veneer of chondritic/cometary material. Although this model is regularly evoked using giant planets for comparison, there is no geological proof for its existence, except possibly for the neon in the Earth's mantle. While the model has a flaw (mainly relating to chronology, as the gas from the disk is lost in <6 My while the Earth formed over a period of more than 30My), the solar-type neon in the Earth's mantle is an argument for the existence of such a captured atmosphere, which partially dissolved into a magma ocean. A second scenario for a primordial H2/He-rich atmosphere is the degassing of a mantle that contained implanted solar wind. The APATE project aims to study the isotopic composition of neon in the Earth's mantle in order to determine if this composition is the same as that of the nebula or the solar wind material. I will investigate the degassing processes of magmas experimentally and numerically in order to study the isotopic fractionation that occurs during bubble formation and to determine whether the measured neon isotopic composition can provide an accurate composition for the original mantle. The project aims to calculate the amount of neon that can be incorporated into a magma ocean by establishing the atmospheric pressure of the captured atmosphere and by studying the dynamics of the magma ocean. I will also explore the hypothesis involving solar wind irradiation. Using simulations of irradiation, I will identify those conditions under which this model is realistic and its implications for the Earth’s (isotopic/chemical) composition. The origin of light solar volatiles will then be explored by the APATE project.

Mots-clés : origin of volatiles on earth magma ocean solar wind irradiation
Projet ERC : MONOSPLIT (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and I mmunotherapy
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499990.0 €

Macrophages are key players in organ development, tissue maintenance, and the immune defense of vertebrate organisms. These cells are initially established during embryonic development, but most tissue-resident macrophage compartments are progressively seeded and often even replaced by monocyte-derived cells. Monocytes and their macrophage progeny critically contribute to a wide range of pathologies, including autoinflammatory, cardiovascular, and metabolic disorders, as well as cancer. Given their central role in physiology and pathophysiology, these cells are attractive targets for therapeutic intervention. This will, however, require an in-depth understanding of monocyte-to-macrophage trajectories, whose comprehensive study in mice and man is the goal of this proposal. Beyond these translational implications, our studies are particularly well-timed, given new exciting findings: thus, monocytes were recently shown to arise from distinct developmental trajectories, and we discovered that this developmental monocyte dichotomy translates into tissue macrophage heterogeneity with probable significant functional impact. Here, we propose to follow up on our recent intriguing finding and use murine fate mapping and novel Csf1r-targeted genetic perturbations, combined with a high-resolution single-cell-based imaging and omics analysis of murine and human blood, to explore the impact of developmental monocyte dichotomy on health and disease in man and mice. An in-depth understanding of the two monocyte trajectories, their differential dominance following infections, and differential fates in distinct tissues will have significant value for the future development of strategies for tissue macrophage manipulation. Moreover, our detailed analysis of human blood might incentivize routine monitoring of the monocyte-to-macrophage axis for diagnosis.

Mots-clés : monocytes,macrophages,bacterial and viral infections,hematopoiesis,lineage tracing,degron based perturbation,lung,intestines,blood
Projet ERC : Cells2Tissues (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative B iology : from Genes and Genomes to S ystems
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2937179.0 €

One of the most fundamental challenges in contemporary biology is in fact also one of the most classical ones: how to comprehend macroscopic tissue function from the activities of its microscopic cellular components. The remarkable advent of single cell genomics over the last decade is realizing this challenge at unprecedented scales. Measurements of the molecular states of thousands or even millions of cells can now be acquired efficiently, and tools for describing cellular states phenomenologically became well established. But how to model ensemble of cells in tissues is paradoxically even more difficult than before given this new unprecedented experimental resolution. To this end we will develop a new computational and theoretical framework for understanding ensembles of single cells as they interact and dynamically differentiate, proliferate or degrade. Parametric and mechanistic models for defining microscopic cell states over a mathematical manifold will be developed, and the dynamics of ensembles of cells over time and in space will be inferred from new experimental approaches capturing whole tissues over time or within spatially registered domains. Importantly, our models will describe tissues dynamics as change in specific gene regulatory, epigenomic and signaling programs, and we will develop high throughput experiments to combinatorically perturb embryonic and hematopoietic systems in order to test such models extensively. Our research will thereby extend single cell-centric models toward describing dynamics in tissues, with experiments and data collection aiming at rapid translation of the models to actionable and testable strategies for manipulating systems of interest. This will be applied to transparent and epigenetically precise cell type engineering, to discoveries using a unique resource on human hematopoietic ageing and to deep tissue level analysis of combination immunotherapy.

Mots-clés : single cell genomics,transcriptional manifolds,epigenetics of embryonic development,blood ageing
Projet ERC : CryoSTEM (Horizon Europe, appel 2021, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and Analytical Chemical Sciences
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499987.0 €

Cryo-electron microscopy has revolutionized the field of structural biology, primarily for macromolecular structure but also for cells and tissue sections—achieving resolutions at the limit of physical optics. While wide-field transmission EM (TEM) with phase contrast by defocus is the most commonly used modality in biology, the alternative, scanning transmission EM (STEM), has emerged as the mode of choice for atomic resolution in materials science. Seeking to endow biology with the benefits of STEM, our lab established STEM for cryo-tomography of biological cells and demonstrated its advantages for thick specimens and compositional contrast. We now seek to extend cryo-STEM to high-resolution, with an emphasis on tomography, by means of coherent detection (Obj1). This will be achieved by the method of integrated differential phase contrast (iDPC) using a segmented detector, from which we obtain simultaneously phase and depth contrast in a single scan. The major expected benefits are: 1) minimization of image aberration, especially defocus with its associated complications for image interpretation, 2) reduction of beam-induced radiation damage by means of flexible scan and sampling patterns, and 3) improved reconstruction for tomography based on tailored data acquisition. We will validate the new methods for single particle analysis on standard macromolecular substrates and compare them to current state-of-the-art methods. Further, we will apply the new developments in 3D imaging to explore novel large-scale structures in chromatin we observed recently by whole-cell cryo-STEM tomography using current, low-resolution methods (Obj2). Labelling with halogenated nucleotides will reveal sites of active transcription or DNA synthesis. The proposed approaches’ expected broad applicability and STEM’s unrealized potential for hardware simplicity should together ensure the wide adoption of cryo-STEM methods in biology, accelerated by our dissemination efforts (Obj3).

Mots-clés : electron microscopy,tomography,scanning transmission em,cryo em,chromatin
Projet ERC : BoX-BOOM (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Materials Engineering
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2473806.0 €

Man-made organic optics relies almost exclusively on amorphous polymers. These cheap, readily processable and highly versatile materials, however, offer a relatively low refractive index, dramatically limiting their ability to generate the high-index contrast necessary for producing scattering layers, photonic crystals and efficient dielectric reflectors. We here propose to establish a new class of novel organic crystalline optical materials and devices by drawing inspiration from the highly birefringent high-index organic molecular crystals nature has to offer, such as those found in dielectric reflectors, photonic crystals and photonic glasses that take part in structural coloration and vision. The crystal structure of these materials, is based on a planar arrangement of hydrogen bonded molecules, which are weakly bound by van-der Waals bonds and weaker hydrogen bonding. The BoX-BOOM project aims to identify new cheap, functional and environmentally benign organic crystalline optical materials inspired by this structural motif, exhibited in biological systems, and to develop ways to grow them in a controllable manner as thin films using surface guided growth. The grown material will in turn be used in new types of optical elements and devices for a broad range of applications such as flat polarization optics, transparent dielectric metamaterials and birefringent volume holograms, all exploiting the high index and extreme birefringence of these materials. Work performed within the BoX-BOOM project will also shed light on the relationship between crystal structure and optical properties of this family of materials, setting the stage for identification of new high-index organic crystalline compounds and a range of applications taking advantage of this new thin-film optical technology.

Mots-clés : organic crystals birefringence biomimetic optics polarization optics
Projet ERC : ResistSOS (Horizon Europe, appel 2022, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention,  Diagnosis and T reatment of Human Diseases
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Background: A large fraction of cancer patients die because their tumors initially respond to drugs but later they evolve tolerance. Thus, resistance to diverse drugs, along with the soaring costs of new treatments, are emerging as major societal issues of the 2020s. Herein, we explore one of the most distressful examples, tolerance of lung cancer to EGFR-specific tyrosine kinase inhibitors (TKIs). Working hypothesis: In similarity to bacteria exposed to antibiotics, when cancer cells are exposed to TKIs they enlist SOS responses, which activate endogenous mutators. Hence, we will combine the relatively effective but mutagenic TKIs with drugs that disarm the mutators. This scheme will be applied on models of EGFR+ lung cancer, a disease that repeatedly evolves mutations and resistance, but eventually leaves millions of patients with no treatment choices. Specific aims: Our initial studies identified one triad of the SOS system: a sensor of cell death - GAS6, a mediator - AXL, GAS6’ receptor, and a mutator - low-fidelity DNA polymerases. Remarkably, blocking AXL using an antibody irreversibly prevented relapses when combined with EGFR inhibitors. Along with establishing this triad, we will employ transcriptomics, protetomics and metabolomics to resolve parallel mutators and sensors. Likewise, we will explore alternative ways to block resistance, for example by directly targeting DNA polymerases, MYC and purine metabolism. Aiming at strategies that minimize SOS enlisting, we will explore the premise of boosting immune destruction of cancer cells. Significance: According to the current status quo, next-generation inhibitors are being applied when resistance emerges. However, this scheme does not cure, only buys time. ResistSOS offers an alternative that might eradicate resistance and cure disease models following treatments that are based on deep understanding and blocking the mutagenic SOS response.

Mots-clés : lung cancer kinase inhibitors resistance to drugs mutations monoclonal antibodies cancer therapy resistance to antibiotics sos response
Projet ERC : MindReading (Horizon Europe, appel 2023, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499333.0 €

Can we decode the training data of a Deep Neural Network (DNN) directly from its parameters? Training data of DNNs are assumed safe. Recent findings by us and by others indicate that this is not the case, with severe implications on Data-Privacy. Yet, such findings shed light on why DNNs perform so well. On a different front: Can we decode what a person saw/heard/thinks directly from their brain activity? This may have huge benefits: communicate with “locked-in” patients, explore dreams, man-machine interfaces, enhance our understanding of the human brain. No risk of violating human privacy here, as thoughts do not “float” in the air and person’s collaboration is required. Each of those 2 questions is intriguing on its own, with far-reaching implications. Despite the inherent differences between Human Brains & DNNs, they also have much in common. Exploring the two in-tandem can lead to significant breakthroughs in both fields. Recent advancements in both areas, with recent incorporation of Deep-Learning (DL) tools to analyze brain activity, opens the door to explore the two jointly. Our expertise in both domains will enable explicit Encoding/Decoding between Brain activity & DNN activations, allowing to directly learn/infer from one about the other. Initial explorations indicate that our proposed goals, although ambitious, are within reach. Our intermediate goals in each domain are worthwhile on their own, forming a strong safety net. Expected outcomes include: •Deep Data-Privacy •Insights on DNNs, their Generalization & Vulnerabilities •Insights on of “what is encoded where” in the brain •New scientific tools for brain-scientists to explore the brain •Allow “locked-in” (ALS) patients to communicate their thoughts/needs •Use Brain scanning to improve DNNs & DNNs to improve Brain scanning Our project requires no human subjects nor BrainScience expertise; only publicly available datasets. All methods lie in Computer-Vision & DL, with impact on both DL & BrainScience.

Mots-clés : computer vision,deep learning,data reconstruction from brain activity,data reconstruction from deep networks,self supervised learning
Projet ERC : NEURO_OUTDOORS (Horizon Europe, appel 2024, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut Weizmann — Pays : Israël — Rôle : PI
Acronyme de l'entité : WIS
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3124999.0 €

Navigation is a key behavior, studied by multiple research fields. In ethology, wild animals are tracked outdoors using GPS tags as they navigate hundreds of meters or kilometers. In neuroscience, experiments are very different: laboratory animals are tracked inside small ~1×1-meter boxes, while recording the activity of navigation-related neurons – such as place cells, grid cells, head-direction cells, and border cells. However, it is unknown whether these spatial neurons, as studied in small laboratory-sized environments over 50 years, are relevant to large-scale navigation in the real world – outdoors.  In this proposal we will address this major gap, by conducting the first ever neural recordings from the brain’s “navigation circuit” in animals navigating outdoors. We will implant bats with tetrode microdrives, and will release them to fly on a remote, uninhabited oceanic island. Using custom wireless neural-logger and GPS, we will study the neurobiology of navigation – for the first time – in the real world.  We will explore: (1) How place cells and grid cells represent large natural habitats outdoors? (2) How these neurons encode 3D space – and in particular, altitude – in an open environment without a ceiling? (3) Are there border cells in animals navigating outdoors – e.g. border cells encoding the land/sea border, which is the “end of the world” for the bat? (4) Do head-direction cells represent a geographical compass? Specifically: do they maintain their head-direction tuning across all geographical locations on the island, and irrespective of moon movements? Preliminary experiments that we conducted on Latham Island, Tanzania, showed the feasibility of this project. We will record the same neurons outdoors and indoors, in a flight-tent on the island. This research will revolutionize the neurobiology of navigation – and it will be the first neurophysiological study, in any mammalian species and any brain region, of Neuroscience in the real world.

Mots-clés : place cells,head direction cells,grid cells,border cells,boundary cells,hippocampus,hippocampal formation,entorhinal cortex,neurophysiology,spatial cognition,navigation,bats