Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : NeuralSyntax (Horizon Europe, appel 2024, Consolidator 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 : 2000000.0 €

Our motor sequences obey syntax rules. From tying shoes to giving a speech, choosing the next action requires our brain to remember past actions, bridge across many seconds, and apply rules that create hierarchical syntax. Whereas past studies revealed how primary motor cortex drives actions, we poorly understand the transition mechanisms by which the brain strings actions into hierarchical variable sequences. The key obstacle is identifying deep hierarchical syntax rules in behavior and in neural sequences. This obstacle is met by studying birdsong that naturally segments to sequences of syllables. In the zebra finch, juveniles learn once from a tutor and fix a single sequence driven by a robust song-locked activity. Here, to study hierarchical syntax rules I will use canaries: virtuosos that learn and adapt such rules along and across seasons. Canaries produce a huge repertoire of songs that enable separate analysis of neural states and syllable acoustics when studying their rich and dynamic syntax rules. My previous work in canaries identified hidden neural states that keep a memory of sung syllables over several seconds and predict upcoming transitions. Here, I leverage this model to dissect transition mechanisms and elucidate: 1) neural activity in the premotor nucleus HVC that underlies flexible transitions between syllables; 2) integration of auditory and thalamic inputs for applying hierarchical syntax rules to select the next syllable; 3) neural state dynamics when adapting syntax rules for new songs; and 4) seasonal remodeling of HVC via neurogenesis. We use imaging, electrophysiology, and neural network simulations that integrate data across behavior, neural activity, and circuit levels of analysis. Our work will map the process by which basal ganglia and thalamocortical circuits generate and adapt hierarchical syntax rules over time, sensory, and social contexts, and might offer insights to dysfunction of motor sequence control in maladaptive conditions.

Mots-clés : electrophysiology songbird neuroscience neural network simulation syntax learning and generation motor sequences
Projet ERC : UDEMC (Horizon Europe, appel 2024, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 2000000.0 €

As humans age, Hematopoietic Stem and Progenitor Cells (HSPCs) accumulate preleukemic mutations (pLMs), forming preleukemic HSPCs (preL-HSPCs) and leading to clonal hematopoiesis (CH). While the link between CH and myeloid malignancies is established, predicting progression remains elusive. The Shlush lab aims to enhance myeloid malignancies outcomes through early diagnosis and treatment. Still, it faces three gaps: 1) lacking advanced tools for diagnosis/risk stratification beyond mutations, 2) insufficient understanding of pLMs functional consequences, and 3) absence of targeted therapies against pLMs. To address these challenges, our proposed specific aims are as follows: Aim 1: Develop a novel diagnostic tool for myeloid leukemia using single-cell RNA sequencing (scRNAseq) of peripheral blood HSPCs from 1300 patients and replace bone marrow (BM) analysis in the future. Such a cohort will allow the discovery of novel mechanisms in leukemia and improved diagnostics. Aim 2: Create an in vitro assay to explore molecular and functional consequences of human pLMs at the single-cell level, considering self-renewal and changing microenvironments. Aim 3: Identify drugs targeting human preleukemic HSPCs through a high-throughput drug screen of human preL-HSPCs. This novel approach aims to pave the way for targeted early interventions. To make these goals feasible the Shlush lab made three major steps forward: 1) created the first reference map of peripheral blood (PB) HSPCs from 150 healthy individuals. 2) developed a dynamics bone marrow in a dish allowing the study of human preL-HSPCs. 3) developed the apoptosis score for detecting apoptosis in a small number of preL-HSPCs.

Mots-clés : clonal hematopoiesis,preleukemic mutations,drug screen,single cell rna sequencing,myeloid malignancies
Projet ERC : VerNisQDevS (Horizon Europe, appel 2022, Consolidator 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 : 1821750.0 €

Quantum computing is undergoing a phase transition, as the field shifts from asking “what if” (quantum computers existed) to ``how do'' (we leverage the power of emerging quantum devices). Progress in the design of experimental quantum systems raises a unique challenge: given that their size already precludes direct classical simulation, and given that quantum states are perturbed by observation, how does one test and certify the new devices? This difficulty is starkly evidenced by the ongoing race for demonstrating a quantum computational advantage. Given that the task cannot be replicated classically, can it be verified? The main goals of this project are to develop effective means to characterize, certify and harness complex quantum states and devices. To achieve this we employ the framework of interactive proofs from classical complexity theory. We use this to model interactions as varied as demonstrations of quantumness, the delegation of a quantum computation, or cryptographic tasks such as quantum key distribution. The major challenges that we address are scalability, noise tolerance, and security. To achieve scalability we build on complexity-theoretic techniques such as the notion of probabilistically checkable proofs. We focus on the design of protocols that successfully complete even when the quantum device is slightly noisy. The security notions that we seek encompass device independence (no a priori trust is placed on the quantum equipment) and side information (privacy should be guaranteed with respect to any external party). Large-scale experimental demonstrations of quantum networks are currently being planned in many countries, including a leading European effort (EuroQCI). Our work lays the theoretical groundwork for scalable, secure and trustworthy interactions in such networks. It paves the way to making the power of quantum devices for computation and communication available to a wider public remotely and through classical means.

Mots-clés : quantum interactive proofs,verification,self testing,device independence
Projet ERC : SharpOS (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
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 : 1787660.0 €

O-minimality is a model-theoretic formalism of tame geometry. Sets that are definable in o-minimal structures enjoy strong finiteness properties, such as the existence of finite stratifications and triangulations. While drawing inspiration from the classical areas of semialgebraic and subanalytic geometry, o-minimality encompasses a strictly larger range of structures - most notably structures defined using the logarithmic and exponential functions. In the past 15 years o-minimality has enjoyed a golden age, as deep connections relating these larger structures to arithmetic geometry and Hodge theory have been unfolding. However, over this period it has become clear that some finer aspects of tameness, especially as it relates to arithmetic, are not accessible in the full generality of o-minimal theory. Some prominent conjectures have been formulated only for specific structures, with a folklore expectation that they should hold in all structures naturally arising in algebraic and arithmetic geometry.  In this project we propose to refine the foundation of o-minimal geometry by introducing a notion of "sharply o-minimal structures'', with the goal of capturing the finer arithmetic properties of the definable sets arising in algebraic and arithmetic geometry. We argue that this should be achieved by postulating sharper estimates for the asymptotic interaction between definable and algebraic sets. The construction of such "sharp" structures has until recently seemed technically unattainable, but three recent technical developments, including the first example of a sharply o-minimal structure beyond the semialgebraic case, renders the project timely and potentially feasible. We show how many recent advances in the area point to sharp o-minimality as a possible grand unifying framework, and illustrate how a realization of this program would greatly simplify, strengthen and generalize many of the state of the art applications of o-minimality.

Mots-clés : o minimal geometry,diophantine geometry,andre oort conjecture,pila wilkie theorem
Projet ERC : ExUteroEmbryogenesis (Horizon Europe, appel 2022, Consolidator 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 : 2000000.0 €

Studying early human development is crucial for understanding embryonic defects and learning developmental principles that can be applied in differentiation of human iPSCs into relevant cells for transplantation. Such research requires large numbers of human embryos, however justified ethical barriers makes this impossible. Since the mouse has been a “guiding compass” for all revolutionary technologies applied with human pluripotent stem cells, here we seek to develop biotechnologies in mice, rabbits and non-human primates (NHP) that will likely enable in the future, conceptually and technologically, circumventing this problem in humans. A two-pronged biotechnological platform development will be pursued: 1)Engineering devices that enable ex utero culture of mammalian embryos from pre-implantation until complete organogenesis 2)Establishing platforms in which in vitro expanded stem cells can be coaxed to generate synthetic embryo-like structures (embryoids), that can self-organize and be grown in the latter developed ex utero embryogenesis devices, to yield structures with both embryonic and extra-embryonic compartments, that capture advanced embryonic patterns. Motivated by our recently devised platform that allows natural mouse embryogenesis from post-implantation until organogenesis ex utero, we now aim to develop and validate biotechnological platforms that capture entire stages of development from pre-implantation until completion of organogenesis in natural mouse and rabbit embryos ex utero, and transform this knowledge to engineer advanced synthetic embryoids from in vitro expanded mouse, rabbit and NHP stem cell populations. We will utilize in-house engineered devices, stem cell-based models, cutting-edge gene editing, microscopy, optogenetics and single cell biology. Our work will establish novel platforms for generating advanced self-organizing embryoids ex utero, that can be used for stem cell differentiation, drug screening and disease modeling.

Mots-clés : stem cells,induced pluripotent stem cells ipscs,embryogenesis,ex utero embryogenesis,human ips disease modeling,synthetic embryos,artificial embryos,optogenetics,embryonic stem cells,transgenics,tetraploid complementation and micro injections,chimeric animals,stem cell programming and reprogramming,pluripotency,trophoblast stem cells tscs,primitive endoderm cells pre and xen cells,blastocyst
Projet ERC : EmbryoCellEnsemble (Horizon Europe, appel 2023, Consolidator 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 : 2000000.0 €

In multicellular orIn multicellular organisms, how variation is achieved while cells comprise identical genetic information represents a fundamental open challenge my group strives to engage in the coming years. The development of a single fertilized egg into a complete embryo represents an especially beautiful embodiment of this problem. The process of differentiation is defined by the capacity of the cell ensemble to acquire increasingly more specialized internal states in a coordinated fashion. We are therefore excited by recent breakthroughs in single-cell transcriptomics and epigenomics since these can capture the emergence of embryonic cellular diversification at incredible resolution. But, we believe there is an urgent need in the field to match descriptive single cell atlases with models and experimental frameworks to derive novel understanding of function and regulation in this process. To this end, we will undertake three complementary approaches – all implemented during specification of the basic mammalian body plan (gastrulation) in vivo. (i) We will scrutinize parallel and converged differentiation in embryonic and extraembryonic lineages at absolute time. This will be achieved in both mouse and rabbit, providing unprecedented molecular insight into the evolutionary hourglass theory. (ii) Building on our recently developed capabilities, we will systematically dissect epigenetic mechanisms shaping and memorizing intracellular states. Importantly, we will do so by controlling for cell type and effects that propagate in and between tissues over time. (iii) Finally, we will chart and manipulate extracellular signaling affecting cell specification in the 3D embryonic space. Our study will provide mechanistic understanding and much-needed quantitative models that truly represent embryonic development as a concurrent interacting ensemble with far-reaching implications for other fields, such as regenerative medicine, cancer, aging, and synthetic embryogenesis.

Mots-clés : systems biology,single cell genomics,embryonic stem cells,transgenics,mammalian gastrulation,species comparison
Projet ERC : CovProximity (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
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 : 1998744.0 €

Chemical biology has made remarkable strides over recent decades, producing potent and selective inhibitors for many proteins, including essential drug targets. Despite these achievements, however, inhibition has been the primary mode of perturbation (GPCRs notwithstanding), whereas many biological processes are controlled through a rich spectrum of biochemical perturbations. What if a small molecule could activate an enzyme? Install or remove a post-translational modification (PTM)? Or control its oligomeric state?  The overarching goal of this proposal is to dramatically increase the scope and breadth of perturbations and PTMs one can induce in cells using small molecules. Accomplishing this will have tremendous impact on the ability to investigate numerous cellular processes and holds massive therapeutic potential. To achieve this goal, we will build on our recently developed Covalent Ligand-Directed Release (CoLDR) chemistry, which allows to tag proteins covalently while preserving their function. Our research will develop:  1. a general method to create CoLDR-based probes against a panel of targets, that would enable us to harness their activity for selective perturbation of new, non-endogenous, substrates. 2. homo-dimeric CoLDR probes to induce selective dimerization of targets. This will allow us to selectively activate targets such as kinases in cells. We will also design protein polymerizers, by tethering obligatory homodimers. 3. chimeric proximity inducers that would selectively modify new targets in vitro and in cells.  Our group’s experience in covalent chemical biology, proteolysis-targeting chimeras, and the development of the CoLDR platform, makes us uniquely positioned to create the next generation of covalent proximity inducers.

Mots-clés : covalent fragments,covalent inhibitors,covalent kinase inhibitors,protein proximity inducers,protacs,phics
Projet ERC : NEURi3D (Horizon Europe, appel 2023, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer Science and Informatics
Entité participante : Université technique de Crète — Pays : Grèce — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Visualizing our surroundings and imagination has been an integral part of human history. In today's era, we have the privilege to immerse in 3D digital environments and interact with virtual objects and characters. However, creating digital representations of environments (i.e., 3D models) often requires excessive amount of manual effort and time even for trained 3D artists. Over the recent years, there have been remarkable advances in deep learning methods that attempt to reconstruct 3D models from real-world data captured in images or scans. However, we are still far from automatically producing 3D models usable in interactive 3D environments and simulations i.e., the resulting reconstructed 3D models lack controllers and metadata related to their articulation structure, possible motions, and interaction with other objects or agents. Automating the synthesis of interactive 3D models is crucial for several applications, such as (a) virtual and mixed reality environments where objects and characters are not static, but instead move and interact with each other, (b) automating animation pipelines, (c) training robots for object interaction in simulated environments, (d) 3D printing of functional objects, (e) digital entertainment. In this project, we will answer the question: "how can we automate the generation of interactive 3D models of objects and characters?". Our project will include the following thrusts: (1) We will design deep architectures that automatically infer motion controllers and interaction-related metadata for input 3D models, effectively making them interactive. (2) We will develop learning methods that replace dynamic real-world objects and characters captured in scans and video with high-quality, interactive, and animated 3D models as digital representatives. (3) We will develop generative models that synthesize interactive 3D objects and characters automatically, and further help reconstructing them from scans and video more faithfully.

Mots-clés : 3d modeling,3d deep learning,animation,reconstruction,generative models
Projet ERC : FOCUS (Horizon Europe, appel 2021, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Nederlandse organisatie voor wetenschappelijk onderzoek — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NWO
Type d'entité : Recherche
Financement ERC de l'entité : 2998125.0 €

There is an urgent need to use solar energy to produce electricity, fuels and chemicals. However, the highly diffuse nature of sunlight in angle, wavelength and space complicate its high-efficiency, low-cost and scalable conversion. FOCUS will develop thin-films that concentrate sunlight in these three aspects, creating collimated, monochromatic, high-intensity beams that can provide advantages for photovoltaics and photocatalysis. The underlying concept is a radically different design for a luminescent solar concentrator (LSC). Conventional LSCs use an emitter-doped plastic or glass sheet as a waveguide, concentrating direct and diffuse sunlight via total internal reflection of fluorescence. The losses associated with reabsorption, emission into the waveguide escape cone and Stokes shift have limited LSC efficiency to 7%. I will eliminate the waveguide completely and replace it with nanophotonic lenses, solving the longstanding problems with LSCs. The key challenges for successful implementation are addressed in three work packages. Nanophotonic design (WP1) will give FOCUS foils that absorb broadband sunlight from all angles, funnel the excitons to lower bandgap nanoscale emitters and concentrate the collimated fluorescence outside of the film. Material learning (WP2) and reciprocity-inspired photosynthesis will use the desired emission pattern to train a material to emit from self-optimized positions, leading to FOCUS foils that learn the desired optical output. Ultrafast 3D nanoprinter (WP3) development will lead to a microscope that synthesizes emitters directly within a solid-state host, tracks their performance (quantum yield, angular emission pattern) in real-time and watches excited carriers relax into directionally emitting states. My track record in nanophotonic solar cells and directional emission combined with my network of leading collaborators put me in an excellent position to achieve these goals.

Mots-clés : luminescent solar concentrators,nanophotovoltaics,nanoscale solar cells,halide perovskites
Projet ERC : MOORELIGHT (Horizon Europe, appel 2022, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and Communication Engineering
Entité participante : Nederlandse organisatie voor wetenschappelijk onderzoek — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NWO
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Advanced semiconductor devices are produced using extreme ultraviolet (EUV) light at just 13.5nm wavelength. This small wavelength enables patterning the smallest and smartest features on chips. The recent revolutionary introduction of EUV lithography (EUVL) was the culmination of several decades of collaborative work between industry and science – a Project Apollo of the digital age. EUVL is powered by light that is produced in the interaction of high-energy CO2-gas laser pulses with molten tin microdroplets. The use of such lasers however leads to unsustainably low overall efficiency in converting electrical power to useful EUV light: delivering a watt of EUV power at the silicon wafer level currently has a megawatt footprint. Replacing gas lasers with much more efficient solid-state lasers will significantly reduce this footprint. It is currently however unclear what laser wavelength, and what plasma ‘recipe’ should be used. This is because we lack understanding of the underlying complex physics.  MOORELIGHT will deliver the missing insight that is required to efficiently and reliably power next-generation solid-state-laser-driven EUV light sources. (1) We will obtain understanding of phase changes and fragmentation of laser-impacted liquid thin tin targets and develop capabilities for laser-tailoring targets. (2) We will use tailored targets to investigate how these couple to laser light of variable wavelength and spatiotemporal profile to produce hot-and-dense plasma. This will provide insight through experiments and modeling into the optimum plasma recipe for producing EUV light, in tandem with efforts (3) to advance predictive plasma modeling by finding the elusive, atomic origins of the EUV light. Individually, these objectives will significantly impact their related fields of science and technology. Combined, they will enable to sustainably power tomorrow’s EUVL, and help realize the EU’s ambitions regarding its technological leadership in nanotechnology.

Mots-clés : extreme ultraviolet light,euv lithography,laser produced plasma,laser matter interaction,spectroscopy,fluid dynamics,highly charged ions,electron beam ion trap