Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SYNC_DEV (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Gene expression is precisely controlled in time and space during the development of Metazoan organisms. While numerous studies have established how spatial information is integrated by gene regulatory regions, called enhancers, little is known about the temporal aspects of transcription. Most of our insights into gene regulation stem from the use of fixed preparations where timing is artificially reconstituted from different snapshots. My goal is to integrate the dynamic aspects of transcription to understand how coordination is achieved and whether it is required during development. Transcriptional coordination refers to the inter-nuclear temporal coordination in gene activation (synchrony) and homogeneity in mRNA distribution across a field of coordinately developing cells. Initially we will characterize the mechanisms of transcriptional coordination in the early Drosophila embryo, a model system which allows quantitative imaging and genetic manipulations. However the ultimate goal of the programme is to extend these analyses to later stages of development during complex tissue specification. My team will improve a newly available live imaging technique to address fundamental questions about transcriptional dynamics in a multicellular developing embryo, with three main objectives: 1-examine the effects of promoter sequence and enhancer priming on transcriptional coordination. 2-analyse the inheritance of transcriptional states from mother to daughter cells and identify the bookmarking mechanisms responsible for this memory. 3-explore the functional role of transcriptional coordination for cell fate specification during cardiogenesis. Through the novel integration of the dynamic and quantitative aspects of transcription in a living organism, this study shall connect coordination in transcription to precision in cell specification. Thus, results from this research should have major impact on our understanding of gene regulation during normal development and disease

Mots-clés : development,transcription,coordination,precision,quantitative imaging,live imaging,cell fate decisions
Projet ERC : POLYAMACHINES (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 2016697.0 €

Gene expression is tightly regulated to allow rapid responses to cellular stimuli. In eukaryotes, the 3´ polyA tail of mRNAs plays key roles in post-transcriptional control. The Cleavage and Polyadenylation Factor (CPF), Ccr4–Not and Pan2–Pan3 multiprotein complexes add or remove polyA tails to regulate mRNA stability and efficiency of translation. They control expression of genes in the inflammatory response, miRNA-targeted gene silencing and expression of maternal mRNAs in oocyte development. These processes are deregulated in disease, including cancer and neurological disorders. Although the proteins that add and remove polyA tails are known, their mechanisms are poorly understood. My lab recently established methods to reconstitute the polyA machinery. This led to new insights into the link between transcription and polyadenylation, new understanding of the molecular mechanisms of deadenylation, and details of RNA recruitment. In this proposal, my objective is to understand the molecular basis for polyadenylation and deadenylation of specific mRNAs. This is now possible because of our novel methodological and biological advances. We will determine high-resolution structures of the polyA machinery using electron cryo-microscopy (cryo-EM), reconstitute their biochemical activities in vitro and study their in vivo functional roles. We use this integrated approach to study intact multiprotein complexes, not individual subunits or domains. This involves considerable technical challenges and an investment in developing high quality purifications and new structural methods. I will determine how the four enzymatic activities of CPF are coupled, the mechanisms by which Ccr4–Not targets specific RNAs, and the molecular basis for RNA recognition by Pan2–Pan3. Together, this will provide new biological and technological insights, leading to understanding of fundamental processes in gene expression and the role of polyA tails in disease.

Mots-clés : mrna polya tail,gene expression
Projet ERC : GravBHs (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Barcelona — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2138825.0 €

General Relativity (GR) encompasses a huge variety of physical phenomena, from the collision of astrophysical black holes, to the dynamics (via holography) of strongly-coupled plasmas and the spontaneous symmetry-breaking in superconductors. Black holes play a central role in all this. However, their equations are exceedingly hard to solve. The apparent lack of a generic tunable parameter that allows to solve the theory perturbatively (like the electric coupling constant in electrodynamics, or the rank of the gauge group in large-N Yang-Mills theory) is arguably the single most important obstacle for generic efficient approaches to the physics of strong gravity and black holes. I argue that one natural parameter suggests itself: GR can be defined in an arbitrary number of dimensions D. Recently I have demonstrated that the limit of large D is optimally tailored for the investigation of black holes, classical and potentially also quantum. Explicit preliminary studies have proved that the concept is sound, powerful, and applicable even in four dimensions. This encourages the pursuit of a full-scale program with two major goals: (A) Reformulating GR and Black Hole physics around the large-D limit in terms of an effective membrane theory of black holes, coupled (non-perturbatively in 1/D) to an effective theory for gravitational radiation. (B) Resolution of outstanding problems in gravitational physics, in particular of problems of direct relevance to cosmic censorship (critical collapse, endpoint of black brane instabilities), and of the quantum theory of black holes. With the new tools of (A), a large number of additional problems in black hole physics and in holographic duality can be solved, which guarantee very substantial fallback objectives. These include black hole collisions, black hole phase diagrams, instabilities, holographic dynamics of finite-temperature systems, and potentially any problem that can be formulated in an arbitrary number of dimensions.

Mots-clés : general relativity,black holes,d expansion,effective theories,gravitational radiation,cosmic censorship
Projet ERC : EPGR (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Fondation sciences mathématiques de Paris — Pays : France — Rôle : Partner
Acronyme de l'entité : FSMP
Type d'entité : Recherche
Financement ERC de l'entité : 187500.0 €

General relativity has been introduced by A. Einstein in 1915. It is a major theory of modern physics and at the same time has led to fascinating mathematical problems. The present proposal focusses on two aspects of the evolution problem for the Einstein equations which has been initiated by the pioneering work of Y. Choquet-Bruhat in 1952. The Einstein equations form a nonlinear system of partial differential equations of hyperbolic type whose complexity raises significant challenges to its mathematical analysis. The goal of this project is to strengthen our understanding of two important themes concerning the evolution problem in general relativity. On the one hand, the control of low regularity solutions of the Einstein equations, a topic which is intimately linked with the celebrated cosmic censorship conjectures of R. Penrose, a major open problem in the field. On the other hand, the question of the stability of particular solutions of the Einstein equations in the wake of the groundbreaking proof of the stability of the Minkowski space-time due to D. Christodoulou and S. Klainerman. These directions are extremely active and have recently led to impressive results. More specifically, this project proposes to consider the following two work packages -Going beyond the bounded L2 curvature theorem. This result has been recently obtained by the PI in collaboration with S. Klainerman and I. Rodnianski and is the sharpest result in so far as low regularity solutions of the Einstein equations are concerned. Yet, the fundamental quest towards a scale invariant well-posedness criterion for the Einstein equations remains wide open. -The black hole stability problem. This problem concerns the stability of the Kerr metrics which form a 2-parameter family of solutions to the Einstein vacuum equations. Many results have been obtained concerning various versions of linear stability, but significant challenges remain in order to tackle the nonlinear stability result.

Mots-clés : einstein equations,cauchy problem,low regularity solutions,black hole stability problem
Projet ERC : POLYADAPT (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Ghent University — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1926250.0 €

Generalist (polyphagous) herbivores can feed and reproduce on many different plant species and include some of the most pesticide resistant and notorious pests in agriculture. An evolutionary link between host plant range and the development of pesticide resistance has been suggested. Although crucial for devising efficient crop protection strategies, the mechanisms underlying rapid adaptation are not well understood, especially in generalists. The spider mite Tetranychus urticae is a global pest known to feed on 1,100 different hosts from 140 plant families, including most major crops. With experimental advances and new tools developed for T. urticae, we are now poised for fundamental advances in understanding the molecular genetic make-up of adaption in generalist pests. We will generate a large collection of fully inbred and resistant mite strains and describe the sampled genomic variation in the context of selection and adaptation. We will study gene regulation mechanisms and quantify cis versus trans regulation of gene expression on a genome wide scale. We will then create a unique population resource that will allow us to map master regulators of gene expression and construct a gene-regulatory network of adaptation responsive genes. In a highly replicated experimental evolution study, combined with Bulk Segregant Analysis (BSA), we will uncover, without a prior hypothesis, the genomic loci that underlie complex cases of resistance and plant adaptation. A core set of adaptation genes will be validated by functional expression and high-throughput interaction assays. Further validation will come from the development of genome editing tools. In summary, POLYADAPT will exploit the genomic tools now available for spider mites to elucidate regulatory and causal variants underlying the extreme adaptation potential of polyphagous pests. This will in the long term lead to innovative methods of pest management.

Mots-clés : insecticide resistance,detoxification,xenobiotic metabolism,tetranychus urticae,mode of action,adaptation,molecular acarology,target site resistance,over expression
Projet ERC : PHOTOMECH (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Heidelberg University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2433445.0 €

Generating artificial organs and tissues from stem cells would revolutionize regenerative medicine and open the door to controllable, biology-based robotics. These systems require a physical understanding of cells, specifically their dynamic and adaptive responses to external forces. This “mechanotransduction” is already known to control important cellular functions, and even stem cell differentiation. With the project proposed here, I plan to bring our quantitative understanding of force-controlled cell functions to a new level by a challenging and novel photomechanical cell stimulation approach. It will combine new materials containing photoswitchable molecules with a complex optical system employing intense laser light pulses. By pulsing the laser, we can apply controllable force stimuli on cells through a conformational change of the photoswitchable molecules. I hypothesize that cell functions, such as adhesion, migration and differentiation, have a huge systematic dependency on frequency, duration, history, and intensity of the force stimuli. Importantly, the method I propose applies forces to cells solely via light and does not require genetic modifications. Using this novel strategy for photomechanical stimulation of cellular proteins, we will be able to collect previously unobtainable physical information within cells on multiple size scales, from the single molecule to tissue level. Using the laser like a pen, we will be able for the first time to write cell functions in 3D, imitating the growth of the cellular scaffolds in living creatures: a completely new means of photomechanically controlling multicellular structures. Ultimately, the tools and materials we study in this interdisciplinary project will allow for the writing of multicellular structures in vitro and in vivo by force-induced mechanotransduction in stem cells. It will lead to a paradigm-shift in many fields, from biophysics to regenerative medicine, synthetic biology and biohybrid robotics.

Mots-clés : cellular biophysics,mechanotransduction,biomaterials,responsive materials,stem cell differentiation
Projet ERC : TeloRNAging (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : FIRC Institute of Molecular Oncology — Pays : Italie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2497500.0 €

Genome instability is a hallmark of cellular and organismal aging. Cells evolved a prompt set of actions known as the DNA damage response (DDR) to preserve genome integrity. Until very recently, DDR pathways have been studied as networks of interacting proteins only. We discovered that the full activation of the DDR pathways depends also on long and short damage-induced non coding RNA synthesised from exposed DNA ends of DNA double-strand breaks (DSB). Inhibitory antisense oligonucleotides (ASO) targeting such non coding RNAs in a sequence-specific manner prevent DDR activation at individual genomic sites. Telomeres, the ends of linear chromosomes, are the best characterized genomic sites of preferential DDR activation during aging. Also telomere dysfunction, similarly to DSB, triggers the synthesis of non coding RNA and ASO against them prevent DDR activation at dysfunctional telomeres in cultured cells and in mice. We plan to determine the mechanisms that unleash ncRNA biogenesis upon telomere dysfunction and identify their mechanisms of action in DDR activation. By exploiting our unprecedented ability to inhibit DDR selectively at telomeres, we will determine the specific contribution of telomeric DDR activation to the detrimental phenotypes associated with aging-related disorders.

Mots-clés : telomere,dna damage response,cellular senescence,phase transition
Projet ERC : ChromoCellDev (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Calouste Gulbenkian Foundation — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1492000.0 €

Genome stability relies on accurate partition of the genome during nuclear division. Proper mitosis, in turn, depends on changes in chromosome organization, such as chromosome condensation and sister chromatid cohesion. Despite the importance of these structural changes, chromatin itself has been long assumed to play a rather passive role during mitosis and chromosomes are usually compared to a “corpse at a funeral: they provide the reason for the proceedings but do not take an active part in them.” (Mazia, 1961). Recent evidence, however, suggests that chromosomes play a more active role in the process of their own segregation. The present proposal tests the “active chromosome” hypothesis by investigating how chromosome morphology influences the fidelity of mitosis. I will use innovative methods for acute protein inactivation, developed during my postdoctoral studies, to evaluate the role of two key protein complexes involved in mitotic chromosome architecture - Condensins and Cohesins. Using a multidisciplinary approach, combining acute protein inactivation, 3D-live cell imaging and quantitative methods, I propose to investigate the role of mitotic chromosomes in the fidelity of mitosis at three different levels. The first one will use novel approaches to uncover the process of mitotic chromosome assembly, which is still largely unknown. The second will explore how mitotic chromosomes take an active part in mitosis by examining how chromosome condensation and cohesion influence chromosome movement and the signalling of the surveillance mechanisms that control nuclear division. Lastly we will evaluate how mitotic errors arising from abnormal chromosome structure impact on development. We aim to evaluate, at the cellular and organism level, how the cell perceives such errors and how (indeed if) they tolerate mitotic abnormalities. By conceptually challenging the passive chromosome view this project has the potential to redefine the role of chromatin during mitosis.

Mots-clés : mitosis,aneuploidy,drosophila,chromosome condensation,sister chromatid cohesion,cohesin,condensin
Projet ERC : UMnD (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : Delft University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU Delft
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498148.0 €

Geographic data about urban objects (buildings, roads) is needed to monitor and control processes within modern urban areas (noise, flooding, energy demand-supply). As these processes occur in 3D, urban applications require 3D data and each application requires its own specific semantic and geometric Level of Detail (LoD) of the 3D data. The scientific challenge of this project is that it requires enormous efforts to collect and transform 3D data to make it suitable for a specific application. Urban applications are therefore forced to work mainly in 2D. This reduction causes the loss of important information. A solution is needed to support the reuse of once collected 3D data in multiple applications. I will develop a fundamental solution for providing 3D data at application specific LoDs to solve the current problem of independently acquired and stored LoDs of a 3D urban model. To enforce consistency across dimensions, the LoDs will be modelled as an extra dimension to the 3D spatial dimensions in an integrated 3D+LoD (4D) model. I will use an innovative method that goes far beyond the state-of-the-art by introducing higher dimensional (nD) mathematical models to the well-established domain of cartographic generalisation in 2D. Furthermore, I will study 3D generalisation solutions to derive coarse from fine data and embed these in the 4D model. “Slicing” operations will be developed that reduce the dimensions of the 4D data to generate error-free 3D data at application specific LoDs. LoD is strongly related to map scale, a well-known concept in GIS. However, modelling it as an extra dimension of geographic data is new. In addition, the intermediate results have the potential to advance the field of geo-information technology, such as the ground-breaking extension of the 2D cartographic generalisation domain to 3D. If successful, the 4D approach opens a new horizon for modelling parametrisable aspects of urban environments, which may establish a new research line.
Projet ERC : CERQUTE (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Institute of Photonic Sciences — Pays : Espagne — Rôle : PI
Acronyme de l'entité : ICFO;ICFO-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 1735043.75 €

Given a quantum system, how can one ensure that it (i) is entangled? (ii) random? (iii) secure? (iv) performs a computation correctly? The concept of quantum certification embraces all these questions and CERQUTE’s main goal is to provide the tools to achieve such certification. The need of a new paradigm for quantum certification has emerged as a consequence of the impressive advances on the control of quantum systems. On the one hand, complex many-body quantum systems are prepared in many labs worldwide. On the other hand, quantum information technologies are making the transition to real applications. Quantum certification is a highly transversal concept that covers a broad range of scenarios –from many-body systems to protocols employing few devices– and questions –from theoretical results and experimental demonstrations to commercial products–. CERQUTE is organized along three research lines that reflect this broadness and inter-disciplinary character: (A) many-body quantum systems: the objective is to provide the tools to identify quantum properties of many-body quantum systems; (B) quantum networks: the objective is to characterize networks in the quantum regime; (C) quantum cryptographic protocols: the objective is to construct cryptography protocols offering certified security. Crucial to achieve these objectives is the development of radically new methods to deal with quantum systems in an efficient way. Expected outcomes are: (i) new methods to detect quantum phenomena in the many-body regime, (ii) new protocols to benchmark quantum simulators and annealers, (iii) first methods to characterize quantum causality, (iv) new protocols exploiting simple network geometries (v) experimentally-friendly cryptographic protocols offering certified security. CERQUTE goes at the heart of the fundamental question of what distinguishes quantum from classical physics and will provide the concepts and protocols for the certification of quantum phenomena and technologies.

Mots-clés : quantum information theory,many body physics,quantum foundations,quantum certification,entanglement,bell s theorem,quantum cryptography,quantum networks,randomness,numerical algorithms