Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : LASSO (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Aalborg University — Pays : Danemark — Rôle : PI
Acronyme de l'entité : AAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2493750.0 €

Cyber-physical systems (CPS) are emerging throughout society, e.g. traffic systems, smart grids, smart cities, and medical devices, and brings the promise to society of better solutions in terms of performance, efficiency and usability. However, CPS are often highly safety critical, e.g. cars or medical devices, thus the utmost care must be taken that optimization of performance does not hamper crucial safety conditions. Given the constant growth in complexity of CPS, this task is becoming increasingly demanding for companies to handle with existing methods. The principle barrier for mastering the engineering of complex CPS being both trustworthy and efficient is the lack of a theoretical well-founded framework for CPS engineering supported by powerful tools, that will enable companies to timely meet increasing market demands. With his extensive contributions to model-driven methodologies, and as provider of one of the “foremost” tools for embedded systems verification, the PI is well prepared to provide the missing framework. The LASSO framework will support the quantitative modeling of both cyber- and physical components, their efficient analysis, the learning of models for unknown components, as well as automatic synthesis and optimization of missing cyber-components from specifications. LASSO will provide the new generation of scalable tools for CPS, allowing trade-offs between safety constraints and performance measure to be made. LASSO will achieve its objective by ground-breaking and extensive combinations of two different research areas: model checking and machine learning. The framework will develop a complete metric approximation theory for quantitative models, allowing properties to be inferred from reduced or learned models with metric guarantees of their validity in the original system. Further, the applicability of the framework will be validated through a number of CPS case studies, and the tools developed will be made generally available.

Mots-clés : model checking,statistical model checking synthesis,automata learning,graphical models
Projet ERC : METHYLEVOL (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499965.0 €

Cytosine DNA methylation is a major component of eukaryotic chromatin, yet extensive variation of methylation patterns occurs throughout eukaryotes. So far, the roles of DNA methylation have been mostly characterized in vertebrates, plants and fungi, where two common patterns have emerged as potentially ancestral within eukaryotes: methylation of silent transposable elements and methylation of constitutively transcribed genes (gene body methylation). However, the genes responsible for depositing methylation are not always orthologous across divergent lineages, so these common patterns could instead be the product of convergent evolution. To discern between these alternatives, we first need to correct the taxon sampling bias that hampers our understanding about the evolution of DNA methylation. In this project we will determine the roles of DNA methylation across vastly underexplored eukaryotic diversity. We will use state-of-the-art genomic techniques, experimental manipulations and computational analyses to trace the evolutionary conservation of methylation-dependent transposable element silencing across a wide range of unicellular eukaryotes, using methylation-depleting drugs and bisulfite sequencing. We will then assess the roles of gene body methylation in an invertebrate to unveil similarities with plants and shed light on why vertebrates transitioned to hypermethylated genomes. Finally, we will study the evolution of proteins able to bind and interpret DNA methylation across disparate eukaryotes, since ultimately these proteins link DNA methylation and its regulatory functions. Through linking experimental epigenomics to macro-evolutionary comparative genomics this project will reveal how different functions of DNA methylation assembled throughout evolution. In turn, this evolutionary perspective will allow a better understanding of the genome regulatory roles of this base modification and its impact on genome composition in plants and animals.

Mots-clés : dna methylation,eukaryotic evolution,macro evolution,transcription factor,evolutionary developmental biology,chromatin evolution,comparative genomics
Projet ERC : SexMeth (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 164728.75 €

DNA methylation is an epigenetic mechanism carrying regulatory information across generations in plants and animals. Germlines – called sexual lineages (SLs) in plants – are essential for understanding methylation-based epigenetics because they mediate inheritance and undergo large-scale methylation reprogramming. Germline methylation reprogramming is also crucial for reproduction. However, our understanding of plant SL epigenetics is in its infancy. I have done some of the first and most influential work in plant SL epigenetics, and developed advanced techniques for the isolation and epigenomic analysis of rare plant cell types. Recently my lab discovered that the small RNA-directed DNA methylation pathway, which generally only targets transposons, induces methylation of genes specifically in SLs, thereby regulating gene expression and meiosis. Our results also indicate that genic methylation is established in meiocytes (the origin of the male SL) by soma-derived small RNAs that are attenuated by heat stress, suggesting the hypothesis that environmentally malleable heritable information flows from soma to the germline. We will test our hypothesis and reveal the molecular mechanisms underlying SL-specific DNA methylation in plants by pursuing the following objectives: 1. Determine how SL-specific genic methylation is established in meiocytes 2. Reveal how sRNA biogenesis and transport mediate DNA methylation in the male SL 3. Elucidate environmental modulation and transgenerational inheritance of SL methylation Our research will reveal how new genomic loci become methylated and stay methylated through cell divisions, and how methylation is adjusted by the environment and carried to the next generation to influence phenotype. This knowledge will revolutionize our understanding of developmentally regulated methylation reprogramming, and will be invaluable for site- and/or cell type- specific engineering of DNA methylation.

Mots-clés : dna methylation,sexual reproduction,arabidopsis
Projet ERC : GeneBodyMethylation (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

DNA methylation, the covalent binding of a methyl group (CH3) to cytosine base, regulates the genome activity and plays a fundamental developmental role in eukaryotes. Its epigenetic characteristics of regulating transcription without changing the genetic code together with the ability to be transmitted through DNA replication allow organisms to memorize cellular events for many generations. DNA methylation is mostly known for its role in transcriptional silencing; however, its functional output is more complex and is influenced in part by its DNA context. Recent genomic studies, have found DNA methylation to be targeted inside sequences of actively transcribed genes, thus termed gene body methylation. Despite being an evolutionary conserved and a robust methylation pathway targeted to thousands of genes in animal and plant genomes, the function of gene body methylation is still poorly understood at both the molecular and functional level. Similar to the chicken and egg conundrum, because we do not know what gene body methylation does, therefore scientists could not apply its function to discover its regulators either. Gene body methylation is targeted to a very specific subset and subregions of genes, thus we strongly believe that specific factors exist and are missing simply because that no one has ever searched for them before. Hence, to make major breakthroughs in the field, our approach is to artificially generate gene-body-specific hypomethylated plants that together with customized genetic and biochemical systems will allow us to discover regulators and interpreters of gene body methylation. Using these unique genetic tools and novel molecular factors, we will be able to ultimately explore the particular biological roles of gene body methylation. These findings will fill the gap towards a full comprehension of the entire functional array of DNA methylation, and to its more precise exploitation in yielding better crops and in treating human diseases.

Mots-clés : dna methylation,gene body methylation,arabidopsis
Projet ERC : REPLICHROMA (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 2388100.0 €

DNA replication is essential to cellular function. During a lifetime, each of us synthesizes a light-year’s length of DNA, but this process is so robust that few of us will develop cancer. In eukaryotes, DNA is packed into chromatin, a hierarchical DNA-protein assembly of which the nucleosome forms the basic unit. Chromatin replication convolves DNA replication with the duplication and reassembly of all DNA-associated proteins. Understanding the coupling between these processes has fundamental implications for epigenetic inheritance and cancer. The goal of this proposal is to gain spatiotemporal insight into chromatin replication by using our biophysical expertise in replication and chromosomal dynamics to build up a mechanistic timeline of the process. We will harness recent advances in the reconstitution of the yeast replisome alongside our novel, high-throughput single-molecule approach to visualize and quantify the collaboration between a single yeast replisome and the histone chaperones to achieve chromatin replication. We will: •Monitor the assembly of the replisome on chromatin and visualize how nucleosomes impact its progression. •Quantify how the replisome and histone chaperones disrupt nucleosomes and retain histones for further processing. •Detect the deposition of newly synthesized histones behind the replisome and reveal the interactions between replisome components and histone chaperones that couple replication to nucleosome assembly. •Report on the phenomenon of epigenetic inheritance by imaging histone recycling between parental and daughter DNA. We will examine its timing and efficiency, the conformations of reassembled nucleosomes, and any preferential recycling to either daughter DNA. This proposal places us in a unique position to make major contributions to the field of chromatin replication, and to provide the field with a powerful tool to investigate topics from fundamental questions in molecular biology to the performance of new cancer drugs.

Mots-clés : dna replication,eukaryotic replication,yeast replication,chromatin,nucleosomes,histone chaperones,nucleosome assembly,single molecule biophysics,fluorescence microscopy,magnetic tweezers
Projet ERC : SIDSCA (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Czech Academy of Sciences — Pays : Rép. Tchèque — Rôle : Partner
Acronyme de l'entité : AVČR;CAS
Type d'entité : Recherche
Financement ERC de l'entité : 664375.0 €

DNA single-strand breaks (SSBs) are the most frequent DNA lesions arising in cells and are a major threat to cell survival and genome integrity, as indicated by the elevated genetic deletion, embryonic lethality, or neurological disease observed if single-strand break repair (SSBR) is attenuated. In particular, SSBR defects are associated with hereditary neurodegeneration in humans, as illustrated by the genetic diseases ataxia oculomotor apraxia-1 (AOA1), spinocerebellar ataxia with axonal neuropathy-1 (SCAN1), and microcephaly with early onset seizures (MCSZ). However, two major questions remain: what are the mechanisms by which SSBs trigger neurodegeneration, and to what extent do SSBs contribute to other genetic and/or sporadic neurodegenerative disease? Based on exciting new data we now propose that the impact of SSBs on neurodegeneration extends beyond rare SSBR-defective diseases to include more common motor neurone diseases (amyotrophic lateral sclerosis) and the genetically dominant spinocerebellar ataxias (SCAs). Ultimately, we suggest that SSBs might also be an etiological factor in normal human ageing. Finally, again based on new data, we propose that SSBs induce neurodegeneration by triggering over-activation of the SSB sensor protein, PARP1; thereby identifying inhibitors of this protein (currently licensed for cancer treatment) as a possible therapy for neurodegeneration. We will now address these hypotheses using a range of cutting edge molecular/cellular techniques. In particular we will (a), systematically examine all relevant amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) and spinocerebellar ataxia (SCA) proteins for involvement in the DNA damage response, (b) Identify the mechanism/s by which ALS and SCA proteins engage in the DNA damage response, (c) Identify the role of ALS and SCA proteins in the DNA damage response, and (d) Explore PARP1 as a possible therapeutic target for treatment of neurodegenerative disease.

Mots-clés : the relationship between dna strand breakage,transcription,and neurodegenerative disease
Projet ERC : TOPOmics (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Spanish National Cancer Research Centre — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CNIO
Type d'entité : Recherche
Financement ERC de l'entité : 259090.94 €

DNA topoisomerases are conserved nuclear enzymes that regulate DNA topology by transiently cleaving and resealing the DNA molecule, fulfilling a fundamental role in virtually every aspect of chromosome metabolism. Nevertheless, erroneous or abortive topoisomerase activity can result in persistent DNA strand breaks with the enzyme covalently attached to 3’ or 5’ DNA ends by a phosphotyrosyl bond, an anomalous structure that can compromise cell survival and/or genome integrity with the consequent implications in tumourigenesis. This peculiarity of topoisomerase catalysis also underlies the anticancer efficacy of topoisomerase poisons, which inhibit the re-ligation step of the reaction inducing the formation of DNA breaks that preferentially target highly proliferating and/or repair defective tumour cells. In addition to this link with cancer therapy, defects in the repair of topoisomerase-induced DNA damage have been linked to neurological disease. Understanding the cellular response to topoisomerase-induced breaks is therefore key for important aspects of human health, with possible implications in the development of novel diagnostic, prognostic and therapeutic tools. This project aims at acquiring a comprehensive picture of the dynamics of topoisomerase-induced DNA breaks: from their occurrence and repair to the consequences for genome expression and integrity. We rely on the development of completely novel assays to detect and isolate the different intermediates of topoisomerase-induced break repair, and which overcome major traditional limitations in the field. These tools are subsequently used to integrate the time-dependent and genome-wide distribution of the different steps and final outcomes of the process of topoisomerase-induced DNA break repair. Furthermore, we outline original proteomic and genetic screenings to identify novel factors and pathways specifically involved the cellular response to this important type of DNA lesion.

Mots-clés : dna damage and repair,dna breaks,dna topoisomerases,genome instability
Projet ERC : DREAM (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Royal Netherlands Academy of Arts and Sciences — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 31250.0 €

DREAM, Drafting and Enacting the Revolutions in the Arab Mediterranean, seeks to write the history of the revolutions in the Arab Mediterranean since the independences. It aims to write a transnational history of often forgotten struggles, recall facts and original forms of resistance. We know very few about the revolts that occurred in this period, and even less about the memory that they left in the societies, the way these memories circulated. This rediscovery of revolutions in the shadows must be done through the collection of original material, specifically “poor archives” of the ordinary and the production of Archives – through a combination of classical interviews and innovative methods that involve researchers, archivists, artists and the actors themselves. The objective is to write a history that focuses on emotions and paths of revolts, telling us more about the link between all dimensions of human lives in these territories (religion, gender, social positions) and the articulation of these dimensions in the revolutionary projects. DREAM aims to write a history that doesn’t produce heroes or big figures, doesn’t discuss success or failure, but tries to understand the motivations and the potentialities that were at stake in different episodes and moments, during the uprisings and in between them. It aims to explore the historical signification and the concrete aspects of the call for dignity (Karama/sharaf) in a space that, after liberating itself from the colonial domination, was trapped into the illusion of a common faith (being it the Arab nation or the Islamic umma) and the concrete oppression of authoritarian regimes. This period needs urgently to be explored and history, with its modern tools and patterns, can embrace and trace the particular conditions in which Arab people lived for more than six decades, and specifically the frames of their dreams and projections.

Mots-clés : arab world,social history,revolutions
Projet ERC : DYBBUK (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1221480.0 €

DYBBUK will uncover and explore the popular theatre that made up the daily cultural reality of the Jewish masses at the turn of the 20th century. It will crack open the textual body of remaining musical and dramatic manuscripts, to the complete performances of this popular theatre. Amid a massive migration movement at the turn of the 20th century, the Yiddish popular theatre prospered, producing a staggering volume of entertainment consumed by millions of Jews. Most of this mass-appealing output was delegitimized by Jewish intellectuals as Shund (trash), a term that encompasses primitive, plagiarized, vulgar, and worthless art. Consequently, a valuable component of modern popular culture has been overlooked. DYBBUK will restore this neglected yet highly influential corpus of Yiddish popular theatre and make it available for our appreciation. Revising canonical cultural paradigms, DYBBUK recognizes delegitimized artistic ‘lowbrow’ theatre as a vital component in the fashioning of modernist culture. Focusing on the unexplored theatrical corpus of the two most prolific Shund authors: Moyshe Hurwitz (1844-1910) and Joseph Lateiner (1853-1935), this project offers an integrative typological, embodied, and theoretical analysis of theatrical themes, forms, and practices. The Yiddish popular theatre played a crucial role in transporting cultural styles, ideas, and products. To untangle and understand the complexity and scope of this theatre, this project devises a groundbreaking analytical and embodied toolkit for studying theatre history. We will incorporate into our analysis resources of various media, and we will reenact a forgotten Shund performance in a practice-based research. In doing so, DYBBUK will transform our understanding of popular theatre, revealing it as a preeminent ethnographic and historical source for examining the sensual and experiential dimensions of theatre, and the theatrical and cultural exchange of minorities with mainstream culture.

Mots-clés : jewish culture,european and american popular culture,popular theatre,modernism,jewish folklore,practice based theatre research,theatre history and historiography,yiddish theatre,yiddish language and culture,jewish immigration,performance analysis,music theatre