Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : XlinkRepair (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Royal Netherlands Academy of Arts and Sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

DNA interstrand crosslinks (ICLs) are toxic DNA lesions that are induced by cancer chemotherapeutics but are also formed endogenously. ICL repair is mostly linked to DNA replication, which complicated the biochemical dissection of this process. The classical ICL repair pathway is the Fanconi anemia pathway, affected in the cancer predisposition syndrome Fanconi anemia (FA). Although the repair mechanism is poorly understood, recent studies have revealed unanticipated insights that now allow us to address key questions. While the FA pathway was long thought to be the only replication-coupled ICL repair pathway, two novel pathways were recently discovered. We described one novel pathway that repairs endogenous ICLs induced by acetaldehyde, a product of alcohol metabolism. However, mechanistic details of this novel pathway are lacking. Other unexplored aspects are the role of the chromatin context and the mutagenic consequences of repair. Here, I will capitalize on my group’s expertise applying a unique biochemical system that recapitulates ICL repair, and combine this with newly developed tools to address these objectives: 1) We will decipher key steps in the FA pathway of ICL repair. We will resolve the roles(s) of the FA core complex and the direct function of FANCI-FANCD2 ubiquitination, a key activating step. 2) We will move into new directions and investigate FA-independent ICL repair pathways. We will determine the molecular mechanism of acetaldehyde ICL repair and investigate the repair mechanisms of other aldehyde-induced ICLs. 3) We will extend our knowledge beyond the direct repair factors by defining chromatin dynamics during ICL repair and determining its role. In addition, we will delineate the mutagenicity of ICL repair to evaluate its consequences. These studies will provide important novel insights into how cells maintain genome integrity, increase our understanding of Fanconi anemia, and may improve strategies in chemotherapeutic treatment.
Projet ERC : EmbryoMethFunc (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

DNA methylation is essential for normal mammalian development. While seminal work has provided tremendous insight into the dynamic regulation of DNA methylation throughout embryogenesis, comprehensive understanding of how cell-specific methylation programs are established and maintained, and how they are involved in defining cell states in vivo through regulation of target genes, remains a formidable task. Revolutionary technologies now offer unprecedented opportunities for understanding the function of DNA methylation in specifying, memorizing and modulating embryonic programs. These powerful tools motivate further development of novel experimental systems, to integrate single-cell monitoring with flexible engineering of markers, reporters and perturbations. This will make it possible to precisely target key rare embryonic cell populations for in-depth analysis. Here, combining cutting-edge methods for single cell mapping of DNA methylation and gene expression, and by developing a novel approach for inferring spatial information from single cell genomic data, we propose to comprehensively chart the post-implantation embryo, at unprecedented resolution. To move to functional studies, we will implement our recently established reporter system that enables monitoring and isolation of cells based on endogenous locus-specific changes in DNA methylation. Together with site-specific methylation editing tools, mouse genetics, and in vitro differentiation of pluripotent stem cells, we will study the developmental potential of rare epiblast cells that we identified that exhibit lower-than-expected genome-wide methylation levels. We will further study the effects of cell-specific methylation changes at an imprinted control region on gene dosage by genetic and epigenetic perturbation, during mouse development. Our combined approach will open new avenues for elucidating the contribution of cell-specific DNA methylation changes to cell-state and function following implantation

Mots-clés : dna methylation,genome and epigenome editing,single cell rna and dna methylation sequencing,mouse development,spatial reconstitution,parental imprinting,transgenics,locus specific reporters
Projet ERC : RepTime (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999784.99 €

DNA replication is an essential process ensuring the transmission of genetic information and is highly regulated. Specifically, the DNA replication-timing program ensures that the sites of initiation of DNA replication, termed origins, are not all activated simultaneously but follow a cell-type specific schedule. This pathway is conserved throughout eukaryotic evolution, however its molecular control and biological role are not fully understood. In this proposal I aim to understand key aspects of replication-timing program by employing a combination of advanced mouse genetics, genomics, cell biology and proteomics. Currently one of the major limitations in the mammalian DNA replication field is the elusive identity of origins. I aim to comprehensively map origins in a variety of mouse cells/tissues and relate the regulation of origin firing to the control of gene expression and three-dimensional nuclear architecture. I have discovered that Rif1 controls replication timing and links it to nuclear three-dimensional organization. I have also revealed the existence of a novel Rif1-independent pathway that controls the timing of a significant fraction of the late-replicating genome, identified by constitutive association with a key nuclear architecture component, Lamin B1. Here, I propose complementary approaches to understand the molecular mechanism by which Rif1 coordinates replication timing and nuclear organization as well as the molecular underpinnings of the novel pathway instructing late-replication in Lamin B1-associated regions. Finally, my goal is to understand the in vivo biological role of the replication-timing program. Our preliminary data identify mammalian X inactivation as a process where replication timing may play a fundamental part. My ultimate objective is to contribute to the realization of a comprehensive understanding of nuclear function, integrating the co-regulation of DNA replication with gene expression, epigenetic inheritance and DNA repair.

Mots-clés : chromosome biology,nuclear organization,dna replication
Projet ERC : EpigeneticScars (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Ben-Gurion University of the Negev — Pays : Israël — Rôle : PI
Acronyme de l'entité : BGU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

DNA safekeeping is one of the most important functions of the cell. Since DNA damage occurs in the context of chromatin, it affects both the DNA itself, but also the epigenetic landscape. While the repair mechanism of the DNA has been extensively studied, questions abound regarding the restoration of the epigenetic landscape, and the long-term effects that damage leaves in the region. In this proposal I aim to address these questions using modified DSBs repair sensors from different pathways such as “homologous recombination” and “non-homologous end joining” to map the repair process. Our method will allow us to investigate the influence of the natural epigenetic landscape on pathway choice, the dynamic process of repair and the restoration of the region. Moreover, we will investigate whether certain repair processes leave long- lasting effects at the site of damage or even “epigenetic scars”. The advantage of our method is that it allows us to map each sensor repair time-line in an unbiased and high throughput manner over extended periods of time, even once the damage is already repaired. These questions are especially important for our understanding of ageing, and age-related diseases that are driven by DNA damage. Last, we will test the long-lasting effects of past damage in two different contexts: animal models of neurodegeneration, where DNA damage accumulates, and in the efficiency of reprograming to produce healthy induced pluripotent stem cells (IPCs).

Mots-clés : double strand break repair,epigenetic signaling,dna damage response,ageing,dna damage sensor
Projet ERC : DPC_REPAIR (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498856.0 €

DNA-protein cross-links (DPCs) are common DNA lesions caused by endogenous, environmental, and chemotherapeutic agents. Cells are susceptible to these lesions during S phase, as DPCs impede replication fork progression and are likely to induce genomic instability, a cause of cancer and aging. Despite its relevance to human health, the repair of DPCs is poorly understood. Research on DPC repair has mainly involved testing cellular responses to compounds such as formaldehyde, but these agents induce a wide variety of DNA lesions, and conflicting results have been reported. To overcome these obstacles, I have developed the first in vitro system that recapitulates replication-coupled DPC repair. In this system, a plasmid containing a site-specific DPC is replicated in Xenopus egg extracts. Using this approach, I demonstrated that DPC repair requires DNA replication. When a replication fork encounters a DPC, the DPC is degraded into a peptide-adduct, which allows replication bypass by translesion DNA synthesis. Importantly, these experiments identified a novel proteolytic pathway whose activity is regulated by replication. This in vitro system now provides a powerful means to identify and characterize the different factors that participate in S phase DPC repair. I speculate that for DPC processing to occur, the protein-adduct must first be detected, then marked for degradation and ultimately degraded. Using a series of complementary strategies, which will take advantage of the in vitro system combined with proteome and genome wide approaches, I seek to uncover the different players that participate in each of these events. This project will enable a detailed mechanistic outlook of a complex multi-step reaction that has not been feasible to achieve using existing methodologies. It will also improve our understanding of how DPCs impact genomic stability and the consequences of not repairing these lesions for human health.

Mots-clés : dna cross link repair,dna replication,protein degradation,ubiquitin signaling
Projet ERC : DREAM (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Centre Marc Bloch — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : CMB
Type d'entité : Recherche
Financement ERC de l'entité : 54200.0 €

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 : ArsNova (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Florence — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1255875.0 €

Dante Alighieri at the dawn of the 1300s, as well as Eustache Deschamps almost a century later, conceived poetry as music in itself. But what happens with poetry when it is involved in the complex architecture of polyphony? The aim of this project is to study for the first time the corpus of 14th- and early 15th-century poetry set to music by Ars Nova polyphonists (more than 1200 texts). This repertoire gathers different poetic and musical traditions, as shown by the multilingual anthologies copied during the last years of the Schism. The choice of this corpus is motivated by two primary goals: a) to offer a new interpretation of its meaning and function in the cultural and historical context, one that may be then applied to the rest of coeval European lyric poetry; b) to overcome current disciplinary divisions in order to generate a new methodological balance between the project’s two main fields of interest (Comparative Literature / Musicology). Most Ars Nova polyphonists were directly associated with religious institutions. In many texts, the language of courtly love expresses the values of caritas, the theological virtue that guides wise rulers and leads them to desire the common good. Thus, the poetic figure of the lover becomes a metaphor for the political man, and love poetry can be used as a device for diplomacy, as well as for personal and institutional propaganda. From this unprecedented point of view, the project will develop three research lines in response to the following questions: 1) How is the relationship between poetry and music, and how is the dialogue between the different poetic and musical traditions viewed in relation to each context of production? 2) To what extent does Ars Nova poetry take part in the ‘soft power’ strategies exercised by the entire European political class of the time? 3) Is there a connection between the multilingualism of the manuscript tradition and the perception of the Ars Nova as a European, intercultural repertoire?

Mots-clés : medieval latin and romance philologies and literatures,history of collective identities,history of philosophy,religious studies,symbolic representation,lexicography,digital humanities
Projet ERC : DAMIC-M (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
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 : 3349563.0 €

Dark matter (DM) is a ubiquitous yet invisible presence in our universe. It dictated how galaxies formed in the first place, and now moves stars around them at puzzling speeds. The DM mass in the universe is known to be five times that of ordinary matter; yet its true nature remains elusive. Weakly interacting massive particles (WIMPs), relics from the early universe, are a compelling explanation chased by sensitive experiments in deep underground laboratories. However, searches for heavy WIMPs (≈100 times the proton mass), the most theoretically natural candidates, have been so far unsuccessful. Nor has evidence for such heavy particles yet been found at the CERN Large Hadron Collider. Alternative scenarios are now under scrutiny, such as the existence of a hidden sector of lighter DM particles that interact, differently than WIMPs, also with electrons. DAMIC-M (Dark Matter In CCDs at Modane) will search beyond the heavy WIMP paradigm by detecting nuclear recoils and electrons induced by light DM in charge-coupled devices (CCDs). The 0.5 kg detector will be installed at the Laboratoire Souterrain de Modane, France. In this novel and unconventional use of CCDs, which are commonly employed for digital imaging in astronomical telescopes, the ionization charge will be detected in the most massive CCDs ever built with exquisite spatial resolution (15 μm x 15 μm pixel). The crucial innovation in these devices is the non-destructive, repetitive measurement of the pixel charge, which results in the high-resolution detection of a single electron and unprecedented sensitivity to light DM (≈ eV energies are enough to free an electron in silicon). By counting individual charges in a detector with extremely low leakage current – a combination unmatched by any other DM experiment – DAMIC-M will take a leap forward of several orders of magnitude in the exploration of the hidden sector, a jump that may be rewarded by serendipitous discovery.

Mots-clés : dark matter,hidden sector
Projet ERC : Xenoscope (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UZH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3344108.0 €

Dark matter is one of the greatest mysteries in the Cosmos, as its intrinsic nature is largely unknown. The identification and characterization of dark matter particles is a major endeavor in physics. XENOSCOPE will be a unique project focussed on essential, cutting-edge research towards a multi-ton dark matter detector using liquid xenon (LXe) as target material. With its low energy threshold, ultra-low backgrounds and excellent energy resolution, a LXe observatory will be highly sensitive to other rare interactions, such as from solar and supernova neutrinos, double beta decays of 136Xe, as well as from axions and axion-like particles. To design and construct a 50 t (40 t in the time projection chamber, TPC) detector, a number of critical technological challenges must first be addressed. Fundamental aspects are related to the design of the TPC, including the identification of new photosensors, the optimization of the light and charge collection (hence the energy threshold and resolution), and the minimization of radioactive backgrounds. XENOSCOPE will address all these aspects through a number of small, medium-size and a full-scale (in the z-coordinate of the TPC) prototypes. The goal is to specify the required input for the technical design of the 50 t detector, to be realized by the DARWIN consortium which the PI leads. Arrays of VUV-sensitive SiPMs will be studied as novel light sensors, and a 4-π photosensor coverage TPC will be constructed for the first time. Signal detection will be optimized for both low and high-energy readout, thus drastically increasing the dynamic range of a LXe-TPC. Low-background materials will be identified and characterized not only for the photosensors and their read-out, but for all the components of the detector. Finally, a full scale TPC in the z-dimension, 2.6 m in height, will be designed, built and operated and electron drift and extraction into the vapor phase over such large distances for the first time demonstrated.

Mots-clés : direct dark matter detection,neutrinoless double beta decay,solar neutrinos,noble liquid techniques,liquid xenon time projection chamber
Projet ERC : ExtraLytics (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 148377.0 €

Data is becoming the key to effective decision making in more and more aspects of modern society. Big data analytics provide insight into complex processes considering a breadth of factors. This promises to increase the efficiency of decision making in areas such as policy making, research, product development, or financial and retail markets. Currently, big data analytics is employed only by technologically savvy organisations with control over the relevant data. This further exacerbates the information asymmetry that has been plaguing many of these areas: real estate where buyers have long suffered from limited information, often controlled by the seller; or retail markets where sellers are now employing sophisticated competitive price intelligence solutions unaffordable to buyers. Who can tell you if it is better to buy a house with a garden or with a garage; or where renovations will yield more rent over time? ExtraLytics answers these questions through a combination of big data extraction and analytics. ExtraLytics introduces analytics and prediction models into DIADEM’s platform for accurate big data extraction from the web, which is able to extract required data at massive scale from the web. For the proof-of-concept, ExtraLytics initially focuses on residential real estate in the UK, a £4,135bn market (UBS), where buyers and renters are required to make fast decision with limited information—time on market is often below a week or even below a day as for desirable rentals in Oxford. “In an age when ‘big data’ is shaping our every move, how come an industry that takes so much profit can’t keep pace with technology and use it to actually deliver a service worth the money they take in commission?” (The Telegraph). ExtraLytics addresses this lack of data-driven analytics by giving consumers and investors alike a tool for better understanding properties, their location, their neighborhood, and their investment potential compared to other properties.

Mots-clés : decision support,data extraction,real estate,prediction models