Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : FateID (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 €

The establishment of cell type-specific transcriptional programs involves many interconnected regulatory mechanisms acting on different genomic scales. To dissect this multi-layered control of gene expression in detail, I will develop methods that a) measure multiple cellular outputs in single cells, and b) obtain that information in a time-resolved manner. This proposal outlines my approach to study early mouse development at numerous levels, including (but not limited to) transcription, chromatin context, and nuclear organization. In doing so, I expect to shed light on the mechanism behind cell fate specification and the epigenetic states that precede it. I will develop a novel strategy to simultaneously profile many factors involved in gene regulation in the same cell. Its successful implementation will give insight into transcriptional control at unprecedented modality, revealing the causal relationships between histone modifications, spatial positioning within the nucleus, Polycomb group proteins, and others. Next, I will pursue several “molecular memory” strategies to obtain recordings of past regulatory states, followed by multi-omic readouts at later developmental times. Such retrospective analyses enable linking fate decisions to past molecular events in the same cell, thereby permitting careful reconstruction of the molecular trajectories underlying cell fate choice. Finally, these and previously developed single-cell methods will be applied to unravel the gene-regulatory mechanisms that govern lineage determination in early mouse development.

Mots-clés : spatial genome organisation,single cell genomics,epigenetic,nuclear lamina
Projet ERC : CellFateTech (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1876618.0 €

The evolution from a stem cell to differentiated progeny underpins tissue development and homeostasis, which are driven by a multitude of cell fate choices. The transitions underlying these choices are not well understood. There are a number of challenges that must be overcome to achieve this understanding. In the proposed research we will tackle two of the challenges: first, the dynamics of fate choices, i.e. the dependence of transitions on time and inductive signals, remains cryptic; second, mechanical signalling regulates instructive cues for transitions but its role in the process is uncertain. One of the primary reasons these important aspects of cell fate choice remain a mystery is because the biology has not been coupled to the biotechnology appropriate to unravel it. This is the purpose of the proposed research: we will develop tools based in microfluidics, microfabrication and hydrogels and integrate them with our stem cell biology expertise to illuminate the process of cell fate choice. We will develop single cell microfluidic technology that possesses unprecedented temporal resolution and control over the signalling environment to study cell fate dynamics. We will also synthesize hydrogel substrates to exert complete control over the mechanical microenvironment of stem cells. Finally, we will advance tools to apply reproducible and defined forces to cells in order to study the role mechanical signalling in cell fate choice. Developing the proposed technology kit hand-in-hand with its biological applications will allow us to delve into the mechanisms of biological transitions in multiple stem cell systems, allowing us to uncover universal phenomena governing cell fate choice.

Mots-clés : biophysics,mechanical signalling,cell fate,cellular transitions
Projet ERC : CRADLE (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1709375.0 €

The evolution in drug regulation of the last 50 years has left pregnant women and their fetuses orphaned. This is particularly problematic for cancer during pregnancy, which raises a difficult and conflicting medical ethical decision process and which has recently become increasingly frequent. In 2012 we published the first prospective study indicating that antenatal exposure to cancer treatment can overall be considered safe. Building on this proof of concept, the current proposal wants to take a groundbreaking step towards developing a standard of care for cancer during pregnancy by addressing –in an integrated fashion- the challenges at the level of the fetus, the mother and the fetomaternal barrier. At the core of this proposal lies an international registry of pregnant women with cancer, along with a registry of their children, and biobanks of maternal, placental, cord blood and tumoral tissues. Research track ‘child’ aims to deliver robust evidence of fetal safety. Research track ‘mother’ aims to address the emerging concerns in the oncological management of the mother, and specifically, the possible distinct biology of pregnancy-associated breast cancer, the most frequent cancer type in pregnancy. The research approach includes large-scale clinical follow-up studies along with laboratory studies on patient biomaterials, including pharmacological investigations and RNA-sequencing studies. Complementary to these studies is research track ‘placenta’ in which cutting-edge models of human placental research are used to address the poorly understood physiological basis of the placental barrier function in this specific situation. This ambitious program will rely on a multidisciplinary team of experts. Not only may the scientific deliverables of this proposal constitute a major step forward to the well-being of both mother and fetus in a pregnancy complicated by cancer, the methodological approach may also provide critical impetus to further research in this field.

Mots-clés : cancer,chemotherapy,pregnancy,pediatric
Projet ERC : MultiLevelLandscape (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
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 : 2000000.0 €

The evolution of specificity between interacting biological molecules underlies the diversification and expansion of biological pathways. A shift in specificity poses a serious theoretical problem; it requires coordinated mutations in the interacting partners, but mutation in one partner may lead to loss of interaction and functional failure. While some theoretical suggestions were proposed to solve this 'specificity valley crossing' problem, it remains a challenge to study this problem empirically at the molecular level. In bacteria, there are numerous divergent evolving pathways. Many of these pathways are involved in mediating conflicts between selfish genes, cells and populations. We and others have speculated that such multilevel selection can facilitate pathway divergence. Here we propose to study this link using the Rap-Phr cell-cell communication system, which has diversified to ~100 specific systems in the B. subtilis lineage. These systems consist of a receptor (Rap) and its cognate peptide pheromone (Phr) that influence multiple levels of selection. They promote their own horizontal transfer, modulate core cellular pathways, and manipulate cooperation between cells. Combining modelling with deep mutational scanning, competition assays and time-lapse microscopy we will quantitatively study all these levels of selection and their implication for diversification on a large fitness landscape. Specifically, we will (1) map the Rap-Phr interaction landscape at unprecedented resolution, constructing and screening libraries of ~106 Phr peptide variants and ~104 Rap variants. (2) Quantify the fitness effects of these systems at multiple levels of selection in biofilms. (3) Theoretically generate and experimentally verify predictions about how Rap-Phr co-evolve and diversify. Our work will pioneer the study of fitness landscapes under multilevel selection and provide a direct, quantitative, and predictive framework for understanding the evolution of specificity.

Mots-clés : multi level selection,social evolution,fitness landscapes,diversification,microbial systems biology,microbial development,biofilms,quorum sensing,mobile genetic elements,protein interactions
Projet ERC : Daphne (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 1446542.0 €

The evolutionary arms race has optimized and shaped the way animals attend to relevant sensory stimuli in an ever-changing environment. This is a complex task, because the vast majority of sensory experiences are not relevant. In humans, attentional disorders are a serious public health concern because of its high prevalence, but its causes are mostly unknown. In this proposal, I will explore the neuronal mechanisms used by the nervous system to attend visual cues to enable appropriate behaviors. We will combine cutting edge imaging techniques, optogenetic interventions, behavioral read outs and targeted connectomics to study the neuronal transformations of the mouse Superior Colliculus (SC), an evolutionary conserved midbrain area known to process sensorimotor transformations and to be involved in the allocation of attention. First, this work will reveal a detailed description of visual representation in the SC, focusing on understanding how defined retinal information-streams, like motion and color, contribute to these properties. Second, we will characterize sensorimotor transformations instructed by the SC. The combination of the previous two objectives will determine mechanisms of visual saliency and sensory driven attention (“bottom-up” attention). Finally, we will explore the neuronal mechanisms of attention by studying the modulatory effect of higher brain areas (“top-down” attention) on sensory transformation and multisensory integration in the SC. Taken together, this proposal aims to understand principles underlying sensorimotor transformation and build a framework to study attention in health and disease.

Mots-clés : visual system,sensory transformations,sensorimotor integration
Projet ERC : DECODE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Heidelberg University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2812500.0 €

The evolutionary success of multicellular organisms is based on the division of labor between cells. While some of the molecular determinants for cell fate specification have been identified, a fundamental understanding of which genetic activities are required in each cell of a developing tissue is still outstanding. The DECODE project will develop and apply leading-edge system genetics methods to Arabidopsis and Drosophila, two major model systems from the plant and animal kingdoms to decode context-dependent genetic networks in vivo. To achieve this, DECODE will bring together experimental and theoretical groups with complementary expertise in model organism genetics and cellular phenotyping, single-cell genomics, statistics and computational biology. Building on our combined expertise, we will create functional genetic maps using conditional CRISPR/Cas9-based single- and higher order knockout perturbations in vivo combined with single-cell expression profiling and imaging. Coupled with powerful computational analysis, this project will not only define, predict and rigorously test the unique genetic repertoire of each cell, but also unravel how genetic networks adapt their topology and function across cell types and external stimuli. With more than thousand conditional knockouts, characterized by several million single-cell transcriptome profiles and high-resolution imaging this project will create the largest single-cell perturbation map in any model organism and will provide fundamental insights into the genetic architecture of complex tissues. Analyzing two tissues with divergent organization and regulatory repertoire will enable us to uncover general principles in the genetic circuits controlling context dependent cell behavior. Consequently, we expect that the DECODE project in model organisms will lay the conceptual and methodological foundation for perturbation-based functional atlases in other tissues or species.

Mots-clés : systems genetics,single cell transcriptomics,genetic networks,cell identity,cell states
Projet ERC : DECODE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : German Cancer Research Center — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : DKFZ
Type d'entité : Recherche
Financement ERC de l'entité : 4042500.0 €

The evolutionary success of multicellular organisms is based on the division of labor between cells. While some of the molecular determinants for cell fate specification have been identified, a fundamental understanding of which genetic activities are required in each cell of a developing tissue is still outstanding. The DECODE project will develop and apply leading-edge system genetics methods to Arabidopsis and Drosophila, two major model systems from the plant and animal kingdoms to decode context-dependent genetic networks in vivo. To achieve this, DECODE will bring together experimental and theoretical groups with complementary expertise in model organism genetics and cellular phenotyping, single-cell genomics, statistics and computational biology. Building on our combined expertise, we will create functional genetic maps using conditional CRISPR/Cas9-based single- and higher order knockout perturbations in vivo combined with single-cell expression profiling and imaging. Coupled with powerful computational analysis, this project will not only define, predict and rigorously test the unique genetic repertoire of each cell, but also unravel how genetic networks adapt their topology and function across cell types and external stimuli. With more than thousand conditional knockouts, characterized by several million single-cell transcriptome profiles and high-resolution imaging this project will create the largest single-cell perturbation map in any model organism and will provide fundamental insights into the genetic architecture of complex tissues. Analyzing two tissues with divergent organization and regulatory repertoire will enable us to uncover general principles in the genetic circuits controlling context dependent cell behavior. Consequently, we expect that the DECODE project in model organisms will lay the conceptual and methodological foundation for perturbation-based functional atlases in other tissues or species.

Mots-clés : systems genetics,single cell transcriptomics,genetic networks,cell identity,cell states
Projet ERC : DECODE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 3770000.0 €

The evolutionary success of multicellular organisms is based on the division of labor between cells. While some of the molecular determinants for cell fate specification have been identified, a fundamental understanding of which genetic activities are required in each cell of a developing tissue is still outstanding. The DECODE project will develop and apply leading-edge system genetics methods to Arabidopsis and Drosophila, two major model systems from the plant and animal kingdoms to decode context-dependent genetic networks in vivo. To achieve this, DECODE will bring together experimental and theoretical groups with complementary expertise in model organism genetics and cellular phenotyping, single-cell genomics, statistics and computational biology. Building on our combined expertise, we will create functional genetic maps using conditional CRISPR/Cas9-based single- and higher order knockout perturbations in vivo combined with single-cell expression profiling and imaging. Coupled with powerful computational analysis, this project will not only define, predict and rigorously test the unique genetic repertoire of each cell, but also unravel how genetic networks adapt their topology and function across cell types and external stimuli. With more than thousand conditional knockouts, characterized by several million single-cell transcriptome profiles and high-resolution imaging this project will create the largest single-cell perturbation map in any model organism and will provide fundamental insights into the genetic architecture of complex tissues. Analyzing two tissues with divergent organization and regulatory repertoire will enable us to uncover general principles in the genetic circuits controlling context dependent cell behavior. Consequently, we expect that the DECODE project in model organisms will lay the conceptual and methodological foundation for perturbation-based functional atlases in other tissues or species.

Mots-clés : systems genetics,single cell transcriptomics,genetic networks,cell identity,cell states
Projet ERC : ECOLBEH (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 419381.0 €

The evolutionary transition from solitary to group living has fundamentally changed how organisms interact with their environment. However, to reap the rewards of group living, from collective intelligence to predator avoidance, group members must maintain cohesion by making collective decisions. Theory suggests that individuals’ ability to influence collective decisions could be determined by a range of factors, including their state, social role, relationships with other group members, the composition of their social group, and the physical environment. Although these factors could all interact, most empirical studies have investigated them in isolation. The aim of this project is to take a ‘whole-system’ approach by quantifying (1) how individual-level factors determine leadership, (2) how movement decisions are modulated by long-term social and genetic relationships among group members, and (3) whether the mechanisms by which groups reach consensus are resilient to rapid environmental change. This research program will add unprecedented ecological validity and replication to the field of collective decision making. I will leverage state-of-the-art technology and develop novel methods to simultaneously collect and analyse multi-scale data in a wild population of highly social birds. These data include the movement of individuals within and between groups (high-resolution GPS), social interactions (direct observations), kinship (whole-genome sequencing), physiology (heart rate), and environmental conditions (drone-based mapping). The analytical methods I will develop (e.g. multi-layered dynamic social network analysis) will provide new tools for the research community, while integrating these unique data across replicated groups and over multiple generations, the project will bring new depth to the field. This depth is essential to address the questions that are central to our understanding of social behaviour in mobile animal groups, including humans.

Mots-clés : social behaviour,collective decision making,social network analysis,animal behaviour,movement,ecological conditions
Projet ERC : NEDM (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 89043.75 €

The existence of a permanent electric dipole moment (EDM) of the neutron, or any subatomic particle, would have far reaching implications connecting particle physics with cosmology. Time reversal invariance and CP symmetry would be violated. A new fundamental interaction producing the EDM, that is, deforming the charge distribution inside the neutron, could also have generated the matter-antimatter asymmetry in the early Universe. After 60 years of evolution, techniques to measure the neutron EDM are now so evolved that experiments are sensitive to microphysics associated with an energy scale beyond that accessible at the LHC. This situation offers a high likelihood of discovery for the next generation of experiments. In the same time, any improvement in precision is technically challenging. The control of the magnetic field must surpass that of the state of the art of atomic magnetometers. The n2EDM project aims at improving the precision by an order of magnitude or more. Systematic effects need to be controlled at an unprecedented level. In particular, the use of a mercury co-magnetometer based on the precession of 199Hg spins induces a set of subtle false effects due to the relativistic motional field. I propose to initiate a comprehensive program to master these systematic effects beyond the current research program. In particular, the proposed project includes a precise determination of the 199Hg magnetic moment with a precision of 0.1 ppm. To this end, I will attempt a novel approach: combining mercury and 4He magnetometry in the same cell. As a by-product, this will also produce an improved determination of the neutron magnetic moment, a quantity of interest for metrology. The cross-check I propose will prove that all disturbances on the neutron or mercury spins are mastered at the sub-ppm level, a decisive step in the quest for the neutron EDM.

Mots-clés : baryogenesis