Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : LSDiASD (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Ttfactor srl — Pays : Italie — Rôle : Partner
Acronyme de l'entité : Ttf
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 37500.0 €

Duplication of chromosome region 7q11.23 (7Dup), comprising 26-28 genes, is one of best characterized copy number variations (CNV) causing Autism Spectrum Disorder (ASD), a very prevalent neurodevelopmental condition affecting more than 1% individuals worldwide, and for which no effective treatment is available. Despite the remarkable consistency of core ASD symptoms (impairment in language and sociability along with stereotyped behaviours), over 400 causative genetic lesions have been thus far identified for ASD, splitting it de facto into an aggregate of rare and highly penetrant genetic diseases. In turn, the convergence of symptoms grounds the hope that few paradigmatic syndromes may yield generalizable therapeutic inroads across the autistic spectrum. 7Dup is a case in point since it is symmetrically opposite to Williams Syndrome, a condition caused by 7q11.23 hemideletion and featuring symmetrically opposite phenotypes in language and sociability, thus offering unique opportunities to dissect the dosage-vulnerable circuits that affect language competence and sociability. Specifically, convergent evidence points to transcription factor GTF2I as the key gene underlying the cognitive/behavioural traits of 7Dup. Within my ERC-Consolidator project DISEASEAVATARS we discovered that increased GTF2I dosage represses key genes involved in intellectual disability, autism and neuronal function by associating with lysine demethylase 1 (LSD1), a key chromatin modifier, and found that LSD1 inhibition rescues GTF2I-dependent alterations. Therefore, we now wish to establish in vivo proof of concept for the efficacy of novel LSD1 inhibitors in rescuing cognitive-behavioural deficits in relevant ASD mouse models recapitulating GTF2I CNV, developing an adequate business plan and industrial partnerships as prerequisites for advancing the most effective LSD1 inhibitor towards pre-clinical development for 7Dup and ASD more broadly.

Mots-clés : autism,demethylase inhibitors,sociability,7q11 23 duplication,gtf2i
Projet ERC : EpiCrest2Reg (Horizon 2020, appel 2018, Synergy grants)
Entité participante : University Hospital of Basel — Pays : Suisse — Rôle : Partner
Acronyme de l'entité : USB
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 2653750.0 €

During craniofacial development, Cranial Neural Crest Cells (CNCCs) maintain broad plasticity and patterning competence until they make appropriate cartilage and bone structures in response to local cues. We found that CNCC embryonic plasticity involves a specific epigenetic chromatin signature that maintains genes, including Hox genes, in a transcriptionally silent but poised state, so that they can be readily switched to an active state in response to position-specific environmental signals. Are there CNCC-derived subpopulations in the adult face cartilage with similar broad plasticity properties that could be used as progenitor source in regenerative medicine? We have shown that Hox-negative adult human CNCC-derived Nasal Chondrocytes (NCs) have cartilage regenerative capacity and plasticity to adapt to heterotopic sites larger than other cell sources, and demonstrated their potential clinical use for articular cartilage repair. However, lack of understanding of the involved molecular mechanisms limits the broader utilization of adult NCs for the regeneration of other cartilage types, e.g. the intervertebral disc (IVD). This proposal will establish fundamental understanding of the biological processes responsible for the plasticity of adult human NCs and offer a paradigm example of scientific and clinical synergies bridging developmental (epi)genetics and regenerative medicine. We will: • Establish whether Hox-negative adult NCs and embryonic CNCCs share similar transcriptomes, epigenomes and 3D chromatin architectures using single cell RNA-seq, ChIP-seq and capture HiC-seq assays. • Assess whether NCs can epigenetically and transcriptionally adapt to the Hox-positive IVD environment, using co-culture and bioreactor-based organ culture models, and investigate the underlying molecular mechanisms. • Verify the capacity of adult NCs to repair degenerated IVD cartilage. • Use human autologous NCs for repair of IVD degeneration in a phase I clinical trial.

Mots-clés : cranial neural crest cells,epigenetic and transcriptional regulation,craniofacial development,nasal chondroprogenitor cells,mouse,cartilage regeneration in humans,hox genes
Projet ERC : SPACEVAR (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Max Delbrück Center for Molecular Medicine — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MDC
Type d'entité : Recherche
Financement ERC de l'entité : 1499883.0 €

During embryonic development a single cell turns into a complex organism. This process is characterized by an antagonism between variation and stability. On the one hand, development is a tightly controlled process; tissues need to be specified at the right time, at the correct spatial position, and with a defined size. On the other hand, regulation should not be too rigid, since embryos need to adjust to environmental perturbations and correct errors caused by noisy gene expression. We will study variation and stability during pattern formation in the zebrafish heart. We seek to understand the origin of embryo-to-embryo variability as well as robustness against perturbation. The zebrafish heart is a powerful model system for studying variability, since heart positioning is inverted along the left/right axis in 5-10% of wildtype embryos. We aim to identify the mechanism underlying variability in heart positioning and understand its function. To this end, we will combine two innovative approaches: Tomo-seq, a novel method for spatially-resolved transcriptomics developed by the applicant; and single-molecule FISH, a technique that allows absolute quantification of gene expression in single cells. To expand our study of embryo-to-embryo variability beyond gene expression analysis, we will optimize a method for massively parallel single-cell lineage tracing based on CRISPR-Cas. This novel approach will allow us to study embryo-to-embryo variability in developmental lineage specification on the single cell level. We will use this strategy to systematically explore the corrective capacity of the zebrafish heart upon perturbation of progenitor cell pools, and to determine which mechanisms for error correction are activated in the embryo. These quantitative experiments will provide unprecedented insight into variability and robustness during development. The concepts developed here will also be relevant for improving our understanding of variable outcomes in human disease.

Mots-clés : zebrafish,heart development,quantitative developmental biology,variability and robustness,single cell biology
Projet ERC : SymPore (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2471500.0 €

During evolution of multicellularity, cells differentiated to become specialized and interdependent. Multicellular organisms invented channels for nutrient exchange and communication between cells. Plants uniquely developed plasmodesmata, complex cell-cell connections traversing the cell wall. Roles ascribed to plasmodesmata include selective transport of signals, ions, metabolites, RNAs and proteins. Due to technical hurdles, composition, structure and regulation of plasmodesmatal conductance remain enigmatic. Genetic approaches to study plasmodesmata were hampered by lethality or redundancy. Novel technologies now set the stage for resolving roles of plasmodesmata in transport and signaling in an interdisciplinary approach. We will use proximity labeling proteomics to obtain plasmodesmatal composition, and PAINT and cryo electron tomography (cryoET) for near atomic structures. Models of plasmodesmata will be built from bottom up and top down approaches and combined with quantitative assessment of plasmodesmatal activity. Novel biosensor approaches together with knock down by genome editing will permit quantitation of transport of the diverse cargo. Single cell sequencing helps fine-tuning mutant selection and targeting of subtypes. Four labs will join forces: highly recognized experts in biophysics and cryoET (WB), advanced imaging and developmental signaling (RS), high-end proteomics and lipidomics (WS), and interactomics, transporters and cutting-edge biosensor technology (WF). We will iteratively address: (1) systematic quantitative identification of components, (2) their localization and dynamics, (3) structures and molecular building blocks of diverse plasmodesmatal types, and (4) transport and signaling mechanisms. We expect breakthrough discoveries and completely new understanding of plasmodesmatal function and evolution. Since plasmodesmata play key roles in nutrient allocation and virus spread, we lay the basis for novel biotech solutions in agriculture.

Mots-clés : cryo electron tomography,protein interactions,imaging,microscopy,mass spectrometry,transport,modeling,biosensors,plant,moss,arabidopsis,plasmodesmata,genome editing,signaling,cytoplasmic bridges,pit plugs,development,physiology,evolution
Projet ERC : SHUFFLE (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : James Hutton Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2499980.0 €

During meiosis, recombination (crossing-over, CO) drives the exchange of genetic materials and releases genetic diversity by creating new combinations of alleles within and among chromosomes. CO is exploited in plant breeding through the generation of large populations of recombinants from which genetically improved individuals are selected. However in some economically important crops such as barley, the rate of improvement has plateaued. One hypothesis is that this is due to constraints on the locations of CO. In large genome cereals CO is restricted to the ends of chromosomes, excluding approximately two thirds of the genome from the breeding process. This project focuses on three critically important questions about CO in barley: Why is it restricted to the telomeric ends of chromosomes? What proteins are the key players and what are their roles in controlling CO? And, what strategies can be established to effectively increase or redistribute CO in CO-poor regions? I will address these questions in four Work Packages. In WP1 I will induce, identify and molecularly characterise putative meiotic mutants both phenotypically (at the plant level) and molecularly by captured exome sequencing. In WP2 I will characterise these mutants cytologically, genetically and by complementation to understand how the mutations affect recombination. In WPs 3 and 4, I will apply novel methods to isolate the specific cells undergoing meiosis, and use transcriptomics, targeted proteomics and pull-down assays to investigate how meiosis is regulated. I will focus on complexes that mark the sites of DNA double strand break (DSB) formation that identify where CO will occur. I will characterise these sites according to those resolved as either crossing-over or non-crossing-over events and relate their physical location to COs observed in population genetic data. Finally, I will evaluate strategies for modifying the distribution of recombination, and application in plant breeding
Projet ERC : MECHEMGUI (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Erlangen-Nuremberg — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : FAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

During the development of the central nervous system (CNS), neurons extend axons through a crowded environment along well-defined pathways to reach their distant targets. It isA start date of 1st June 2018 is being requested to enable the PI to complete a number of current commitments and put the necessary arrangements in place to enable an efficient start up phase of the project. evident that attractive and repulsive guidance cues in the tissue provide important biochemical signals to guide growing axons along their paths. This can only be part of the story, however, as it is still not possible to predict axonal growth patterns in vivo. In a recent breakthrough discovery, we provided in vivo evidence that neurons also respond to mechanical cues, such as local tissue stiffness, suggesting that mechanical signals are likely an important missing part of the puzzle. However, mechanically activated signaling pathways are currently poorly understood, and how neurons integrate mechanical and chemical signals to result in proper outgrowth is unknown. By investigating how mechanical signals control neuronal growth and pathfinding, this proposal will close this comprehension gap. By combining state-of-the-art approaches in physics, engineering and biology, we will, for the first time, identify mechanosensitive molecular mechanisms that regulate neuronal growth and guidance in vitro and in vivo. In particular, we will investigate how mechanotransduction cascades (1) directly modulate axon growth by inducing local changes in cytoskeletal dynamics, and (2) indirectly lead to alterations in axon outgrowth by modulating chemical signalling pathways. Ultimately, we will develop a computational model based on our findings, which will lead to a predictive framework for understanding axon pathfinding in the developing brain. The proposed research challenges current concepts in developmental biology and is very relevant to many other areas in biology. Our results will not only shed new light on the complex control mechanisms of cellular growth and motility, but could also lead to novel biomedical approaches aimed at facilitating neuronal re-growth and regeneration in the damaged CNS.

Mots-clés : mechanobiology,biophysics,mechanotransduction,forces,tissue stiffness,atomic force microscopy,traction force microscopy
Projet ERC : MECHABLASTO (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Institut Curie — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 306083.5 €

During the first days of mammalian development, blastomeres organize themselves into the blastocyst, which implants the embryo into the maternal uterus. Failure to build the blastocyst will result in a miscarriage and yet the mechanisms underlying the construction of the blastocyst are mostly unknown. The blastocyst is sculpted by forces generated by its constituent cells. Without a tool to study the mechanics of the mammalian embryo, it is challenging to identify the molecules and cellular processes controlling morphogenetic forces. Using biophysical methods, I have recently measured the forces shaping the mouse blastocyst and identified cellular processes generating and controlling them. This approach enables the identification of the molecules controlling morphogenesis and constitutes the first step towards a complete theoretical modelling of blastocyst morphogenesis. The aim of this project is to understand the molecular and mechanical aspects of blastocyst morphogenesis. By developing novel biophysical tools for the developing blastocyst, we will measure uncharacterized mechanical properties such as cytoplasmic and luminal pressure, adhesion strength and viscosity. The resulting mechanical map of the blastocyst will help understand the mechanisms of action of genes involved in its morphogenesis. To identify novel candidate genes involved in blastocyst morphogenesis, we will carry out a screen using live high-resolution confocal microscopy of mouse embryos injected with siRNA. Together, this will reveal the molecular, cellular and mechanical processes controlling blastocyst morphogenesis. I expect this to shed light on how blastomeres self-organize into the blastocyst and to reveal the physical laws underlying morphogenesis in general. Importantly, the knowledge and non-invasive biophysical techniques that we will develop will help developing Assisted Reproduction Technologies, which will be greatly beneficial to the fertility of the ageing European population.
Projet ERC : BigEarth (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : University of Trento — Pays : Italie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

During the last decade, a huge number of earth observation (EO) satellites with optical and Synthetic Aperture Radar sensors onboard have been launched and advances in satellite systems have increased the amount, variety and spatial/spectral resolution of EO data. This has led to massive EO data archives with huge amount of remote sensing (RS) images, from which mining and retrieving useful information are challenging. In view of that, content based image retrieval (CBIR) has attracted great attention in the RS community. However, existing RS CBIR systems have limitations on: i) characterization of high-level semantic content and spectral information present in RS images, and ii) large-scale RS CBIR problems since their search mechanism is time-demanding and not scalable in operational applications. The BigEarth project aims to develop highly innovative feature extraction and content based retrieval methods and tools for RS images, which can significantly improve the state-of-the-art both in the theory and in the tools currently available. To this end, very important scientific and practical problems will be addressed by focusing on the main challenges of Big EO data on RS image characterization, indexing and search from massive archives. In particular, novel methods and tools will be developed, aiming to: 1) characterize and exploit high level semantic content and spectral information present in RS images; 2) extract features directly from the compressed RS images; 3) achieve accurate and scalable RS image indexing and retrieval; and 4) integrate feature representations of different RS image sources into a unified form of feature representation. Moreover, a benchmark archive with high amount of multi-source RS images will be constructed. From an application point of view, the developed methodologies and tools will have a significant impact on many EO data applications, such as accurate and scalable retrieval of: specific man-made structures and burned forest areas.
Projet ERC : SOLID (Horizon 2020, appel 2018, Synergy grants)
Entité participante : European University Institute — Pays : Italie — Rôle : PI
Acronyme de l'entité : EUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3341367.5 €

During the post 2008 decennium horribile the EU has been faced with unprecedented shocks (the Euro-crisis, the Great Recession and its dramatic social consequences, new security threats, the refugee crisis, Brexit) which have coalesced in a disruptive dynamic of unprecedented scope and depth. Conflicts over sovereignty, solidarity and identity sparked a “deep” political crisis, shaking the very foundations of the EU. Surprisingly, however, the utter collapse of the Union has been averted. In dramatic moments EU leaders agreed on significant institutional advances or at least some backstops. How can one explain this peculiar mix of crisis and resilience? The SOLID project posits that sequences of policy crises tend to disrupt routine policy-making, jeopardize its responsiveness, unleash turbulent forms of crisis politics, and put political legitimacy (even polity durability) at risk. At the same time we also posit that severe crisis situation may also activate polity maintenance incentives for keeping the political community together “whatever it takes”. Covering developments since 2009, SOLID ultimately aims at assessing the overall soundness of the EU’s foundations in the wake of the political crisis. In order to capture both disruption and resilience, we propose to disentangle the “deep” political dimension of the crisis from more policy-specific challenges and analyze it through a “coalition-centered approach”, which we have originally devised for the EU polity. Rooted in political economy, comparative political sociology and policy analysis, SOLID will collect extensive data on processes, conflicts and coalitions through qualitative and quantitative methods, including innovative techniques. A major original survey will also be organized. We aim at providing an original general theory of political crisis, valuable as such, but making a strong impact on the study of EU politicization and its likely (constructive or destructive) outcomes.

Mots-clés : european integration,sovereignty,identity,solidarity,social and political crisis,social and political coalitions,economic and social policy making,territorial politics,elections,parties
Projet ERC : EpiTALL (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 958750.0 €

Dynamic interplay between histone modifications and DNA methylation defines the chromatin structure of the humane genome and serves as a conceptual framework to understand transcriptional regulation in normal development and human disease. The ultimate goal of this research proposal is to study the chromatin architecture during normal and malignant T cell differentiation in order to define how DNA methylation drives oncogenic gene expression as a novel concept in cancer research. T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric and 25% of adult ALL cases and was originally identified as a highly aggressive tumor entity. T-ALL therapy has been intensified leading to gradual improvements in survival. However, 20% of pediatric and 50% of adult T-ALL cases still relapse and ultimately die because of refractory disease. Research efforts have unravelled the complex genetic basis of T-ALL but failed to identify new promising targets for precision therapy. Recent studies have identified a subset of T-ALLs whose transcriptional programs resemble those of early T-cell progenitors (ETPs), myeloid precursors and hematopoietic stem cells. Importantly, these so-called ETP-ALLs are characterized by early treatment failure and an extremely poor prognosis. The unique ETP-ALL gene expression signature suggests that the epigenomic landscape in ETP-ALL is markedly different as compared to other genetic subtypes of human T-ALL. My project aims to identify genome-wide patterns of DNA methylation and histone modifications in genetic subtypes of human T-ALL as a basis for elucidating how DNA methylation drives the expression of critical oncogenes in the context of poor prognostic ETP-ALL. Given that these ETP-ALL patients completely fail current chemotherapy treatment, tackling this completely novel aspect of ETP-ALL genetics will yield new targets for therapeutic intervention in this aggressive haematological malignancy.