Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : IDRICA (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : CERCA Institution — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CERCA;I-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.

Mots-clés : arabidopsis,crops,shorgum,brassinosteorid,signaling,receptors,root,drought,hydrotropism,systematic phenotyping,agrochemicals,transcriptomics
Projet ERC : 4-D nanoSCOPE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : University of Erlangen-Nuremberg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2755050.0 €

Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function. To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo. The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.

Mots-clés : bone structure,bone disease,bone mechanics,x ray microscopy,image reconstruction,correlative microscopy,osteoporosis,arthritis,deep learning
Projet ERC : 4-D nanoSCOPE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Helmholtz-Zentrum Berlin für Materialien und Energie — Pays : Allemagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 0.0 €

Due to Europe's ageing society, there has been a dramatic increase in the occurrence of osteoporosis (OP) and related diseases. Sufferers have an impaired quality of life, and there is a considerable cost to society associated with the consequent loss of productivity and injuries. The current understanding of this disease needs to be revolutionized, but study has been hampered by a lack of means to properly characterize bone structure, remodeling dynamics and vascular activity. This project, 4D nanoSCOPE, will develop tools and techniques to permit time-resolved imaging and characterization of bone in three spatial dimensions (both in vitro and in vivo), thereby permitting monitoring of bone remodeling and revolutionizing the understanding of bone morphology and its function. To advance the field, in vivo high-resolution studies of living bone are essential, but existing techniques are not capable of this. By combining state-of-the art image processing software with innovative 'precision learning' software methods to compensate for artefacts (due e.g. to the subject breathing or twitching), and innovative X-ray microscope hardware which together will greatly speed up image acquisition (aim is a factor of 100), the project will enable in vivo X-ray microscopy studies of small animals (mice) for the first time. The time series of three-dimensional X-ray images will be complemented by correlative microscopy and spectroscopy techniques (with new software) to thoroughly characterize (serial) bone sections ex vivo. The resulting three-dimensional datasets combining structure, chemical composition, transport velocities and local strength will be used by the PIs and international collaborators to study the dynamics of bone microstructure. This will be the first time that this has been possible in living creatures, enabling an assessment of the effects on bone of age, hormones, inflammation and treatment.

Mots-clés : bone structure,bone disease,bone mechanics,x ray microscopy,image reconstruction,correlative microscopy,osteoporosis,arthritis,deep learning
Projet ERC : SMART (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Due to the many limitations of the conventional water treatment technologies, we are witnessing alarmingly high levels of micro-pollutants (MPs) such as antibiotics, pesticides, herbicides, estrogens, and pharmaceuticals, which enter our surface and groundwater ecosystems. In SMART project we propose to use novel catalytic membranes that have shown promising results in removing a variety of highly persistent organic compounds, with a removal efficiency of over 85%. Our membranes exhibit a unique ability to wirelessly generate surface charges under the influence of magnetic fields, light, and mechanical vibrations. These surface charges generate highly reactive radicals, which possess an excellent degradation tendency towards a wide range of problematic industrial pigments, pharmaceuticals, antibiotics, estrogen, pesticides, herbicides, and disinfectants. The goal of this project is to further enhance the water purification performance of our membranes by optimizing their composition, their shape and pore sizes, as well as the operational parameters, such as flow-rate and residence time. We plan to integrate these improved membranes within a portable water treatment reactor and study its performance in eliminating a variety of MPs from contaminated wastewaters. This prototype will then be used to conduct an extensive pilot-study at a Swiss hospital. Additionally, we plan to use our water purification prototype to provide demonstrations to our potential customers, and highlight the potential of our technology to remove over 85% of these problematic MPs, in a cost and energy efficient manner.

Mots-clés : water purification,redox processes,magnetoelectricity,catalysis  micropollutants
Projet ERC : SPATEMP (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Ernst Strüngmann Institute for Neuroscience — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : ESI
Type d'entité : Recherche
Financement ERC de l'entité : 1750000.0 €

During active wakefulness, cortical activity organizes itself into highly coherent patterns of gamma waves (30-80Hz). These waves are believed to be essential for cortical communication and synaptic plasticity. Their impairment is a hallmark of neurological and psychiatric disorders. Yet, it remains heavily debated what gamma waves encode, and what their precise role in information transmission is. I have recently proposed a new theory about gamma in visual cortex, building on the predictive coding theory. The predictive coding theory holds that the brain makes active top-down predictions about its own sensory inputs. By comparing these, it generates bottom-up prediction errors to drive learning and the updating of priors. The standard view in predictive coding theories is that gamma waves carry prediction errors. However, I recently hypothesized the opposite: 1) Gamma waves signal a match between predictions and sensory inputs (i.e. predictability), and 2) Columns that predict each other's visual input engage in long-range gamma-synchronization. To test this hypothesis, it is critical to develop a new method to quantify predictions and prediction errors in the context of natural vision. I will solve this by using recently developed deep-learning networks for prediction. By making multi-areal recordings from visual cortex in marmosets and humans (MEG), I will test if predictability indeed determines gamma waves and their synchronization pattern across space. Because stimulus priors have to be acquired through learning, I will further determine whether gamma waves depend on experience and perceptual learning. In marmosets, I will develop an optogenetics approach to test whether gamma waves drive perceptual learning, and test the prediction that V1 gamma waves depend on top-down feedback. In sum, I expect to provide evidence for a new, unified theory about the role of gamma waves in information transmission and the integration of sensory evidence with predictions.

Mots-clés : predictive coding,vision,visual cortex,electrophysiology,perceptual learning,gamma oscillations,synchronization,deep learning,marmoset,optogenetics
Projet ERC : EpiCrest2Reg (Horizon 2020, appel 2018, Synergy grants)
Entité participante : University of Basel — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 6250.0 €

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 : EpiRIME (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1997500.0 €

During gametogenesis, germ cells undergo profound chromatin reorganisation, condensation and transcriptional shutdown. Upon fertilization, gamete chromatin is epigenetically reprogrammed, generating a totipotent zygote that can give rise to all cell types of the adult organism. The maternal factors that reprogram gametes to totipotency are unknown. The current dogma suggests that the parental epigenetic information must be erased in order to establish totipotency. In contrast, we have recently discovered that maternal gametes transmit the epigenetic H3K27me3 histone modification to the next generation (Zenk et al., Science, 2017) adding to increasing evidence suggesting that gametes convey more than just DNA to the offspring. Nevertheless, the underlying mechanisms and the impact of epigenetic inheritance through the gametes are not yet fully resolved. Critically, the mechanisms and impact of (i) paternal gamete reprogramming, (ii) paternal epigenetic inheritance and (iii) de novo establishment of the zygotic epigenome remain essentially unknown. The objective of this proposal is to unravel the fundamental principles underlying these three major epigenetic transitions in vivo in Drosophila. We will achieve our objective via three aims: (i) We will investigate the mechanisms underlying the reprogramming of sperm chromatin at fertilization. Specifically, we will determine the nature and extent of the contributions of two proteins essential for sperm chromatin reprogramming (ii) We will examine the mechanism of histone H3K27me3 inheritance through the paternal germline (iii) We will genetically dissect the de novo establishment of constitutive heterochromatin in the newly formed zygote. Our investigations of these epigenetic transitions are expected to reveal novel insights into the first steps in the formation of life, and to ultimately advance reproductive and regenerative medicine.

Mots-clés : germline,epigenetic inheritance,epigenetic reprogramming,drosophila early embryo development,polycomb
Projet ERC : IDRE (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Dundee — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1444081.0 €

During lineage propagation, cells must duplicate their genetic and epigenetic information to maintain cell identity. However, the mechanisms underlying the maintenance of epigenetic information in dividing cells remain largely unknown. In S phase, progression of DNA replication forks provokes a genome-wide disruption of the epigenetic information. While nucleosomes are rapidly reassembled on newly replicated DNA, full restoration of epigenetic information is not completed until after mitosis. This proposal aims to reveal how cells restore epigenetic information after DNA replication. To address this question, I have developed a new technology called Nascent Chromatin Capture (NCC). NCC is a powerful and versatile method that allows purification and analysis over time of proteins associated with replicated DNA. (1) I will identify novel mechanisms in chromatin restoration in mother and daughter cells. To this end I will combine NCC with quantitative mass spectrometry, high-throughput microscopy and screening technologies. Furthermore, I will develop original strategies to directly study the impact of chromatin restoration defects on genome integrity and differentiation potential. (2) It remains unknown whether specific loci as DNA replication origins, have a particular mode of restoration. I propose to develop a new technology, NCC-Ori, to capture chromatin at DNA replication origins. This innovative cutting edge technology will permit to unravel molecular mechanisms that underpin chromatin restoration at these specific sites and uncover chromatin determinants of replication timing and origin activation. (3) Newly identified players that are linked to human diseases will be characterized in order to understand their role in disease etiology and their therapeutic potential. Altogether, these integrated approaches should provide new insights into the molecular mechanisms that coordinate genome and epigenome maintenance across cell generations.
Projet ERC : XPRESS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 477468.69 €

During mammalian development, precise gene expression patterns have to be established and then maintained, or reversed, in different cellular and tissue contexts. A striking example of such developmentally regulated gene control is X-chromosome inactivation (XCI), whereby one of the two X chromosomes in females is silenced during embryogenesis. XCI is initiated by the non-coding Xist RNA, which coats the chromosome in cis, triggering gene repression, chromatin changes and chromosomal reorganisation. Although Xist’s regulation has been investigated intensively, less is known about the actual mechanisms underlying the process of chromosome-wide gene silencing that it induces. Indeed, X-linked loci show very different kinetics of repression during development, implying regional and/or locus specific diversity. Furthermore, some genes avoid or escape XCI altogether, either constitutively or in a tissue or stage-specific fashion, but the molecular basis for this is unclear. Here we propose to dissect the mechanisms underlying gene regulation during XCI. We will investigate the roles of recently identified Xist partners in gene silencing and perform genetic screens to identify new factors involved in silencing and escape from XCI. Transcription, chromatin status and chromosome conformation during XCI will be investigated in an allelic-specific manner during precise developmental time windows to pinpoint the critical changes accompanying silencing and escape. We will use genetic engineering to alter genomic and epigenomic landscapes of selected loci and target candidate trans-acting factors to their putative regulatory elements. Finally, we will develop tools to explore gene expression during XCI using live cell imaging of embryogenesis. Using this innovative set of approaches, we hope to define both general principles underlying gene silencing and escape in XCI, as well as locus-specific features that could serve as new paradigms for research in developmental epigenetics.

Mots-clés : x inactivation,epigenetics,gene regulation
Projet ERC : XPRESS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Institut Curie — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 1572044.13 €

During mammalian development, precise gene expression patterns have to be established and then maintained, or reversed, in different cellular and tissue contexts. A striking example of such developmentally regulated gene control is X-chromosome inactivation (XCI), whereby one of the two X chromosomes in females is silenced during embryogenesis. XCI is initiated by the non-coding Xist RNA, which coats the chromosome in cis, triggering gene repression, chromatin changes and chromosomal reorganisation. Although Xist’s regulation has been investigated intensively, less is known about the actual mechanisms underlying the process of chromosome-wide gene silencing that it induces. Indeed, X-linked loci show very different kinetics of repression during development, implying regional and/or locus specific diversity. Furthermore, some genes avoid or escape XCI altogether, either constitutively or in a tissue or stage-specific fashion, but the molecular basis for this is unclear. Here we propose to dissect the mechanisms underlying gene regulation during XCI. We will investigate the roles of recently identified Xist partners in gene silencing and perform genetic screens to identify new factors involved in silencing and escape from XCI. Transcription, chromatin status and chromosome conformation during XCI will be investigated in an allelic-specific manner during precise developmental time windows to pinpoint the critical changes accompanying silencing and escape. We will use genetic engineering to alter genomic and epigenomic landscapes of selected loci and target candidate trans-acting factors to their putative regulatory elements. Finally, we will develop tools to explore gene expression during XCI using live cell imaging of embryogenesis. Using this innovative set of approaches, we hope to define both general principles underlying gene silencing and escape in XCI, as well as locus-specific features that could serve as new paradigms for research in developmental epigenetics.

Mots-clés : x inactivation,epigenetics,gene regulation