Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CORONALDOLLS (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of St Andrews — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

CORONALDOLLS will tackle the long-standing question of the extremely high temperatures in the Sun’s outer atmosphere (corona) by taking a modern, progressive approach: forward modelling (creating synthetic observations) will be used to (i) link 3D numerical simulations of in-depth models with large scale computational experiments and (ii) provide observational diagnostics to compare models to high resolution, multi wavelength observations both qualitatively and quantitatively. This timely, multi-scale (‘russian dolls’) approach will achieve an innovative synergy between coronal heating and coronal seismology, where the coronal heating models will use input from, and be benchmarked against, information gained about the solar atmosphere through coronal seismology. From a series of in-depth, 3D numerical studies, considering, in turn, three of the most promising heating processes (Taylor relaxation, braiding and Alfvén wave heating) at their particular spatial and temporal scales, we will determine: - the cadence of the heating: low-frequency (‘bursty’) vs high-frequency (‘near-continuous’); - the range of parameters for which heating is most efficient (i.e. reaches a threshold temperature and is distributed throughout the 3D volume); - observational diagnostics to compare with large scale computational experiments and observational data. This systematic, comprehensive study will allow CORONALDOLLS to answer the fundamental question: Can we unambiguously identify physical heating mechanisms and determine their relative contributions, both in large-scale numerical simulations and high resolution observations and, if so, how? In parallel, the advanced 3D computational models will provide a ‘proof of concept’ for coronal seismology, i.e. establish the robustness of the currently used simple models and how the interpretation of observed waves and oscillations in the optically thin solar atmosphere is affected by line-of-sight integration and instrument resolution.

Mots-clés : corona,coronal heating,coronal seismology,magnetic fields,numerical modelling,observational data analysis
Projet ERC : CRISPAIR (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1499763.0 €

CRISPR-Cas loci are the adaptive immune system of archaea and bacteria. They can capture pieces of invading DNA and use this information to degrade target DNA through the action of RNA-guided nucleases. The consequences of DNA cleavage by Cas nucleases, i.e. how breaks are processed and whether they can be repaired, remains to be investigated. A better understanding of the interplay between DNA repair and CRISPR-Cas is critical both to shed light on the evolution and biology of these fascinating systems and for the development of biotechnological tools based on Cas nucleases. CRISPR systems have indeed become a popular tool to edit Eukaryotic genomes. The strategies employed take advantage of different DNA repair pathways to introduce mutations upon DNA cleavage. In bacteria however, the introduction of breaks by Cas nucleases in the chromosome has been described to kill the cell. Preliminary data indicates that this might not always be the case and that some DNA repair pathways could compete with CRISPR immunity allowing cells to survive. Using a combination of bioinformatics and genetics approaches we will investigate the interplay between CRISPR and DNA repair in bacteria with a particular focus on the widely used CRISPR-Cas9 system. The knowledge gained from this study will then help us develop novel tools for bacterial genome engineering. In particular we will introduce a NHEJ pathway in E.coli making it possible to perform CRISPR knockout screens. Finally using CRISPR libraries and multiplexed targeting, we will generate for the first time all combinations of pair-wise gene knockouts in an organism, a task that for now remains elusive, even for large consortiums and with the use of automation. This will enable to decipher genome-scale genetic interaction networks, an important step for our understanding of bacteria as a system.

Mots-clés : crispr,phage,genome editing,genetic interaction,gene regulation,dna repair
Projet ERC : CRISPR-EVOL (Horizon 2020, appel 2017, Advanced 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 : 2495625.0 €

CRISPR-Cas systems are microbial defense systems that provide prokaryotes with acquired and heritable DNA-based immunity against selfish genetic elements, primarily viruses. However, the full scope of benefits that these systems can provide, as well as their costs remain unknown. Specifically, it is unclear whether the benefits against viral infection outweigh the continual costs incurred even in the absence of parasitic elements, and whether CRISPR-Cas systems affect microbial genome diversity in nature. Since CRISPR-Cas systems can impede lateral gene transfer, it is often assumed that they reduce genetic diversity. Conversely, our recent results suggest the exact opposite: that these systems generate a high level of genomic diversity within populations. We have recently combined genomics of environmental strains and experimental genetics to show that archaea frequently acquire CRISPR immune memory, known as spacers, from chromosomes of related species in the environment. The presence of these spacers reduces gene exchange between lineages, indicating that CRISPR-Cas contributes to diversification. We have also shown that such inter-species mating events induce the acquisition of spacers against a strain's own replicons, supporting a role for CRISPR-Cas systems in generating deletions in natural plasmids and unessential genomic loci, again increasing genome diversity within populations. Here we aim to test our hypothesis that CRISPR-Cas systems increase within-population diversity, and quantify their benefits to both cells and populations, using large-scale genomics and experimental evolution. We will explore how these systems alter the patterns of recombination within and between species, and explore the potential involvement of CRISPR-associated proteins in cellular DNA repair. This work will reveal the eco-evolutionary role of CRISPR-Cas systems in shaping microbial populations, and open new research avenues regarding additional roles beyond anti-viral defense

Mots-clés : lateral gene transfer,horizontal gene transfer,archaea,crispr cas,genome diversity
Projet ERC : AntiCamp (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Campylobacter jejuni is the most common foodborne contamination in Europe, affecting millions of people, and costing billions of Euros. Current procedures to treat this contamination do not offer sufficient solutions. Here I present a unique approach to eradicate the pathogen from food by utilizing a cost-effective and safe product that does not alter the taste, texture, or appearance of the food. This innovation involves a spray composed of proprietary phage-based particles, which inject antibacterial genes into C. jejuni, thus killing the pathogen. Current phage-based technologies for decontaminating food encounter a major hurdle, because large-scale phage production in the fastidious and pathogenic C. jejuni strain is highly challenging. However, a major advantage of my product is that it can be prepared in a safe and easy-to-grow Escherichia coli host rather than in C. jejuni. Another significant advantage is that the technology producing the phages enables rapid and efficient modifications to the phage-based particles. This platform thus allows easy isolation and manufacture of cocktails of phage-based particles able to target a variety of pathogenic serotypes of C. jejuni. Furthermore, the proprietary particles all have a common scaffold, thus simplifying the regulation, safety, and route of manufacture. I propose a clear commercialization activity with a highly qualified team that I recruited, from both the scientific and commercialization fields. Developing and commercializing this product will provide a proof-of-concept to demonstrate the strength of this approach and will thus pave the way for additional innovative materials based on this technology.

Mots-clés : foodborne disease,antimicrobials,spray,bacterial pathogens,escherichia coli
Projet ERC : SPINNER (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Uppsala University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Can spin integrated circuits (Spin-ICs) with low power-high speed processing capabilities be realized? What are the key ingredients necessary to catapult present-day spintronics to make such a leap? The emergence of two-dimensional (2D) quantum crystals provides new impetus for exploring ambitious ultralow-power and ultrafast speed prospects of spintronics and nanomagnetism. Atomically thin 2D quantum materials like graphene have created novel possibilities for pure spin current communication, functionalities, and controlling spin phenomena, for inventing entirely new kind of spin components, that could pave the way for spin ICs. SPINNER aims to unleash these prospects leveraging the PI’s pioneering leadership and recent innovations in flexible graphene spin circuits, breakthrough longest spin communication in graphene, and precision characterization of 2D magnetic crystals, aiming for three highly ambitious objectives: (1) Achieving strain control of spin currents and spin Hamiltonian in 2D materials. (2) Enabling field-free pure spin current torque functionalities in graphene spin circuits. (3) Controlling ultrafast spin currents at 2D spinterfaces. The proposed new experiments in SPINNER build upon the PI’s expertise in state-of-the-art spin and charge transport, µ-Hall magnetometry, advanced nanofabrication, and device engineering, augmented with new strengths in magneto-optic Kerr effect and ultrafast spin dynamics experiments. Designed for unprecedented engineering of spin materials and devices, the success of SPINNER will reveal new performance, low-power spin functions, determining the ultimate efficiency and speed of pure spin-current operations for Spin-ICs, leading to multiple new scientific and technological breakthroughs. Realizing SPINNER will make a significant impact on 2D quantum materials, flexible nanoelectronics, nanomagnetism and spintronics, and device physics, proving its high multidisciplinary worth.

Mots-clés : graphene,two dimensional materials,flexible nanoelectronics,nanomagnetism,ultrafast spin dynamics
Projet ERC : HERITAGE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Lancaster University — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 485137.5 €

Can states promote economic development without infringing upon their cultural heritage? Although economic globalization and international economic governance have spurred a more intense dialogue and interaction among nations - potentially promoting cultural diversity and providing the funds to recover and preserve cultural heritage - these phenomena can also jeopardize the cultural wealth of nations. Trade in cultural products can lead to cultural homogenization and even to cultural hegemony. In parallel, foreign direct investments have an unmatched penetrating force with the ultimate capacity of changing landscapes and erasing memory. At the same time, the increase in global trade, economic integration and foreign direct investment has determined the creation of legally binding and highly effective regimes that demand states to promote and facilitate trade and foreign direct investment. Has an international economic culture emerged that emphasizes productivity and economic development at the expense of cultural wealth? Does the existing legal framework adequately protect the cultural wealth of nations vis-à-vis economic globalization? Could existing mechanisms in international and European law constrain negative effects of globalization? HERITAGE aims to map the interaction between economic globalization and each specimen of cultural heritage - world heritage, cultural diversity, intangible cultural heritage, indigenous heritage and underwater cultural heritage - in international and European law by investigating the relevant case law before international courts and tribunals. The study adopts an interdisciplinary approach; the relevant cases will be investigated in consideration of both their legal and cultural relevance. The main outcome of this research project will be a monograph written by the principal investigator to be published by a major international publisher; and a number of articles to be published in major international journals.

Mots-clés : cultural heritage,cultural diversity,international trade,foreign direct investment,economic development,dispute settlement,peaceful relations among nations
Projet ERC : CartiLube (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1901058.0 €

Can we exploit insights from the remarkably lubricated surfaces of articular cartilage, to create lubricants that may alleviate osteoarthritis (OA), the most widespread joint disease, affecting millions? These, succinctly, are the challenges of the present proposal. They are driven by our recent finding that lubrication of destabilised joints leads to changes in gene-regulation of the cartilage-embedded chondrocytes to protect against development of the disease. OA alleviation is known to arise through orthopedically suppressing shear-stresses on the cartilage, and a central premise of this project is that, by reducing friction at the articulating cartilage through suitable lubrication, we may achieve the same beneficial effect on the disease. The objectives of this project are to better understand the origins of cartilage boundary lubrication through examination of friction-reduction by its main molecular components, and exploit that understanding to create lubricants that, on intra-articular injection, will lubricate cartilage sufficiently well to achieve alleviation of OA via gene regulation. The project will examine, via both nanotribometric and macroscopic measurements, how the main molecular species implicated in cartilage lubrication, lipids, hyaluronan and lubricin, and their combinations, act together to form optimally lubricating boundary layers on model surfaces as well as on excised cartilage. Based on this, we shall develop suitable materials to lubricate cartilage in joints, using mouse models. Lubricants will further be optimized with respect to their retention in the joint and cartilage targeting, both in model studies and in vivo. The effect of the lubricants in regulating gene expression, in reducing pain and cartilage degradation, and in promoting stem-cell adhesion to the cartilage will be studied in a mouse model in which OA has been induced. Our results will have implications for treatment of a common, debilitating disease.

Mots-clés : boundary lubrication,biological lubrication,cartilage friction and lubrication,biolubrication and mechanotransduction,osteoarthritis,cartilage lubrication and gene regulation
Projet ERC : CFS modelling (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 604610.0 €

Cancer and other diseases are driven by genomic alterations initiated by DNA breaks. Within our genomes, some regions are particularly prone to breakage, and these are known as common fragile sites (CFSs). CFSs are present in every person and are frequently sites of oncogenic chromosomal rearrangements. Intriguingly, despite their fragility, many CFSs are well conserved through evolution, suggesting that these regions have important physiological functions that remain elusive. My previous background in genome editing, proteomics and replication-born DNA damage has given me the tools to propose an ambitious and comprehensive plan that tackles fundamental questions on the biology of CFSs. First, we will perform a systematic analysis of the function of CFSs. Most of the CFSs contain very large genes, which has made technically difficult to dissect whether the CFS role is due to the locus itself or to the encoded gene product. However, the emergence of the CRISPR/Cas9 technology now enables the study of CFSs on a more systematic basis. We will pioneer the engineering of mammalian models harbouring large deletions at CFS loci to investigate their physiological functions at the cellular and organism levels. For those CFSs that contain genes, the cDNAs will be re-introduced at a distal locus. Using this strategy, we will be able to achieve the first comprehensive characterization of CFS roles. Second, we will develop novel targeted approaches to interrogate the chromatin-bound proteome of CFSs and its dynamics during DNA replication. Finally, and given that CFS fragility is influenced both by cell cycle checkpoints and dNTP availability, we will use mouse models to study the impact of ATR/CHK1 pathway and dNTP levels on CFS instability and cancer. Taken together, I propose an ambitious, yet feasible, project to functionally annotate and characterise these poorly understood regions of the human genome, with important potential implications for improving human health.

Mots-clés : mouse models,genomic instability,replication stress
Projet ERC : CFS modelling (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : Partner
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 895101.0 €

Cancer and other diseases are driven by genomic alterations initiated by DNA breaks. Within our genomes, some regions are particularly prone to breakage, and these are known as common fragile sites (CFSs). CFSs are present in every person and are frequently sites of oncogenic chromosomal rearrangements. Intriguingly, despite their fragility, many CFSs are well conserved through evolution, suggesting that these regions have important physiological functions that remain elusive. My previous background in genome editing, proteomics and replication-born DNA damage has given me the tools to propose an ambitious and comprehensive plan that tackles fundamental questions on the biology of CFSs. First, we will perform a systematic analysis of the function of CFSs. Most of the CFSs contain very large genes, which has made technically difficult to dissect whether the CFS role is due to the locus itself or to the encoded gene product. However, the emergence of the CRISPR/Cas9 technology now enables the study of CFSs on a more systematic basis. We will pioneer the engineering of mammalian models harbouring large deletions at CFS loci to investigate their physiological functions at the cellular and organism levels. For those CFSs that contain genes, the cDNAs will be re-introduced at a distal locus. Using this strategy, we will be able to achieve the first comprehensive characterization of CFS roles. Second, we will develop novel targeted approaches to interrogate the chromatin-bound proteome of CFSs and its dynamics during DNA replication. Finally, and given that CFS fragility is influenced both by cell cycle checkpoints and dNTP availability, we will use mouse models to study the impact of ATR/CHK1 pathway and dNTP levels on CFS instability and cancer. Taken together, I propose an ambitious, yet feasible, project to functionally annotate and characterise these poorly understood regions of the human genome, with important potential implications for improving human health.

Mots-clés : mouse models,genomic instability,replication stress
Projet ERC : Secret Surface (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Cancer development is characterized by uncontrolled proliferation, cell survival and metabolic reprogramming. Tumour cells are surrounded by a fluid-mosaic membrane that contains tetraspanins (Tspans) which are evolutionary conserved proteins important in the formation of multiprotein complexes at the cell surface (‘tetraspanin web’). Increasing evidence indicates that Tspans are involved in cancer, still the architecture of the Tspan web in native tumour membranes and its (patho)physiological functions have not been resolved. Based on my preliminary data, I hypothesize that tumour cells contain a disrupted Tspan web in which Tspan interactions are modified leading to aberrant metabolic signalling and tumour development. This is supported by my discovery that loss of Tspan CD37 leads to spontaneous lymphomagenesis due to activation of the Akt survival pathway. The overall aim of Secret Surface is to unravel the composition, physiological functions and molecular mechanisms of the Tspan web on tumour development and clinical outcome. To achieve this, I will focus on studying lymphomas using a multidisciplinary approach: I. Detailed analyses of Tspan web composition in lymphoma to select clinically relevant Tspans (high-throughput tissue microarray technology, multispectral imaging). II. Resolve the endogenous Tspan web on lymphoma cells (super-resolution microscopy), and generation and analysis of lymphoma cells that have a complete deficiency of multiple Tspans (CRISPR/Cas9 technology). III. Decipher molecular mechanisms underlying Tspan web function in lymphoma cells (membrane organization, membrane-proximal signalling, metabolic reprogramming). With my unique toolbox of Tspan knock-outs coupled to advanced microscopy and metabolic studies, I expect that Secret Surface will lead to a new concept in cellular physiology in which cell surface organization by the Tspan web drives tumour development, which may open new horizons for the generation of new cancer therapies.

Mots-clés : lymphoma,cellular physiology,plasma membrane,signal transduction,super resolution imaging