Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : NIMM (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : CIC biomaGUNE — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 149952.0 €

Antibody-detection related to disease or to drug monitoring demands novel IVD tests that provide robust, rapid and early- stage diagnostics for improved and early on-set treatments. However, companies developing novel IVD immunoassays face an important barrier related to reimbursement policy issues when the IVD tests are introduced into national health systems. This barrier discourages many companies from pursuing the development of novel diagnostic tests because the investment necessary to introduce novel IVD tests in the market is hardly matched by the return of the investment. NIMM aims at providing a platform for the development of accurate, sensitive and inexpensive immunoassays for antibody-related conditions using a novel fluorescent nanosensor-based technology. The outcome of the project will pave the way to a commercial product to be sold in the Immunochemistry/Immunoassay segment of the IVD market, currently valued at 15 USD billion. Potential stakeholders in the outcome of NIMM include Public Health authorities and pharmaceutical companies.

Mots-clés : in vitro diagnostics,ivd test,antibody detection,antibody related disorders,fluorescence emitting systems,nanosensors
Projet ERC : PlasmaCellControl (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Research Institute of Molecular Pathology — Pays : Autriche — Rôle : PI
Acronyme de l'entité : IMP
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2500000.0 €

Antibody-secreting cells consisting of short-lived proliferating plasmablasts and long-lived quiescent plasma cells are essential for the acute response to infection and long-term protection of the host against pathogens. Only a few regulators (Blimp1, IRF4, XBP1, Aiolos, Ikaros and E-proteins) have been implicated in the transcriptional control of antibody-secreting cells, and their target genes, with the exception of Blimp1 and E-proteins, are still unknown. This proposal aims to systematically identify key players in the development and function of antibody-secreting cells by using the CRISPR/Cas9 and Cre/loxP methods. For this, we improved existing protocols to extend the duration of in vitro plasmablast differentiation and showed that Rosa26(Cas9/+) B cells infected with Blimp1 or Xbp1 sgRNA-expressing retroviruses recapitulated the Blimp1 and Xbp1 mutant phenotypes in this proof-of-principle experiment. Moreover, Cre retrovirus-mediated deletion of Irf4, Ikaros and Aiolos strongly impaired plasmablast differentiation in this optimized system. To discover new regulators of plasma cell differentiation, CRISPR/Cas9-based screens will be performed with pooled sgRNA libraries targeting all known upregulated genes in plasmablasts and plasma cells, followed by individual validation of the best hits. Selected top-ranked genes will be analyzed in vivo by conditional mutagenesis with newly generated, plasma cell-specific Cre lines. Regulated target genes of IRF4, Ikaros, Aiolos, XBP1 and the XBP1-regulated transcription factor Bhlha15 will be identified in plasmablasts by ChIP- and RNA-seq analyses. Target genes with potentially interesting functions will be further characterized by CRISPR/Cas9- or Cre/loxP-mediated mutagenesis. These experiments will provide fundamentally new insight into the molecular mechanisms controlling the development and function of antibody-secreting cells, which are the essential effector cells of humoral immunity.

Mots-clés : plasma cell development and function,crispr,cas9 screen for key regulators,conditional cre mediated mutagenesis,target genes of plasma cell specific transcription factors,transcriptional networks
Projet ERC : vAMRes (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Toscana Life Sciences — Pays : Italie — Rôle : PI
Acronyme de l'entité : TLS
Type d'entité : Recherche
Financement ERC de l'entité : 2432500.0 €

Antimicrobial Resistance (AMR) is perhaps the most emerging alarm in health. It already causes 700,000 deaths per year and the forecast for 2050 is 10 million deaths, more than cancer today. WHO, UN General Assembly, World Bank, G20, EU, UK and USA governments call for new antibiotics, but the pipeline for new antibiotics is not very promising. Here we propose to use new technologies to develop human monoclonal antibodies and vaccines against three AMR bacteria such as gonococcus, pneumococcus and E.coli. The technology defined as reverse vaccinology 2.0, already successful for viral infections, will be used for bacterial vaccines. Taking advantage of the recent possibility of high throughput cloning of human B cells from convalescent or vaccinated people we aim to find targets difficult or impossible to be discovered using conventional technologies. B cells will be cloned from people convalescent from target infections and from people vaccinated with Men B vaccine which confers some protection against gonococcus. The antibodies produced by the clones will be screened for their ability to bind, intoxicate or kill bacteria using a novel high-throughput microscopy platform that rapidly captures digital images and also with conventional, lower throughput technologies such as bactericidal, opsono-phagocytosis and FACS assays. The selected antibodies, will be expressed as full length and used for passive immunization in animal models and tested for protection in vivo. Finally, those antibodies that will provide the best protection in the above assays, will be used to identify the recognized antigens. Selected antigens will be expressed and tested in vaccine formulations. Fab fragments can be used to make co-crystals with the antigen and determine the crystal structure of the new antigens, for the development of structure-based antigen design. In conclusion we expect to enable development of human monoclonal antibodies and vaccines against AMR.

Mots-clés : vaccines,infectious diseases,monoclonal antibodies,antimicrobial resistance  amr
Projet ERC : SCENT (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Universidade Nova de Lisboa — Pays : Portugal — Rôle : PI
Acronyme de l'entité : NOVA
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Antimicrobial resistant bacteria are a global threat spreading at an alarming pace. They cause over 25,000 annual deaths in the EU, and represent an economic burden exceeding €1.5 billion a year. Current methods for microbial detection in clinical settings take about 24-36 h, but for slow-growing bacteria, as those causing tuberculosis, it can take more than a week. Early-detection and confinement of the infected individuals are the only ways to provide adequate therapy and control infection spread. Thus, tools for rapid identification of bacterial infections are greatly needed. The analysis of microbial volatile metabolites is an area of increasing interest in diagnostics. Recent works demonstrate that fast microbial identification is possible with chemical nose sensors. These sensors usually present limited stability and selectivity, and require aggressive conditions during processing and operation. Bioinspired nose sensors employing biological olfactory receptors are an alternative. Unfortunately, their complexity and low stability are a limitation. My group recently discovered a new class of stimulus-responsive gels which tackle these key challenges. Our gels are customisable and have a low environmental footprint associated. I intend to further explore their potential to advance the field of odour detection, while providing new tools for the scientific community. I will focus specifically in fast microbial detection. To accomplish this, I propose to 1) build libraries of hybrid gels with semi-selective and selective properties, 2) generate odorant specific peptides mimicking olfactory receptors, 3) fully characterise the gels, 4) assemble artificial noses for analysis of microbial volatiles, 5) create databases with organism-specific signal signatures, 6) identify pathogenic bacteria, including those with acquired antimicrobial-resistances. This project is a timely approach which will place Europe in the forefront of infectious disease control.
Projet ERC : FAITh (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Anxiety and stress-related conditions represent a significant health burden in modern society. Anxiety disorders are currently treated with a variety of agents targeting synaptic mechanisms. These agents either directly affect neurotransmitter receptor systems or modulate neurotransmitter levels or availability, but their long-term use is limited by problematic side effects and suboptimal efficacy. The development of new anxiolytic drugs has been fraught with difficulty, hence there is a need for new targets and new avenues for therapeutic development. Importin-dependent transport mechanisms link synapse to nucleus in a diversity of physiological contexts, rendering them potentially interesting targets for behavioural control. However importins and related molecules have not been evaluated for roles in anxiolysis to date. We discovered the roles of importins in axonal injury signaling and in cell size sensing. During the course of our current ERC Advanced grant, and as part of one of the aims, we have conducted comprehensive phenotyping of importin mouse mutants to identify in vivo consequences of the deregulation of size control pathways. One importin mutant line presented a specific phenotype in anxiety tests, and follow-up analyses identified a new molecular pathway for anxiety regulation, and approved drugs affecting this pathway that can be repositioned for anxiety treatment. In this PoC, we will (1) carry out IP protection on our initial identifications of anxiolytic drugs; (2) further validate the anxiolytic activities of these drugs and their closely related structural or functional analogs; and (3) devise an HTS-compatible assay for targeting the importin involved and conduct a pilot screen of ~200,000 compounds in this assay to identify new drug leads for anxiety treatment. As a final step, we will carry out (4) additional IP protection and pre-commercialisation tasks for maximizing the commercialisation potential of our discovery.

Mots-clés : anxiety,anxiolysis,drug discovery
Projet ERC : PEDAL (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Trinity College Dublin — Pays : Irlande — Rôle : PI
Acronyme de l'entité : TCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1447410.0 €

Applying photovoltaic (PV) panels to buildings is an important application for wider PV deployment and to achieving our 20% Renewable Energy EU targets by 2020. PEDAL will develop a disruptive PV technology where record increases in efficiency are achieved and costs dramatically reduced; (1) Diffuse solar radiation will be captured to produce higher efficiencies with concentration ratios over 3 in plasmonically enhanced luminescent solar concentrators (PLSC). Current LSC efficiency achieved is 7.1%, [1]. This proposal will boost efficiency utilising metal nanoparticles (MNP) tuned to luminescent material type in LSCs, to induce plasmonic enhancement of emission (PI and team have achieved 53% emission enhancement). MNP will be aligned to enable directional emission within the LSC (being patented by PI and team). These are both huge steps in the reduction of loss mechanisms within the device and towards major increases in efficiency. (2) Plasmonically enhanced luminescent downshifting thin-films (PLDS) will be tailored to increase efficiency of solar cells independent of material composition. MNP will be used, where the plasmonic resonance will be tailored to the luminescent species to downshift UV. MNP will be aligned to enable directional emission within the PLDS layer, reducing losses enabling dramatic increases in a layer adaptable to all solar cells. (3) These novel systems will be designed, up-scaled and a building integrated component fabricated, with the ability not only to generate power but with options for demand side management. Previous work has been limited by quantum efficiency of luminescent species, with this breakthrough in both the use of MNP for plasmonic emission enhancement and alignment inducing directionality of emission, will lead to efficiencies of both PLSC and PLDS being radically improved. PEDAL is a project based on new phenomena that will allow far reaching technological impacts in solar energy conversion and lighting.

Mots-clés : solar energy systems
Projet ERC : EPIFISH (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Nord University — Pays : Norvège — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1996189.0 €

Aquaculture is the fastest growing food production sector in the world, since there is an increasing demand for fish protein to feed a growing global population, which cannot be met by fisheries. In order to ensure the sustainability of this sector it is critical to domesticate and selectively improve the major commercial fish species. To date, the genetic markers used in selective breeding of fish account only for a fraction of the observed phenotypic variation. EPIFISH is a scientifically innovative and timely project that will address fish domestication and selection from a new perspective using a multidisciplinary approach. The rapid pace of substantial phenotypic changes during adaptation to new environmental conditions in fish undergoing domestication raises the original hypothesis that epigenetic mechanisms are involved in this process. Thus, the overarching aim of EPIFISH is to ascertain the importance of epigenetics in fish domestication using the Nile tilapia (Oreochromis niloticus) as model species. Specific objectives are i) to determine how selection affects the miRNA transcriptome and the epigenetic landscape during domestication, ii) to perform a functional characterization of miRNA variants and epigenetic alleles associated with growth, and iii) to validate them as potential epigenetic markers for future selective breeding programmes. The identification of epigenetic markers will be a ground-breaking element of EPIFISH with major impact on aquaculture biotechnology, since they will enable the development and application of epigenomic selection as a new feature in future selective breeding programmes. Moreover, the project outcomes will provide novel mechanistic insights into the role of epigenetics in fish domestication, which will surely open new horizons for future frontier research in epigenetics, namely transgenerational inheritance and nutritional epigenetics.

Mots-clés : nile tilapia,domestication,selective breeding,mirna,dna methylation
Projet ERC : Q-ARCTIC (Horizon 2020, appel 2020, Synergy grants)
Entité participante : B. geos gmbh — Pays : Autriche — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2551639.04 €

Arctic permafrost has been identified as a critical element in the global climate system, since it stores a vast amount of carbon that is at high risk of being released under climate change. The feedbacks between permafrost carbon and climate change are moderated by many factors, including hydrology, topography, and biology. Shifts in these factors lead to highly complex feedbacks between biogeochemical and biogeophysical processes. These are only rudimentarily represented in current Earth System Models (ESMs), in particular due to a scaling gap between processes and model grid. Q-ARCTIC will establish a next generation coupled land-surface model that explicitly resolves highest resolution landscape features and disturbance processes in the Arctic. Model development will be informed by novel remote sensing methodologies linking landscape characteristics and change potential at an exceptional level of detail. Interdisciplinary observations at multiple spatiotemporal scales will deliver novel insight into permafrost carbon cycle processes. All components are essential for our objective to generate an unprecedented process-based hindcast of glacial permafrost carbon state and projection of permafrost sustainability under future scenarios with a focus on abrupt changes. Our ground-breaking research is based on the newly developed ICON-ESM that enables highest-resolution simulations based on high-performance computing infrastructure. The required remote sensing information can for the first time be produced from new pan-Arctic data streams, such as the European Sentinel satellites. Finally, recent breakthroughs in ultraportable instrumentation and mobile air- and water-borne platforms facilitate bridging the gap between in-situ process understanding and landscape-scale surface-atmosphere exchange. The Q-ARCTIC PI-consortium will combine their world-leading expertise in these fields to close the scaling gap between high-resolution processes and the coarser ESM resolution.

Mots-clés : permafrost,carbon cycle,climate feedback,arctic climate change,hydrological disturbance,scaling,glacial co2
Projet ERC : SEA (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Vrije Universiteit Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : VU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1683384.0 €

Argumentation -the practice of giving and asking for reasons to support claims - is a key component of scientific inquiry, legal procedures, and political life. But in many instances, argumentation does not achieve its presumed goal of fostering consensus and circulation of reliable information. Recent events in world politics - Brexit, US elections, refugee crisis - demonstrate that a better grasp of what argumentation can and cannot do for us is urgently needed. The key question of this project is: ‘what does it take for a process of argumentation to improve our epistemic situation?’ Prior theories fail because they are based on overly idealized assumptions. This project develops a more realistic approach: argumentation is viewed as a practice interwoven with power relations, occurring in situations of epistemic and social diversity, and involving agents who are not ‘purely rational’. We will formulate the first comprehensive account of the social epistemology of argumentation, i.e. of the role of argumentation in processes of circulation and production of knowledge, evidence, and justification. To this end, we will bring together two research traditions that so far remain largely disconnected: social epistemology and argumentation theory. Our innovative hypothesis is that argumentation is a form of social exchange that can be successful to various degrees. What is exchanged are epistemic resources such as knowledge, evidence, justification, critical objections. Insights from social exchange theory will inform the investigation, a suitable framework for our purposes because it emphasizes the interplay between self-interest and interdependence. The result will be a realistic theory of the processes through which epistemic resources are shared and produced through argumentation. It will offer concrete prescriptions on how to optimize these processes, with wide-ranging applications wherever argumentation is crucial: scientific, legal, and political/public discourse.

Mots-clés : argumentation
Projet ERC : LACOPAROM (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999398.0 €

Aromatic compounds are cheap and readily available, making them ideal starting materials for the synthesis of chiral alicyclic compounds, important synthetic building blocks for both natural product synthesis and drug discovery. However, general strategies for efficient, catalytic dearomatisation of aromatics are lacking. This proposal aims to fill this gap by developing general asymmetric methods for dearomatisation reactions of both electron-rich and electron-deficient aromatics. It relies on an innovative approach based on LA activation of the arenes, followed by copper catalyzed carbon-carbon bond forming reactions, with a special focus on environmentally benign and cost-effective processes. To achieve the overall aim of the proposed project, the research program is composed of four distinct but complementary research lines aiming at catalytic asymmetric dearomatisation/carbon-carbon bond forming reactions using: - Electron-deficient carbonyl substituted arenes - Pyridines and other N-containing heteroarenes - Phenols and anilines and fused analogues - Benzylic aromatic systems The remarkable and novel feature of this strategy is that it enables for the first time selective catalytic asymmetric dearomatisations of various classes of aromatic substrates following a general, unified concept. Furthermore, since sequential bond constructions take place in a single synthetic operation, a rapid increase of molecular complexity can be achieved at greatly reduced cost and increased atom-efficiency, thereby contributing to a more sustainable future. Consequently, there is huge potential for this strategy to become an invaluable instrument to access a wide variety of chiral carbocyclic compounds and I anticipate it will have a significant impact in the field of organic synthesis.