Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SYNECT (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2212114.0 €

The immunological synapse is a highly conserved scaffold for communication between immune cells built around cooperation of antigen and adhesion receptors. It often takes the form of a bull’s eye with a central cluster of antigen receptors surrounded by a ring of adhesion molecules. We have recently observed that antigen receptor coated extracellular microvesicles bud directly from the center of the immunological synapse- which we define as synaptic ectosomes. Synaptic ectosomes are transferred to the antigen- presenting cell and can generate signals after the T cell-APC synapse has dissolved. We aim to determine the composition of synaptic ectosomes, determine their fate in the antigen-presenting cell and identify approaches to manipulate their formation in vivo. The objectives will be to 1) isolate synaptic ectosomes from human T cells and determine their molecular composition; 2) determine the functional impact of synaptic ectosomes on the antigen presenting cell; and 3) use gene targeting to control the process in vivo to understand its role in T function of helper, cytotoxic and regulatory T cells. The technologies will include microscopy, proteomics, genomics, and in vivo models with constitutive and conditional gene targeting. This work will address fundamental gaps in our understanding of immune cell communication.

Mots-clés : immunological synapse,adhesion,microscopy
Projet ERC : PROBIt (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Aston University — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2226923.0 €

The impact of insults to the developing brain upon cognition and behaviour has far-reaching consequences for the child, their family, education and health care systems, and government expenditure. Many variables (illness, environmental) contribute to different outcomes following similar insults, and they exert their influence via the child’s developing brain. Predicting which child will recover from early brain insult and identifying those at risk of poor outcome represents a major challenge, with significant health economic implications. An unexplored question is whether direct measurement of the structure and function of the developing brain can improve our ability to predict outcomes in the long-term. Thus, PROBIt aims to assess the utility of brain imaging biomarkers to predict individual neuropsychological and neurobehavioural outcomes following paediatric brain injury, and to identify those factors that combine optimally to classify outcomes. The proposal adopts an unorthodox approach of combining heterogeneous injury groups to explore the structural and functional consequences of perturbing developing brain networks. PROBIt integrates data from clinically relevant paediatric cognitive and behavioural assessment, neuroimaging and computational modelling in large cohorts of children with brain insults. Multivariate pattern analysis will be used to train a statistical classifier to reliably predict individual child outcomes across three core domains: achievement, behaviour and cognitive ability. PROBIt significantly advances our understanding of features that confer risk and resilience to different neurodevelopmental outcomes and has important implications for clinical diagnosis and rehabilitation of children with early brain insults.

Mots-clés : early brain injury,clinical child neuropsychology,mri scanning,cognition,behaviour
Projet ERC : FASTLabEx (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Commissariat à l’énergie atomique et aux énergies alternatives — Pays : France — Rôle : PI
Acronyme de l'entité : CEA
Type d'entité : Recherche
Financement ERC de l'entité : 1999431.0 €

The impact of synthetic organic molecules on health, life quality and lifestyle is beyond doubt. It is therefore of fundamental importance to detect and quantify the fate of organic compounds and provide a precise risk/benefit assessment, before they reach the market and large public exposure. The traceless incorporation of carbon-14 allows tracking organic molecules and provides vital knowledge on their fate. This information is critical for pharmaceutical development, crop science and human food safety evaluation. Surprisingly, carbon radiolabeling still represents a bottleneck and an unsolved fundamental problem. In fact, current synthetic strategies are marred by several major drawbacks, including the generation of radioactive waste, being multi-step time-consuming and high resource-demanding. To circumvent such disadvantages, I present FASTLabEx, a novel approach for the straightforward preparation of carbon-labeled complex organic molecules that introduces the radioactive tag at the ultimate-stage of the synthesis. Inspired by efficient metal-catalyzed transformations, FASTLabEx makes use of a novel paradigm of “carbon isotope exchange”, defined as the selective replacement of molecular moieties into organic molecules, by reversible molecular deconstruction/reconstruction in presence of an appropriate radiolabeled moiety. FASTLabEx will explore this concept onto a large variety of functional groups and structural diversity, far beyond the case of carboxylic acids. This approach has the potential to streamline the radio-synthesis of pharmaceuticals and agrochemicals. Outcomes from FASTLabEx will have a tangible societal impact not only for the radiochemical community, but also for pharmaceutical and agrochemical industries and in fine the consumers and patients. In order to mitigate the risks inherent to the project, preliminary results demonstrate its feasibility.

Mots-clés : carbon 14,radiolabeling,isotopic labeling,isotope exchange,carbon dioxide,carbon monoxide
Projet ERC : RiboTrace (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Vienna — Pays : Autriche — Rôle : PI
Acronyme de l'entité : Univie
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1448149.5 €

The implementation of distinct gene expression profiles is essential for organismal development, physiological responses to external stimuli or pathogens, and defines a primary cause for human disease. While much attention has been paid to the regulation of transcription, the control over RNA fate and function has only recently emerged as a central hallmark of gene regulation with enormous biological, technological and biomedical implications. Here, we propose to study the molecular principles of RNA silencing, the least understood aspect of post-transcriptional gene regulation. We aim to systematically dissect the mechanisms and biological functions of RNA 3´end uridylation to determine the emerging role of RNA modifications in the regulation of gene expression; we will elucidate fundamental principles of RNA turnover at the genomic scale by time-resolved transcriptomics; and we will use functional genomics and haploid genetics to systematically delineate post-transcriptional gene regulatory pathways. Throughout, we will link our results back to the established function of RNA silencing in the control of organismal development, physiology and disease. Our goal is to acquire fundamental insights into the processes that survey the quality and quantity of the transcriptome to determine possible molecular causes for aberrant RNA levels that have been associated with diverse human diseases. Because of its genetic and biochemical tools, we will use Drosophila melanogaster as a model organism. We will employ a combination of in vivo genetics, cell-free biochemical experiments, bioinformatics, and cell culture methods. What we learn in flies we will test for its conservation in mammalian cell extracts and cultured cells. Overall, we will determine fundamental biological mechanisms of gene regulation trough pathways with enormous biological impact in health and disease.

Mots-clés : rna silencing,rna metabolism,rnp enzymology,rna modifications,rna uridylation,rna decay,post transcriptional gene regulation,time resolved rna profiling
Projet ERC : ENVIROIMMUNE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : TU Dresden — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : TUD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

The incidence of autoimmune diseases in developed societies is increasing at high rates, but the underlying cause for this phenomenon has not been elucidated yet. Since the genetic architect remains considerably stable, this increase is likely associated with changes in the environment. Autoimmunity is linked to an imbalance of pro-inflammatory Th17 cells and anti-inflammatory Foxp3+ regulatory T cells (Treg). However, little is known regarding environmental factors that influence the Th17/Treg balance. We recently discovered that a sodium-rich diet severely exacerbates experimental autoimmune encephalomyelitis (EAE) through an increased induction of pathogenic Th17 cells. Surprisingly, our preliminary data indicate that high-salt conditions also significantly impair Treg function, resembling a phenotype observed in several human autoimmune diseases. In addition, we have evidence that a high-salt diet affects the gut microbiota, implicating possible indirect effects on immune cells in vivo. Based on these findings we hypothesize that excess dietary salt represents an environmental risk factor for autoimmune diseases by modulating the Th17/Treg balance by several direct and indirect mechanisms. To address this hypothesis we will 1) examine the underlying mechanisms of high-salt induced Treg dysfunction and effects on the Treg/Th17 balance by molecular and functional analysis in vitro and compare it to known risk variants of human autoimmune diseases, and 2) define direct and indirect effects of excess dietary salt on the Th17/Treg balance and autoimmunity in vivo and explore potential novel pathways for targeted interventions. Thus, the proposed study will uncover the impact of a newly discovered environmental modulator of the immune cell balance and will ultimately pave the way for new approaches in therapy and prevention of autoimmune diseases.

Mots-clés : autoimmunity
Projet ERC : EXODUS (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998063.0 €

The incidence of autoimmune diseases including multiple sclerosis is dramatically increasing. While there is a genetically defined “bedrock” susceptibility to develop T cell mediated autoimmunity, environmental cues likely determine the threshold for disease development. Yet, little is known on how environmental cues sensed at body/environment interfaces are translated into immunopathology in distant organs like the central nervous system (CNS). Here, we raise the hypothesis that immune cells must be activated at epithelial surfaces and then physically migrate to distant organs in order to induce autoimmunity. Furthermore, we propose that the “state of activation” of (either lymphoid or myeloid) immune cells can be interrogated by IL-6 production since IL-6 deficiency confers resistance to virtually any organ specific autoimmune disease and we have contributed fundamentally in defining the role of IL-6 for the generation of Th17 cells that are highly associated with autoimmune tissue inflammation. In EXODUS, we will develop ground-breaking next generation reporter tools in order to test these hypotheses. A split Cre recombinase protein, which dimerizes and is activated by blue light, will be used to genetically label cells (and their progeny) in a topologically defined manner (“compartment reporter”). Furthermore, we have developed a novel type of Cre-inducible in vivo IL-6 reporter (“activation reporter”). The combination of these tools will enable us to trace the anatomical compartment of activation of immune cells without limitations in lag time. Thus, site specific photogenetic co-induction of a fluorescence and IL-6 reporter will be used to probe peripheral sites for their potency to licence immune cells to travel to the CNS (Forward). Vice versa, labeling of cells in the CNS (through a thinned skull window) will allow for studying immune cell exodus from the CNS in homeostasis and during inflammation (Reverse).

Mots-clés : immune cell trafficking,cytokines
Projet ERC : TreeGraSP (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Heinrich Heine University Düsseldorf — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HHU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1995890.0 €

The increasing amount of data available in our digital society is both a chance and a challenge for natural language processing. On the one hand, we have better possibilities than ever to extract and process meaning from language data, and recent techniques, in particular deep learning methods, have achieved impressive results. On the other hand, linguistic research has a much broader empirical basis and can aim at rich quantitative models of language. Unfortunately, theory and application interact too little in these areas of meaning extraction and grammar theory. Current semantic processing techniques do not sufficiently capture the complex structure of language while grammatical theory does not sufficiently incorporate data-driven insights about language. TreeGraSP bridges this gap by combining rich linguistic theory with data-driven approaches to large scale statistical grammar induction and to semantic parsing. The novelty of its approach consists in putting semantics at the center of grammar theory, putting an emphasis on multilinguality and typological diversity, and adopting a constructional approach to grammar. TreeGraSP is interdisciplinary and innovative in serveral respects: It contributes to the field of linguistics by a) making theories of grammar explicit, b) providing a grammar implementation tool for typologically working linguists and c) developing means to obtain a quantitative grammar theory. And it contributes to the field of computational semantics by providing a probabilistic theory of meaning construal that can be used for textual entailment and reasoning applications. The challenge lies in the intended transfer between theoretical linguistics and statistical natural language processing.

Mots-clés : syntax semantics interface,frame semantics,grammar implementation,grammar induction,semantic parsing
Projet ERC : HEIREC (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The increasing demand for food, in the context of a changing climate and deteriorating environments, will be one of the major challenges facing society in the coming decades. However, as breeding a new crop variety currently takes on average 10 years, the predicted changes in food demand and climate are only several breeding cycles away. Meiotic recombination and crossover is a major tool used in crop breeding when diverse strains are hybridized in order to combine useful traits. Therefore, in the current climate of change, there is an urgent need to reduce the time needed to produce new crop varieties, and meiotic recombination is one target to achieve this. In my ERC Consolidator grant SynthHotSpot, we are investigating the molecular control of meiotic recombination using the model plant Arabidopsis. We have identified the gene HEI10, which encodes a conserved meiotic ubiquitin E3 ligase, as a major regulator of crossover numbers. Importantly, during this work we discovered that HEI10 is highly dosage-sensitive and introduction of additional copies of this gene more than doubled crossovers throughout the Arabidopsis chromosome arms. As HEI10 is conserved between plants, fungi and animals, this may provide a gene target to manipulate crossover numbers in diverse species. In light of the demands on breeding companies to develop new, high yielding crop varieties, HEIREC will fast-track the development of a new platform technology to increase recombination frequency during breeding, via introduction of additional HEI10 copies. Within HEIREC we will generate proof of concept data where we increase HEI10 copy number within bread wheat, in order to increase recombination and thereby accelerate crop improvement. Bread wheat is a major crop globally where recombination level limits strain improvement. Therefore, by increasing recombination frequency during breeding, HEIREC will accelerate the development of new crop varieties and contribute to ensuring food security.

Mots-clés : meiosis,crossover,recombination,breeding,crops,food security
Projet ERC : PHII (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : PI
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2497081.0 €

The innate immune system includes a cellular and a humoral arm. Structural diversity is a characteristic of humoral fluid phase pattern recognition molecules. These include complement components, collectins, ficolins, and pentraxins. We have used the long pentraxin PTX3, identified by the applicant (cDNA and genomic, mouse and human), as a prototypic fluid phase pattern recognition molecule to dissect its function, as well as to define general properties of humoral innate immunity and its interplay with the cellular arm. The general objective of this application is to explore unexpected vistas on humoral innate immunity, using PTX3 as a molecular tool. Specifically two hypothesis will be tested based on preliminary data. First the applicant will test the hypothesis that matrix and microbe recognition are related functions of PTX3 and that a microenvironmental signal (acidic pH) sets PTX3 in a matrix recognition, tissue repair mode. A second related line of work will focus on inflammation as a key component of the tumor microenvironment. The applicant will test the hypothesis that PTX3 and elements of the humoral innate immune system are essential components of cancer related inflammation. In particular, based on preliminary data, the hypothesis will be tested that PTX3 acts as an extrinsic oncosuppressor in murine carcinogenesis and in selected human cancers by suppressing the recruitment of tumor-promoting inflammatory cells. These studies are expected to provide new unexpected vistas on the humoral arm of the innate immune system.
Projet ERC : SUMOWO (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : University of Bremen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

The innovative concept of the ERC Starting Grant project “Keratinocytes and Matrix metalloproteinases: driving force of skin wound contraction?” was to use inhalants for skin wounds and it proved to be excellent and functional. Surface Modulation of Wounds (SUMOWO) with these anti-inflammatory, pro-migratory and anti-fibrotic compounds will be beneficial for chronic wound healing and reduce excessive scarring. This novel drug-based treatment strategy marks a novel era of wound care. A clinical phase 1 study on healthy volunteers is planned to show the product’s safety and tolerability for skin use – the first step towards clinical application. The goal of SUMOWO is to deliver clinical proof of concept, to provide a thorough market analysis with contact to key-players, to secure our intellectual property rights on an international platform, to accelerate commercial exploitation and ultimately, to restore patients’ life quality.

Mots-clés : excessive scarring,chronic wounds,leg ulcers,wound healing,surface modulation,scar prevention
Projet ERC : B2C (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 763597.5 €

The intention of Beasts to Craft (B2C) is to document the biological and craft records in parchment in order to reveal the entangled histories of animal improvement and parchment production in Europe from 500-1900 AD. B2C will lay the foundations for a new approach to the the study of parchment manuscripts —biocodicology— which draws evidence from the overlooked first stages in production, the raising of livestock and the preparation of the skins. 1. Parchment is an extraordinary but overlooked high resolution zooarchaeological record and a molecular archive. Livestock genetics is revealing breed diversity and markers of character traits such as fleece quality. B2C will exploit this new-found knowledge, using progressively older dated archival (sheep) parchments to study the history of improvement 1300 - 1900. Visual examination of the skins will search for direct evidence of disease and fleece quality. 2. Craft skills can be read from parchment and, when combined with chemical data and comparison with modern analogues, will produce the first European wide record of the craft from 500-1900. The size and scope of this the parchment archive means it is one of the largest and most highly resolved records of a specialist medieval craft. We will explore how these skills develop and when and where regional patterns appear and decline. These two remarkable records requires a large interdisciplinary team. However biocodicology draws from and informs upon a wide and diverse spectrum of existing scholarship in conservation, the arts and sciences. A third strand of the project will (i) furnish manuscript scholars with some of the information available to the scribe at time of production (ii) inform and shape attitudes to parchment conservation (iii) provide high resolution biological data on animal management, movement and health and (iv) explore methods to link datasets and promote data reuse.

Mots-clés : partchment,craft,improvement