Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : I-PACE (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1968996.0 €

Background: Encephalitis is a severe inflammation of the brain that can be caused by viruses, bacteria and other microorganisms, or autoimmune disease. The impact is high: the case fatality rate is 10-20% and half of patients have neurological deficits. Identifying the cause of encephalitis is essential for early initiation of therapy and thereby improves outcome. The clinical challenge: Current diagnostics for encephalitis are insufficient. My prospective pilot study showed that the cause of encephalitis could be identified in only half of patients. Aim: The aim of I-PACE is to improve the cause-specific diagnosis of encephalitis using innovative diagnostic methods. Methods: I will use my encephalitis network of Dutch hospitals to study innovative diagnostic methods in 3000 patients with suspected encephalitis and validate the results in 2000 patients from Denmark, the UK and Zambia. I will collect clinical data, cerebrospinal fluid (CSF) and blood to enable state-of-the-art diagnostic studies and identify novel causes of encephalitis. First, I will perform virus discovery and DNA metagenomics sequencing to identify new infectious causes of encephalitis, combined with phage-display antibody sequencing. Second, I will perform CSF single cell gene expression studies to identify transcription patterns specific for the cause of encephalitis. Third, single cell immune profiling and anti-neuronal antibody detection assays will be used to identify new causes of autoimmune encephalitis. Finally, I will perform extensive metabolite and lipid analysis in the CSF to identify new biomarkers enabling a syndromic diagnosis to quickly differentiate between causes. Impact: With I-PACE I aim to increase the proportion of patients with a cause-specific diagnosis of encephalitis from 50% to 80%, facilitating direct and targeted treatment to improve the prognosis. I will discover novel causes of infectious and autoimmune encephalitis, and provide insights in its pathophysiology.

Mots-clés : encephalitis,cerebrospinal fluid,anti neuronal antibodies,lipidomics,metabolomics,immune profiling,phage display sequencing
Projet ERC : MYOP-PATH (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Erasmus MC — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Background: Myopia (near-sightedness) is a growing public health issue due to its rapidly rising prevalence. In particular high myopia carries a significant risk of blindness for which there are no treatment options. The disease etiology of this trait is complex and largely unknown. We recently identified a large number of disease loci and genes, which provide significant clues for pathogenic pathways. However, they explain only a limited proportion of myopia’s heritability, and the direct functional effects of risk variants, their interaction with environmental factors, and their potential for intervention are unknown. Aim: To identify disease mechanisms that underlie myopia and create starting points for therapy. Approach: 1. Decipher the genetic background of myopia, identify gene effects and influence of environment in humans. In very large consortia (~250,000 study participants) with ample data on epidemiology, myopia phenotype, and genomic markers, we will exploit the recent technological advances to analyze a large number of genetic variants including those altering protein function. We will annotate significant hits to major pathways, study gene effects on phenotype, identify retinal cell structures which drive myopiagenesis, investigate gene-environment interaction, and develop a prediction model for progression to high myopia. 2. Identify gene effects, influence of environment, and targets for intervention in animals. In mice and zebrafish which have been manipulated for high myopia risk genes, we will study ocular biometry, retinal anatomy, visual behavior, and molecular and biochemical effects of genes as a function of environment. Interventions tailored to altering gene effects will be explored. Impact: Integrating the results obtained from these genetic, epidemiologic, functional and molecular studies will advance our understanding of the underlying biology of myopia and help create novel therapeutic targets to reduce the burden of high myopia.

Mots-clés : eye diseases,refractive error,complex trait genetics,population based cohort studies,retinal imaging,genome wide association,exome sequencing,zebrafish,genetically modified mice
Projet ERC : Growth regulation (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Uppsala University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499765.0 €

Bacteria live in environments where resources for growth are scarce and shared with other bacteria. The ability to inhibit the growth of other bacteria is thus favourable and most bacteria use multiple systems for such antagonistic interactions, including delivery of protein toxins to other bacteria (e.g. bacteriocins, type 6 secretion and contact-dependent growth inhibition systems). In addition to their role in competition, all these toxin delivery systems frequently deliver toxins to cells of the same genotype, i.e. cells immune to the toxic activity, but a function for self-delivery of toxins has never been identified. Recent evidence from our lab suggests that self-delivery of toxins generates population heterogeneity in terms of growth at high cell densities, i.e. upon cell-cell contacts. But if this is a common feature of all toxin delivery systems is not known. Here we will investigate if toxin delivery to cells immune to the toxin creates population heterogeneity in terms of growth, mutation rates and gene expression, and if this is important for bacterial evolution and multicellularity. As homologs for many of the toxins can also be found in eukaryotes, including multicellular organisms, we will investigate if the functions of these systems are also conserved across kingdoms. We will particular characterize the role of bacterial toxin delivery systems for multicellular behaviour and adaptation to new growth environments. This research have important consequences for understanding cell-to-cell contacts and the organization of multicellular tissues in general; from how to control biofilm formation to the understanding of uncontrolled cell growth in higher eukaryotes.

Mots-clés : bacteria,antibiotic,population heterogeneity,multicellularity,persisters,toxins
Projet ERC : SWEETBULLETS (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Helmholtz Centre for Infection Research — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : GBF;HZI
Type d'entité : Recherche
Financement ERC de l'entité : 1499551.0 €

Bacterial infections are now a global threat demanding novel treatments due to the appearance of resistances against antibiotics at a high pace. The ESKAPE pathogens are those with highest importance in the EU and chronic infections due to biofilm formation are a particular task. Noninvasive pathogen-specific imaging of the infected tissue is not clinically available. Its successful implementation will enable the choice of appropriate therapy and boost efficacy. Furthermore, Gram-negative bacteria have a highly protective cellular envelope as an important resistance mechanism for drugs acting intracellularly, resulting in an alarmingly empty drug-pipeline. To overcome this gap, I will establish Lectin-directed Theranostics targeting pathogens via their extracellular carbohydrate-binding proteins at the site of infection for specific imaging and treatment. This will be implemented for the highly resistant ESKAPE pathogen Pseudomonas aeruginosa through 3 different work packages. WP1 Sweet Imaging: Design & conjugation of lectin-directed ligands to imaging probes, Optimization of ligand/linker, in vivo proof-of-concept imaging study. WP2 Sweet Targeting: Delivery of antibiotics to the infection through covalent linking of lectindirecting groups. Employing different antibiotics, assessment of bactericidal potency and targeting efficiency. Manufacturing of nano-carriers with surface exposed lectin-directed ligands, noncovalent charging with antibiotics. In vitro and in vivo targeting. WP3 Sweet SMART Targeting: Conjugates as SMART drugs: specific release of anti-biofilm lectin inhibitor and drug cargo upon contact with pathogen, development of linkers cleavable by pathogenic enzymes. SWEETBULLETS will establish fundamentally novel lectin-directed theranostics to fight these deleterious infections and provide relief to nosocomially infected and cystic fibrosis patients. It is rapidly extendable towards other ESKAPE pathogens, e.g. Klebsiella spp..

Mots-clés : lectin,carbohydrate,glycosciences
Projet ERC : whyBOTher (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Helsinki — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Bacterial toxins cause devastating diseases in humans and animals, ranging from necrotic enteritis to gas gangrene and tetraplegia. While toxin synthesis probably endows these bacteria with a selective advantage in their natural habitats, toxigenesis is likely to represent a fitness cost. It is thus plausible that mild environments encourage bacteria to give up toxin production, or reduce the number of toxigenic cells in populations. The cellular strategies bacteria use to silence toxin production and to establish stably non-toxigenic subpopulations represent targets for innovative antitoxin and vaccine strategies that can be utilized by the food, feed, medical, and agricultural sectors. I have found the first repressor that blocks the production of the most poisonous substance known to mankind, botulinum neurotoxin (BOT). This toxin, also known as “botox”, kills in nanogram quantities and is produced by the notorious food pathogen, Clostridium botulinum. In whyBOTher, I will extend the knowledge from this single regulator to comprehensive understanding of how C. botulinum cultures coordinate BOT production between single cells and cell subpopulations in response to their physical and social environment, and which genetic and plastic cellular strategies the cells take to attenuate BOT production in short and long term. I will experimentally force evolution of BOT-producing and non-producing cell lines, and explore the genetic, epigenetic, and cellular factors that explain the emergence of the two cell lines. To achieve this goal, I will extend the research on C. botulinum biology in two dimensions: from population level to fluorescent single-cell biology, and from genomic information to functional analysis of regulatory and metabolic networks controlling BOT production. whyBOTher represents an unprecedented research effort into regulation of bacterial toxins, and introduces a shift in paradigm from population-level observations to the life of single bacterial cells.

Mots-clés : food safety,food poisoning,clostridium botulinum,clostridium,botulinum neurotoxin,clostridial toxin
Projet ERC : HomeoBalanceExcInh (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Sheffield — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Balanced excitation and inhibition is a fundamental principle of neural circuit function, and perturbed excitation/inhibition (E/I) balance has been linked to diseases such as epilepsy, autism and schizophrenia. Maintaining E/I balance within normal bounds depends in part on homeostatic plasticity, in which neurons compensate for deviations in activity levels by adjusting their responsiveness to excitation and inhibition. Yet despite recent progress in elucidating molecular mechanisms underlying homeostatic plasticity in reduced preparations, little is known about such mechanisms in the intact brain. I propose to address this gap using a simple and genetically tractable neural circuit that I recently characterized. In Drosophila, Kenyon cells (KCs), the neurons underlying olfactory associative memory, receive excitation from projection neurons (PNs) as well as feedback inhibition from a single identified neuron (‘APL’). The balance between these two forces maintains sparse odour coding in KCs, which enhances the odour-specificity of associative memory by reducing overlap between odour representations. Preliminary evidence indicates that KCs adapt to prolonged disruption of E/I balance, providing a ground-breaking opportunity to use the powerful genetic tools of Drosophila to uncover the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in vivo in a defined circuit that mediates a sophisticated behaviour. Specific aims: 1. Characterize homeostatic plasticity in the PN-KC-APL circuit. 2. Identify genes up- and down-regulated in response to perturbations of E/I balance. 3. Determine role of candidate genes and cellular mechanisms in homeostatic plasticity. Establishing the PN-KC-APL circuit as a novel model system for homeostatic plasticity will reveal for the first time the molecular mechanisms underlying homeostatic balancing of excitation and inhibition in the intact brain.

Mots-clés : olfaction,sparse coding,homeostatic plasticity,balance of excitation and inhibition,olfactory memory
Projet ERC : MaeBAia (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499999.0 €

Beta2 agonists (B2as) such as the short acting salbutamol, used to relieve acute wheeze, and the long acting salmeterol used to control asthma with inhaled steroids (ICS), are almost universally used in asthma. However, there is significant concern over morbidity and mortality related to adverse effects, particularly when used without ICS, and/or in excess at exacerbation (mostly caused by rhinovirus [RV] infection). The mechanisms of adverse effects are not understood. This proposal will rock the asthma world by revealing the mechanisms of these adverse effects, thus reducing asthma morbidity and mortality. I discovered that B2as induced, and augmented RV induction (to mimic exacerbation), of the pro-inflammatory mediator IL-6 in bronchial epithelial cells (BECs) in vitro, via a cAMP dependent mechanism. ICS suppressed this induction. Hundreds of asthma-related pro-inflammatory mediators and airway mucins have potential for induction by cAMP, and for suppression by ICS. I hypothesise that adverse effects of B2as are mediated by cAMP-dependent induction of pro-inflammatory mediators/mucins in BECs and macrophages and that ICS protect against induction. I will use RNA-seq to identify all mediators induced by B2as (±RV), and suppressed by ICS, in commercially sourced human BECs and macrophages (Mφ) and in primary BECs and Mφ from 8 mild asthmatics. I will develop qPCR/protein assays for these mediators, to confirm RNA-seq data, and identify mediators to study in vivo. I will study 24 mild asthmatics at baseline, after 14 days inhaled salmeterol and after 14 days inhaled salmeterol/ICS. To mimic B2a overuse at exacerbation, I will study 10 mild asthmatics to investigate the effect of high dose salbutamol. Clinical responses will be comprehensively assessed and airway inflammation will be studied using state of the art methods. It is essential that these studies are executed urgently to inform safest use of current asthma medication, and future drug development programs
Projet ERC : IMA-cRCT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Hospital Sant Joan de Déu Barcelona — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 849825.0 €

Between 3 and 42% of patients do not initiate their treatments. Non-initiation and non-adherence are associated with poorer clinical outcomes, more days of sick leave and higher costs. The aim of this research project is to generate an effective, efficient and feasible intervention that improve initiation and adherence and improves clinical symptoms. The long-term benefits in terms of improved health and reduced costs will be evaluated. The results will be disseminated to stakeholders, decision-makers and the scientific community to promote implementation. The intervention is expected to improve the clinical practice, empowering the patient. The project develops an innovative approach to the design and evaluation of behavioural interventions that uses the principles of complex interventions, pragmatic trials and implementation research. Nine interventions to reduce non-initiation have been tested. The interventions were not theory-based and most used simple reminders. The evidence supporting these interventions was low and their impact on clinical symptoms and cost-effectiveness was not assessed. The strengths of the IMA-cRCT study are: 1) the main stakeholders are involved in the design and assessment; 2) IMA intervention is theory-based and has been optimized; 3) the study will assess the impact of the intervention on clinical parameters and cost-effectiveness, which is key to guarantee its transferability; 4) the project involves decision-makers; 5) the pragmatic design increases generalisation and 6) the intervention is easily transferable to other pathologies, populations and countries. As part of the ERC research project, a pragmatic cluster randomized controlled trial (cRCT) will evaluate the short-term effects of the IMA intervention and its cost-effectiveness and Markov models will be constructed to estimate its long-term cost-effectiveness. The results will be disseminated to facilitate its transferability to clinical practice in Spain and Europe.

Mots-clés : non initiation,adherence,pragmatic trials,complex interventions,cost effectiveness,economic modelling,primary care,cardiovascular disease
Projet ERC : PETRIFYING WEALTH (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Rome Tor Vergata — Pays : Italie — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 586977.0 €

Between the years 1050 and 1300 the European landscape turned to stone. It was a structural transformation that led to the birth of a new, long-lasting panorama and helped in the creation of individual, collective and regional identities: a landscape epitomising the way we see the space and territory of Europe. Petrifying Wealth seeks to rewrite the social history of the central Middle Ages, emphasizing the need to reassess from an untried perspective an element that has always been present in our vision of the period—the sudden ubiquity of masonry construction—but which has hardly been given the opportunity to provide in-depth explanations for complex social dynamics. This project seeks to offer novel explanations to previously unasked questions about wealth, building, and collective identity. The speed, extent, and systematization of the construction of churches, towers, castle walls, palaces, and houses within castles and cities provide evidence of an underlying, if unaddressed, issue. That is, it is precisely in the twelfth and thirteenth centuries that the structural link can most clearly be seen between both private and collective wealth, and the investment in stone structures built to last. Our study of the shift involving new institutional dynamics, but also unprecedented social practices, as well as ideological concepts radically different from those that had prevailed until then, aims to break down assumptions that have naturalized this truly astonishing process while using as case studies the undervalued regions of southern Europe to explore the larger questions. By inverting the standard approach that sees the heart of the former Carolingian empire (present-day France and Germany) as the wellspring from which other “peripheral” territories drank, we bring new light to probe the greater meaning behind the process of masonry building as an investment in social identity in the central Middle Ages.

Mots-clés : central middle ages,social history,masonry building,southern europe,wealth,social identity
Projet ERC : BioELCell (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Aalto University — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2486182.0 €

BioELCell will deliver ground-breaking approaches to create next material generation based on renewable resources, mainly cellulose and lignin micro- and nano-particles (MNC, MNL). Our action will disassemble and re-engineer these plant-based polymers into functional materials that will respond to the demands of the bioeconomy of the future, critically important to Europe and the world. My ambitious, high gain research plan is underpinned in the use of multiphase systems with ultra-low interfacial tension to facilitate nanocellulose liberation and atomization of lignin solution streams into spherical particles. BioELCell will design novel routes to control MNC and MNL reassembly in new 1-D, 2-D and 3-D structures. The systematic methodologies that I propose will address the main challenges for lignocellulose processing and deployment, considering the important effects of interactions with water. This BioELCell action presents a transformative approach by integrating complementary disciplines that will lead to a far-reaching understanding of lignocellulosic biopolymers and solve key challenges in their use, paving the way to functional product development. Results of this project permeates directly or indirectly in the grand challenges for engineering, namely, water use, carbon sequestration, nitrogen cycle, food and advanced materials. Indeed, after addressing the key fundamental elements of the research lines, BioELCell vindicates such effects based on rational use of plant-based materials as a sustainable resource, making possible the generation of new functions and advanced materials. BioELCell goes far beyond what is known today about cellulose and lignin micro and nano-particles, some of the most promising materials of our century, which are emerging as key elements for the success of a sustainable society.

Mots-clés : cellulose,fibres,nanocellulose,colloids,biobased materials,emulsions,foams,dispersions,surface science