Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : OLE-DIOX (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Institut Català d'Investigació Química — Pays : Espagne — Rôle : PI
Acronyme de l'entité : ICIQ;ICIQ-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 149500.0 €

Carboxylic acids are building blocks of utmost importance in our chemical industry, as these motifs are extensively used in the manufacture of soaps, detergents, pharmaceuticals, rubber, plastics, dyes, textile, perfumes, and animal feed, among many others. Current industrial protocols for their synthesis rely heavily on toxic reagents, lengthy-step pathways or waste-producing procedures such as hydrolysis of nitriles or two-step techniques based on hydroformylation of olefins with highly toxic carbon monoxide with expensive noble catalysts (Rh) followed by oxidation. Unlike hydroformylation methods, OLE-DIOX offers the opportunity of promoting a carboxylation event using unactivated olefins, products produced in bulk from petroleum processing, with abundant carbon dioxide as C1 source. The protocol is user-friendly, with components that are neither air- nor moisture sensitive, utilizes earth-abundant catalysts and operates under mild conditions. OLE-DIOX represents an important contribution for our circular economy by effectively recycling bulk materials into valuable products in one-step operation. These unique features makes OLE-DIOX technically and economically viable for its implementation at large-scale en route to industrially-valuable carboxylic acids, thus avoiding lengthy and waste-producing protocols in the established oil-to-carboxylic acid process chain.

Mots-clés : carbon dioxide,olefins,chain walking,catalysis,carboxylic acids
Projet ERC : iPS-ChOp-AF (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1988750.0 €

Cardiac arrhythmias are responsible for significant morbidity and mortality. However, the study and treatment of these rhythm disorders have been hampered by the lack of relevant human cardiac tissue models, specifically those reflecting patient/disease-specific abnormalities, by paucity of methods for long-term electrophysiological analysis of the tissue, and by the inability to perform targeted, high-resolution, reversible, and functional perturbations of the system. To address these challenges, we propose to combine human induced pluripotent stem cells (hiPSC) and genome-editing (CRISPR) technologies, developmental biology-inspired differentiating systems that yield chamber-specific heart cells, novel tissue engineering strategies, and emerging concepts from the fields of optogenetics and chemogenetics. The resulting experimental models should represent a paradigm shift in the way we study and treat cardiac arrhythmias. To demonstrate the unique potential of this approach, we plan to focus on atrial fibrillation (AF), the most common arrhythmia. Our specific aims are to: 1. Develop patient/disease-specific hiPSC models of genetic AF and to establish hiPSC differentiation protocols to yield purified atrial cells 2. Utilize the hiPSC-atrial cells and advanced tissue-engineering strategies (hydrogels, 3D printing, decellularization) to establish 2D cell-sheet and 3D tissue models of acquired and inherited AF, in which functional re-entry ("rotors") can be studied 3. Utilize tools from optogenetics (light-sensitive ion channels and pumps) or chemogenetics (ligand-specific engineered receptors) for targeted manipulation of the system, to gain insights into AF pathogenesis and to develop novel therapies 4. Evaluate the developed optogenetic and chemogenetic treatments in animal models of AF The results of this project should provide novel mechanistic insights into AF (and other arrhythmias) and open the road for the development of novel therapeutic paradigms.

Mots-clés : cardiac arrhythmias,atrial fibrillation,optogenetics,chemogenetics,induced pluripotent stem cells,tissue engineering
Projet ERC : Mini-HEART (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Leiden University Medical Center — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : LUMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 500000.0 €

Cardiac disease causes morbidity and mortality as frequently as cancer. Predicting cardiac arrhythmia and cardiac failure, understanding multicellular (patho)physiological mechanisms, and devising new treatments represent unmet needs in the field. Human induced pluripotent stem cells (hiPSC) could revolutionise the way we study human disease but unfortunately, they still fall short in recapitulating variable phenotypes and complex cardiovascular diseases. This is partly due to functional immaturity of hiPSC-derived cardiac tissues, shortage of methods for accurate functional analysis and inability to identify cell-type specific contributions to disease pathology. I will address these challenges in Mini-HEART. We recently assembled novel three-dimensional multi-cellular cardiac microtissues as an important step towards full maturation and used these to demonstrate that cardiac disease mutations might directly affect non-myocyte cardiac cells. However, application of hiPSC microtissues to precision medicine remains to emerge. Using a multidisciplinary approach, I will combine isogenic hiPSC, their differentiation into distinct cell types of the heart, multifaceted biophysical assays, and tissue engineering to prove cell-type causality of disease and identify new molecules targeting the culprit cells to rescue the disease phenotype. I plan to use our unique complex hiPSC-cardiac microtissue to 1) identify and synthetically enhance maturation mechanisms; 2) reveal late arrhythmic and fibrotic phenotypes; 3) dissect cell-type specific contributions to complex cardiac diseases, including the role of macrophages and sympathetic nerves; 4) test two therapeutic strategies based on drug-tailoring and gene editing, to modulate the disease phenotype. Together, Mini-HEART will create new opportunities for designing novel biomedical tools to i) capture phenotypic changes, ii) reveal (patho)physiological mechanisms and ii) develop new therapeutic approaches for heart disease.

Mots-clés : cardiac arrhythmia,sudden death,human induced pluripotent stem cells,cardiac organoids,channelopathies,cardiomyopathies
Projet ERC : ECSTATIC (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Université de Bordeaux — Pays : France — Rôle : PI
Acronyme de l'entité : UBx
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1051758.75 €

Cardiac electrical diseases are directly responsible for sudden cardiac death, heart failure and stroke. They result from a complex interplay between myocardial electrical activation and structural heterogeneity. Current diagnostic strategy based on separate electrocardiographic and imaging assessment is unable to grasp both these aspects. Improvements in personalised diagnostics are urgently needed as existing curative or preventive therapies (catheter ablation, multisite pacing, and implantable defibrillators) cannot be offered until patients are correctly recognised. My aim is to achieve a major advance in the way cardiac electrical diseases are characterised and thus diagnosed and treated, through the development of a novel non-invasive modality (Electrostructural Tomography), combining magnetic resonance imaging (MRI) and non-invasive cardiac mapping (NIM) technologies. The approach will consist of: (1) hybridising NIM and MRI technologies to enable the joint acquisition of magnetic resonance images of the heart and torso and of a large array of body surface potentials within a single environment; (2) personalising the inverse problem of electrocardiography based on MRI characteristics within the heart and torso, to enable accurate reconstruction of cardiac electrophysiological maps from body surface potentials within the 3D cardiac tissue; and (3) developing a novel disease characterisation framework based on registered non-invasive imaging and electrophysiological data, and propose novel diagnostic and prognostic markers. This project will dramatically impact the tailored management of cardiac electrical disorders, with applications for diagnosis, risk stratification/patient selection and guidance of pacing and catheter ablation therapies. It will bridge two medical fields (cardiac electrophysiology and imaging), thereby creating a new research area and a novel semiology with the potential to modify the existing classification of cardiac electrical diseases.

Mots-clés : cardiac electrical disorders,magnetic resonance imaging,non invasive electrophysiological cardiac mapping,personalized diagnostics
Projet ERC : ECSTATIC (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Centre hospitalier universitaire de Bordeaux — Pays : France — Rôle : Partner
Acronyme de l'entité : CHU Bordeaux
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 134491.25 €

Cardiac electrical diseases are directly responsible for sudden cardiac death, heart failure and stroke. They result from a complex interplay between myocardial electrical activation and structural heterogeneity. Current diagnostic strategy based on separate electrocardiographic and imaging assessment is unable to grasp both these aspects. Improvements in personalised diagnostics are urgently needed as existing curative or preventive therapies (catheter ablation, multisite pacing, and implantable defibrillators) cannot be offered until patients are correctly recognised. My aim is to achieve a major advance in the way cardiac electrical diseases are characterised and thus diagnosed and treated, through the development of a novel non-invasive modality (Electrostructural Tomography), combining magnetic resonance imaging (MRI) and non-invasive cardiac mapping (NIM) technologies. The approach will consist of: (1) hybridising NIM and MRI technologies to enable the joint acquisition of magnetic resonance images of the heart and torso and of a large array of body surface potentials within a single environment; (2) personalising the inverse problem of electrocardiography based on MRI characteristics within the heart and torso, to enable accurate reconstruction of cardiac electrophysiological maps from body surface potentials within the 3D cardiac tissue; and (3) developing a novel disease characterisation framework based on registered non-invasive imaging and electrophysiological data, and propose novel diagnostic and prognostic markers. This project will dramatically impact the tailored management of cardiac electrical disorders, with applications for diagnosis, risk stratification/patient selection and guidance of pacing and catheter ablation therapies. It will bridge two medical fields (cardiac electrophysiology and imaging), thereby creating a new research area and a novel semiology with the potential to modify the existing classification of cardiac electrical diseases.

Mots-clés : cardiac electrical disorders,magnetic resonance imaging,non invasive electrophysiological cardiac mapping,personalized diagnostics
Projet ERC : HEART.FM (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : CNRS Innovation — Pays : France — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 8285.0 €

Cardiovascular disease is the world’s leading cause of death, and hypertension is its foremost medical risk factor. Reducing blood pressure in hypertensive patients has positive cardiovascular effects, and music listening offers non-pharmacological ways to regulate heart rate and blood pressure. Presently, the most effective way to administer music inventions with long-lasting effects is labor-intensive and relies on professional therapists’ intuitions, making it non-scalable to large cohorts. HEART.FM is an app-creation initiative to democratize access to personalized music medicine interventions, informed by physiological feedback. Current music therapy apps fail to address the subjectivity and specificity inherent in individual music response; a gap further exists between music therapy apps and physiological feedback. By leveraging advances in wearable ECG monitors and portable blood pressure sensors, HEART.FM will offer music therapy based on individual users’ physiological feedback around musical change points and transitions, which correspond to emotionally salient moments in music listening. HEART.FM exploits the music structure knowledge and cross-modal music-physiology analysis methods developed and trialed in the ERC project COSMOS to advance the state of the art by linking physiological feedback with computational music structure analysis to provide personalized music listening therapy to achieve targeted autonomic nervous system responses. A development goal will be to make HEART.FM ready for large-scale deployment in randomized, controlled research trials that can establish music-hypertension cause-effect relationships for healthy individuals as well as hypertensive patients. HEART.FM will benefit the research community by offering a crowdsourced portal for collecting research data in cardiovascular disease and music-based preventative therapies. The PoC will explore commercialization and market solutions in both music and medical sectors.

Mots-clés : personalized music medicine,computational music structure analysis,software system,hypertensive heart disease
Projet ERC : RITA-MI (Horizon 2020, appel 2015, 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 : 15266.0 €

Cardiovascular diseases (CVD) represent a major cause of morbidity and mortality. The best current therapy reduces CV risk by only 25-30% and remains ineffective in reducing the excess risk associated with several co-morbidities. Therefore, there is considerable need for new therapies to limit the burden of CVD. Based on a current ERC Starting Grant project, the applicant’s group proposed and validated the concept that mature B lymphocytes are instrumental in the orchestration of the inflammatory response after ischemic myocardial injury, in part through production of CCL7 chemokine and mobilisation/recruitment of inflammatory monocytes to the infarction site (Zouggari Y et al., Nat Med 2013). Our goal now is to translate this ground-breaking discovery and novel therapeutic concept into benefit for patients. The overall objective of the RITA-MI project is to develop a new and cost-effective therapy for patients with acute myocardial infarction (MI) based on selective targeting of the B cell immune response, with the ultimate aim to substantially reduce the high risk of death and major cardiovascular events associated with the disease. Interestingly, the drug, CD20 monoclonal antibody (mAb) rituximab, is readily available for testing in a re-purposing scheme, allowing for rapid initiation of this proof-of-concept clinical trial. Working Hypothesis: A single infusion of rituximab at the acute phase of MI is safe, substantially depletes circulating B cells, and has the potential to limit infarction size and improves myocardial heart function. Overall objective: Does a ‘fire and forget’ approach with rituximab (a single intravenous infusion) reduce infarct size and/or improve heart function in patients with acute STEMI? The overall aim will be pursued through a series of specific objectives, which will correspond to a first step of a dose-finding proof-of-concept study (the present RITA-MI project), followed (if successful) by a phase II clinical efficacy trial.

Mots-clés : myocardial infarction,lymphocytes,rituximab
Projet ERC : ForceMorph (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Åbo Akademi University — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1037012.5 €

Cardiovascular diseases represent the principal worldwide medical challenge of the 21st century (WHO), and new concepts to treat, predict and even prevent these diseases are needed. Structural remodelling of the vasculature in response to changes in blood flow is important to maintain mechanical homeostasis, and many diseases are related to defects in tissue morphology and mechanical imbalance. Signalling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via the Notch pathway regulates the morphology and structural remodelling of the arterial wall. Importantly, Notch offers handles for therapeutic control and thus opportunities for treatment of malformation and adaptation. However, we lack the essential understanding of how hemodynamic forces integrate with Notch signalling to rationally and responsibly target Notch in vascular therapies. The complexity of the problem requires new tools and an interdisciplinary approach. Our project integrates engineering, computational modelling, with cell biology and in vivo model systems to address the question. In vivo models will validate the in in vitro model systems to ensure that they are reproducible and reflect the reality. Through this integrated approach we will enable new therapeutic developments. The specific objectives of the project are to: 1) Study EC-VSMC signalling real time, at high resolution by a novel biomimetic 4D Artery-on-Chip that recapitulates the cell-composition, -organisation and hemodynamic forces of the physiological artery 2) Develop a computational model of the arterial wall that include the mechanosensitivity of Notch signalling to predict how the complex interactions affect arterial morphology and remodelling 3) Use in vivo animal models to elucidate how regulation of Notch signalling affects tissue morphology and remodelling in response to changes in hemodynamic conditions

Mots-clés : cell signalling,microtissue engineering,computational modelling,vascular morphology
Projet ERC : ForceMorph (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Eindhoven University of Technology — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : TU/e
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 882586.5 €

Cardiovascular diseases represent the principal worldwide medical challenge of the 21st century (WHO), and new concepts to treat, predict and even prevent these diseases are needed. Structural remodelling of the vasculature in response to changes in blood flow is important to maintain mechanical homeostasis, and many diseases are related to defects in tissue morphology and mechanical imbalance. Signalling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via the Notch pathway regulates the morphology and structural remodelling of the arterial wall. Importantly, Notch offers handles for therapeutic control and thus opportunities for treatment of malformation and adaptation. However, we lack the essential understanding of how hemodynamic forces integrate with Notch signalling to rationally and responsibly target Notch in vascular therapies. The complexity of the problem requires new tools and an interdisciplinary approach. Our project integrates engineering, computational modelling, with cell biology and in vivo model systems to address the question. In vivo models will validate the in in vitro model systems to ensure that they are reproducible and reflect the reality. Through this integrated approach we will enable new therapeutic developments. The specific objectives of the project are to: 1) Study EC-VSMC signalling real time, at high resolution by a novel biomimetic 4D Artery-on-Chip that recapitulates the cell-composition, -organisation and hemodynamic forces of the physiological artery 2) Develop a computational model of the arterial wall that include the mechanosensitivity of Notch signalling to predict how the complex interactions affect arterial morphology and remodelling 3) Use in vivo animal models to elucidate how regulation of Notch signalling affects tissue morphology and remodelling in response to changes in hemodynamic conditions

Mots-clés : cell signalling,microtissue engineering,computational modelling,vascular morphology
Projet ERC : NECROPTOSIS (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Cologne — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Cell death plays an important role in host defence particularly in response to virus infections, but also contributes to tissue damage, inflammation and disease. Therefore, dissecting the mechanisms regulating cell death and its function in immunity and inflammation will be important for the better understanding of the pathogenesis of infectious and inflammatory diseases. Necroptosis is a recently characterised type of regulated necrotic cell death induced by RIPK3 and its substrate MLKL. Necroptosis has been implicated in host defence as well as in the pathogenesis of a number of inflammatory disorders, however the mechanisms regulating necroptosis in vivo as well as its functional implications in health and disease remain poorly understood. Recent studies revealed that ZBP1/DAI, a protein that senses Z-nucleic acids and activates RIPK3-induced cell death, regulates anti-viral immunity, tissue homeostasis and inflammation, suggesting that necroptosis is an important mechanism of Z-DNA/RNA-induced immune responses. However, the mechanisms regulating the detection of Z-nucleic acids as well as the activation of downstream signalling to cell death and inflammation by ZBP1 remain elusive. Necroptosis is also induced downstream of cytoplasmic nucleic acid sensors that trigger interferon responses and are implicated in anti-viral immunity, inflammation and autoimmunity. Therefore, necroptosis triggered directly or indirectly by nucleic acid sensors may have a broad role in nucleic acid-induced immune responses. Here we propose to study the mechanisms of regulation as well as the functional role of necroptosis induced downstream of nucleic acid-sensing receptors in immunity, inflammation and autoimmunity. These studies aim to advance our understanding of the role of cell death in immunity and inflammation and to reveal novel paradigms in the pathogenesis of infectious and inflammatory diseases.

Mots-clés : cell death,necroptosis