Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : 5D Heart Patch (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : PI
Acronyme de l'entité : KI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2149227.5 €

Developing new therapeutic strategies for heart regeneration is a major goal for cardiac biology and medicine. While cardiomyocytes can be generated from human pluripotent stem (hPSC) cells in vitro, it has proven difficult to use these cells to generate a large scale, mature human heart ventricular muscle graft on the injured heart in vivo. The central objective of this proposal is to optimize the generation of a large-scale pure, fully functional human ventricular muscle patch in vivo through the self-assembly of purified human ventricular progenitors and the localized expression of defined paracrine factors that drive their expansion, differentiation, vascularization, matrix formation, and maturation. Recently, we have found that purified hPSC-derived ventricular progenitors (HVPs) can self-assemble in vivo on the epicardial surface into a 3D vascularized, and functional ventricular patch with its own extracellular matrix via a cell autonomous pathway. A two-step protocol and FACS purification of HVP receptors can generate billions of pure HVPs- The current proposal will lead to the identification of defined paracrine pathways to enhance the survival, grafting/implantation, expansion, differentiation, matrix formation, vascularization and maturation of the graft in vivo. We will captalize on our unique HVP system and our novel modRNA technology to deliver therapeutic strategies by using the in vivo human ventricular muscle to model in vivo arrhythmogenic cardiomyopathy, and optimize the ability of the graft to compensate for the massive loss of functional muscle during ischemic cardiomyopathy and post-myocardial infarction. The studies will lead to new in vivo chimeric models of human cardiac disease and an experimental paradigm to optimize organ-on-organ cardiac tissue engineers of an in vivo, functional mature ventricular patch for cardiomyopathy
Projet ERC : METAPTPs (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Université Libre de Bruxelles — Pays : Belgique — Rôle : PI
Acronyme de l'entité : ULB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1966906.0 €

Diabetes mellitus is characterised by hyperglycaemia caused by an absolute or relative insulin deficiency. The global prevalence of diabetes has reached more than 410 million individuals, underscoring the need for novel therapeutic strategies targeting the pathology as a multi-organ disease. Protein tyrosine phosphatases (PTPs) constitute a superfamily of enzymes that dephosphorylate tyrosine-phosphorylated proteins and oppose the actions of protein tyrosine kinases. My previous studies and preliminary data suggest that PTPs act as molecular switches for key signalling events in the development of diabetes, i.e. insulin/glucose/cytokine signalling. Dysregulation of these pathways results in metabolic consequences that are cell-specific. Oxidative stress abrogates the nucleophilic properties of the PTP active site and induces conformational changes that inhibit PTP activity and prevent substrate-binding. I have recently developed an innovative proteomic approach to quantify PTP oxidation in vivo and demonstrated that this occurs in liver/pancreas under pathological conditions, including obesity and inflammation. In this proposal, I aim to fully characterise the activity and oxidation status of PTPs in dysfunctional metabolic relevant cells in obesity and diabetes. Importantly, the crucial role of PTPs make them promising candidates for the treatment of metabolic disorders. I hypothesise that specific antioxidants, diets and/or adenovirus will restore PTP function and ameliorate the metabolic deleterious defects in pre-clinical studies. Over the next 5 years, I aim to: • Identify the major oxidised PTPs in metabolic relevant tissues/cells in both obesity and diabetes. • Determine the contribution of PTP inactivation in cellular responses to metabolic signalling in human samples. • Assess the impact of tissue-specific PTP deficiency on the development of obesity and diabetes. • Test novel therapeutic approaches targeting PTPs to prevent/reverse metabolic disorders.

Mots-clés : protein tyrosine phosphatases,diabetes,insulin signalling
Projet ERC : AI-PREVENT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 1550057.0 €

Diabetes, stroke and coronary artery disease (cardiometabolic diseases) are the leading cause of death in Europe. Given that effective pharmacological and lifestyle interventions are available, it is important to identify high risk individuals at an early stage. Traditionally, this is done using clinical prediction models. However, the established models have substantial limitations: they are often used by doctors only when an underlying disease is already suspected, they are not developed on updated nationally-representative data and they require time-consuming clinical measurements. Thus, a substantial part of the population is not provided with risk assessment. I propose to revolutionize the existing approaches to primary prevention by providing risk assessment of cardiometabolic diseases before an individual even steps into the doctor’s office for a visit. To this end my project has three main objectives: 1) Development of artificial intelligence (AI) approaches to model health trajectories based on nationwide registry data on medications, diagnoses, familial risk and socio-demographic information to obtain accurate risk estimates for cardiometabolic disease. I will integrate high quality data from selected countries that have long traditions of registry data (Finland and Sweden, over 7.5 million individuals). 2) To identify health trajectories that maximize the clinical utility of genetic scores by integrating genetic and registry-based data on > 1 million people to identify subgroups of individuals for whom genetic information might improve risk prediction. 3) Validation of AI and genetic-based risk assessment as first-stage screening via a clinical study in 2800 individuals. My project leverages the latest developments in AI and high-quality data of unprecedented scale to deliver a paradigm shift with important public health consequences by potentially changing the way cardiometabolic disease risk is assessed.
Projet ERC : RadioClick (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 62500.0 €

Diagnosing cancer as early as possible is one of the most powerful strategies in modern medicine to improve human well-being. Antibodies (Abs) are excellent molecules that can be used to target specific tumors. As Abs require hours to days for accumulating on tumor surfaces, the use of Abs for nuclear imaging (such as PET imaging) is limited by the short half-lives of popular radioisotopes. Therefore, we plan to move the step of radiolabeling from the bench to the tumor itself. However, the entanglement of Abs with an artificial chemical probe is one of the most promising but at the same time one of the most technically challenging developmental areas in biotechnology. Our unique approach is based on the production of “hybrid-Abs”, which combine in only one “click” step the power of synthetic chemistry with the best of biology (“custom-biologics”). Our unique selling points are ultra-fast, exceptional bioorthogonal and specific labeling reactions in living organism as well as a both-sided modularity of the connection between Abs and chemical probe. By doing so, high contrast visualization of the cancer will become possible.

Mots-clés : noncanonical amino acid,labeling,radiomarker,site specific,click chemistry,tetrazine
Projet ERC : iMDx (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : KTH Royal Institute of Technology — Pays : Suède — Rôle : PI
Acronyme de l'entité : KTH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499180.0 €

Diagnosis of an increasing number of diseases (such as HIV, Ebola and antibiotic resistant bacteria) rely on centralized laboratories with specialized instruments and skilled personnel. This type of clinical analysis with long lead times and high cost is inappropriate for point of care diagnostics. Portable, automated, and disposable devices with integrated molecular diagnostics (iMDx), could solve this problem. Such devices, however, basically do not exist today. This research program will develop materials, methods, and diagnostic techniques to enable portable integrated molecular diagnostics (iMDx) devices, that are disposable (almost zero-cost), and that can detect a broad range of diseases using DNA amplification. To achieve this, we will develop "3D microfiber electrofluidics (MEF)". MEFs rely on simple and readily available porous sheets including paper, and textiles. Their fabrication is simple, and yet they are very powerful because they can monolithically integrate 3D microfluidics, 3D microelectronics, electrochemical analysis, storage of reagents / biomolecules, as well as handling and manipulation of cells. We will develop techniques, using the combined capabilities of MEFs, for real-time DNA amplification and electrochemical DNA detection directly from samples. We will use three amplifications techniques for realizing a comprehensive iMDx platform: i) DNA detection, using established and state of the art amplification methods (e.g. PCR, LAMP, RPA). ii) RNA detection, using "nucleic acid sequence-based amplification" (NASBA). iii) Protein detection, using antibody to DNA translation through "proximity ligation assay" LPA, and using the detection of the amplified DNA is the indirect measure of proteins. The outcome of this program has the potential to be ground breaking, and change the structure of measuring, processing, and pricing of biomedical information, and dramatically broaden its accessibility and applicability.
Projet ERC : RMGPP (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of London — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 80012.0 €

Differences in productivity explain much of differences in income levels across countries, yet little is known about how to improve productivity of manufacturing in the developing world. Recent research reveals very high dispersion in productivity in low-income countries. We examine firm productivity at a uniquely detailed level, collecting sub-factory production and survey data from hundreds of garment manufacturers in several countries. The data, coupled with a new method for comparing productivity, allow us to measure physical productivity in and across firms and among heterogeneous products. Initial results from nearly 100 factories in Bangladesh show significant dispersion of productivity within factories; production lines at the 90th percentile are 50% more efficient than those at the 10th percentile. Differences are highly persistent – puzzling given that the lines are often on the same production floor. Capital and the quality of the buyer explains a small part of the dispersion: lines producing goods for higher-end buyers are significantly more efficient. Shocks and interventions allows us to examine the challenges of increasing productivity in volatile conditions characteristic of low-income countries. Our data span a period including general strikes and a 67% minimum wage increase. We have conducted 2 RCTs on line supervisor training. We are designing data collection and analysis tools for use by factories and a program to address issues related to worker stress. We have collected data from 10 factories in Pakistan to benchmark productivity across countries. We are also working with the garment association in Myanmar. Relationships with large European-based buyers have led to discussions on linking with their suppliers in other countries. Our goal over the next 2 years is to collect data from at least 6 to 8 countries in Asia and Africa allowing cross-country analysis of productivity in lower-income countries at an unprecedented level of detail.

Mots-clés : productivity dispersion,productivity and growth,persistent productivity differences,private sector development,management practices,social compliance
Projet ERC : STRINGENCY (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1494042.0 €

Difficult-to-treat chronic and recurrent bacterial infections are often caused by bacteria that are sensitive to commonly used antibiotics. The reasons for this recalcitrance are frequently unknown. However, when grown in the laboratory, all bacteria, including major pathogens form persister cells that are multidrug tolerant, a phenomenon thought to be a major factor underlying recalcitrant infections. We observed that the general bacterial stress response, known as “the stringent response”, plays a key role in persister cell maintenance. Indeed, stochastic variation of the stringent response regulator ppGpp triggers persister cell formation. However, the molecular mechanisms by which environmental cues activate the stringent response are still largely unknown and represent one of the most fundamental, unsolved problems in prokaryotic molecular biology. Importantly the stringent response is also required for virulence of almost all bacterial pathogens, strongly arguing that novel insights into ppGpp biology will lead to novel methods to combat infections. We recently observed that the ppGpp synthetase II activity encoded by SpoT is responsible for persister cell formation in Escherichia. coli. Therefore, I propose a research program that builds on the pivotal role of SpoT in bacterial persistence, with the goal of dissecting the molecular mechanisms by which environmental stimuli trigger SpoT-dependent ppGpp synthesis. This project has three main objectives: (i) To unravel how spoT expression is regulated (ii) To reveal how ppGpp synthetase II activity is mechanistically controlled and (iii) To decipher the physiological role of SpoT in persister cell decision-making. The program is ambitious and will provide a significant step forward for the persistence field and offer novel, fundamental insights into ppGpp biology. Moreover, it may represent an invaluable resource to improve biotechnological processes and how bacterial infections are treated.

Mots-clés : p ppgpp,stringent response,spot,bacterial persistence,bacterial virulence,multidrug tolerance,bacterial stress response
Projet ERC : DIPVAR (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : European School of Management and Technology — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : ESMT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 943000.0 €

Digital platforms, such as Amazon, Alibaba, Google, have become important global players. Their practices have led to significant anti-trust and regulatory scrutiny, and interventions. The existing theoretical models are not suited for the analysis of most of digital platforms as they fail to capture their important aspects and dynamics. This project’s first goal is to develop tractable and applicable models of markets with digital platforms capturing their unique features. The second goal is to investigate the implications of digital platforms’ business practices on prices, variety and quality provision to buyers, on small rivals, and on potential platform entry. I plan to attain these goals via two work packages: WP1 will provide a tractable framework capturing important characteristics of online market places and can thus be used to analyze e-commerce platforms’ optimal seller contracts and the implied variety offered to consumers. After illustrating an equivalence between a trade platform and a multiproduct monopolist, WP1 will identify with which demand systems and information structure multiproduct firms under-/over-provide variety. Using equivalence conditions WP1 will study whether, how, and when the variety implied by platforms’ pricing diverges from the social optimality and which type of seller contracts could mitigate such distortions. WP2 will provide tractable and applicable models to study competition between asymmetric platforms to attract high quality sellers. WP2 will analyze how platforms’ restrictions on users multi-homing (participating in multiple platforms) and restrictions on switching behavior of users affect market allocation, quality provision, prices, entry and dynamics. The findings of this project will highlight potential distortions in these multi-billion markets and ultimately suggest effective policy recommendations for competition policy in digital markets, which can greatly improve consumer welfare in the EU.

Mots-clés : digital platforms,pricing,variety,quality
Projet ERC : DigiScore (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : De Montfort University — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : DMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 374458.71 €

Digital scores utilising computational technology and digital media are emerging worldwide as the next evolutionary stage in the concept of the music score (Vear 2019). Yet there has been no scientific study of digital scores; nor their effect upon creativity and musicianship. This is remarkable for two reasons: First, because digital scores are generating new music experiences, innovative compositional approaches, novel performance opportunities, and broader accessibility for a vast number of musicians and music cultures around the world. Second, because many topics immediately adjacent or informing digital scores have been theorised thereby liberating these subjects and innovating creative practices, e.g. digital media art, digital performance, electro-acoustic music. This project will launch the first scientific investigation into the transformation of the music score through computational technologies. The core aims of the project are to: (1) determine scientific knowledge of how digital scores stimulate new creative opportunities and experiences within a range of music practices, (2) develop a theoretical framework for digital scores as an important transdisciplinary area of research, (3) build a scientific study of inclusive digital musicianship through the transformative potential of the digital score. This project will investigate these questions through an innovative combination of artistic and scientific research methods, undertaken by a transdisciplinary and international team of scientists and artists, led by a world expert of digital scores: Prof. Dr. Craig Vear. This is real “frontier research”, the benefits of which extend beyond music studies into computer science, new media research, digital humanities, performance studies and creative practice.

Mots-clés : music scores,performance practice,computational technology
Projet ERC : IMAGINE (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2143826.0 €

Direct lineage reprogramming of cell identity in the nervous system offers the prospect of remodelling diseased brain circuits. Recent years have provided evidence for the possibility of converting brain glia into neurons in vivo. Yet, the process by which glial cells give up their original identity and adopt a neuronal fate remains by large enigmatic. Moreover, it is unclear how neurons induced from glia may integrate into the pre-existing circuits of non-neurogenic brain regions such as the cerebral cortex. Finally, can they participate in cortical information processing and even restore dysfunctional cortical circuits? We have discovered a specific cocktail of reprogramming factors that gives rise to induced neurons with hallmark features of fast-spiking, parvalbumin-expressing interneurons, a neuronal subtype that is highly vulnerable in neuropsychiatric and neurological disorders. Here, we aim at visualising the conversion of glia into these induced interneurons in real time by in vivo imaging. This will not only unambiguously demonstrate the genuineness of the identity switch, but also unveil cellular intermediates along the reprogramming process. By measuring single cell gene expression during conversion, we will be able to relate intermediate states to their molecular underpinnings. Moreover, in vivo imaging will allow us to follow structural remodelling of dendrites as induced interneurons integrate into pre-existing cortical circuitry. By using in vivo calcium imaging in primary visual cortex, we will examine whether induced interneurons become recruited into sensory information processing circuits. Finally, we will scrutinise induced interneurons for their ability to rescue excitation-to-inhibition balance in a mouse model of endogenous interneuron dysfunction. IMAGINE will thus break new ground towards unveiling the full potential of engineered neurogenesis for brain repair.

Mots-clés : cell fate,lineage reprogramming,proneural,transcription factor,dendritic remodelling,in vivo calcium imaging