Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : rEnDOx (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Turin — Pays : Italie — Rôle : Partner
Acronyme de l'entité : UNITO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 303752.46 €

Endothelial cells (ECs) exhibit a remarkable and unique plasticity in terms of redox biology and metabolism. They can quickly adapt to oxygen, nitric oxide and metabolic variations. Therefore, EC must be equipped with a selective and unique repertoire of redox and metabolic mechanisms, that play a crucial role to preserve redox balance, and adjust metabolic conditions in both normal and pathological angiogenesis. The identification of such redox signaling and metabolic pathways is crucial to the gaining of better insights in endothelial biology and dysfunction. More importantly, these insights could be used to establish innovative therapeutic approaches for the treatment of those conditions where aberrant or excessive angiogenesis is the underlying cause of the disease itself. However, the formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. Here, by using cutting-edge real-time redox imaging platforms, and innovative molecular and genetic approaches in different in vivo animal models, we will (1) reveal the working of redox signaling in EC in health and disease, (2) shed light on the novel role for the mevalonate metabolic pathway in angiogenesis and (3) provide solid evidence, that manipulation of endothelial redox and metabolic state by genetic alteration of the redox rheostat UBIAD1, is a valuable strategy by which to block pathological angiogenesis in vivo. The ultimate objective is to open the way for the development of innovative (cancer) therapeutic strategies and complement the existing ones based on genetic or pharmacological manipulation of redox rheostats to balance oxidative or reductive stress in angiogenic processes. The success of this project is built upon our major expertise in the field of angiogenesis in small vertebrate animal models as well as on the collaborations with leading laboratories that are active in research on the pre-clinical stages for angiogenesis-rel

Mots-clés : redox signaling,zebrafish model,tumor angiogenesis
Projet ERC : MODVASC (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Heidelberg University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 65477.5 €

Endothelial cells cover the entire arterial and venous tree, and play a pivotal role in vascular and organ homeostasis. In general, cardiovascular risk factors induce endothelial cell activation towards a pro-inflammatory phenotype leading to atherosclerosis, a major cause of mortality in the Western world. Understanding the mechanisms that orchestrate endothelial cell functions and response to environmental stimuli is essential for the discovery and development of novel biomarkers and therapeutic strategies in vascular disease. RNA base modifications increase the RNA alphabet from the 4 canonical nucleotides to more than 140. Adenosine methylation at the N6 position (m6A) is the most prevalent RNA modification in eukaryotic mRNA and is catalyzed by a multiprotein methyltransferase complex. Accumulating recent evidence suggests that m6A RNA methylation is a critical posttranscriptional regulator of RNA metabolism. In preliminary unpublished work we have identified methylated RNA targets, which may critically regulate endothelial cell functions. Since the impact of m6A RNA methylation on vascular function is completely unknown, MODVASC aims to explore the role of m6A RNA methylation in vascular growth, homeostasis and disease. By m6A-RNA immunoprecipitation followed by RNA-sequencing we will identify the transcriptome-wide m6A RNA methylation in endothelial cells under basal and stress conditions. With the help of advanced molecular biology and biochemical methods, we will describe in single nucleotide level the impact of m6A RNA methylation on mRNA fate and RNA-protein interactions and define its functional consequences in endothelial cell functions. In vivo studies will consolidate the impact of endothelial RNA methylation on vascular growth and homeostasis as well as its contribution to atherosclerosis. Finally, MODVASC will evaluate the clinical relevance of our findings in patients with cardiovascular disease.

Mots-clés : endothelial cells,mrna stability,rna modifications,vascular barrier function,vascular disease,atherosclerosis
Projet ERC : PostTransGC (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Enduring protection from pathogens and robust responses to vaccination depend on the generation of high-affinity antibodies through the germinal center (GC) reaction. In GCs, T helper cells promote the extensive proliferation of high-affinity B cell clones and their differentiation into plasma cells through cellular interactions that modulate gene expression. Here, we aim to unravel multiple post-gene expression mechanisms, including mRNA and protein stability regulation, that jointly control the outcome of T-B interactions in GCs. Since it is technically challenging to examine gene transcription and cellular contacts simultaneously, a method that links these two processes and measures transcription in-situ is required. To understand how T cell help controls gene expression dynamics and persistence of mRNA transcripts in GC B cells, we will use LN-smFISH, a new method we recently developed that combines imaging of individual cells and single mRNA transcripts within lymph nodes. Through in-vivo manipulation of B cells and co-visualization of single cells and mRNAs, we will define the dynamics of gene expression during T-B contacts and plasma cell generation in GCs (Aim1). Using our specialized in-vivo models, we will examine how modulation of mRNA stability and translation by transcript methylation controls B cell clonal expansion and define which genes are regulated by this machinery (Aim2). Finally, we will examine how the degradation of known and novel key proteins control gene networks and B cell fate in GCs (Aim3). Together, we envision the establishment of a unifying model for how sequential layers of regulation orchestrate the translation of T-B interactions to fate decisions. The findings may lead to improved vaccine strategies and expose new checkpoints for manipulation in autoimmune diseases and GC-derived lymphoma. On a broader scale, we expect to define new concepts about the role of mRNA and protein stability machineries under physiological conditions.

Mots-clés : germinal centers,b cells,antibodies,lymphocytes,immune cell interactions
Projet ERC : MetalFuel (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Eindhoven University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU/e
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2492992.0 €

Energy-on-demand is a cornerstone of modern society. Currently, the primary source of energy is fossil fuel, but in view of undeniable climate warming, an alternative fuel is dearly wanted. Metal powders are a tantalizing, totally carbon-free and recyclable option for such a fuel. Its combustion products are solid metal-oxide particles, which, after capture, can be recycled to metal powders again using green electricity. The technology required to burn metal powder aerosols in a stable and reliable way is, however, still in its infancy. Rapid growth of the technology is unlikely, because fundamental understanding of combustion of dense metal aerosols is largely lacking. Herein lies a virgin field of fundamental research, with huge potential for practical application. Fundamental principles behind metal fuel flames are addressed in this proposal, in a step-wise, combined experimental & theoretical/numerical approach. On single-particle level, I will unravel the influence of mutual interactions. Their consecutive ignition will create combustion wave fronts traveling through metal aerosols. Such planar flame fronts will be created in the lab as well as studied numerically and subsequently used as building block for modeling 3D flames. Finally, Bunsen-type burners will be developed to characterize turbulent, 3D flames. Detailed experiments using microscopy for metal-(oxide) particle composition as well as new optical diagnostic techniques on dedicated, lab-scale metal aerosol burners will serve as benchmarks for validation of models. I have a 30 years track record in theoretical, numerical & experimental combustion research, focusing on fundamental aspects of combustion processes relevant to practical applications. In this project this experience will be the foundation from which to explore a new direction in fundamental combustion research. This METALFUEL project will boost to a new branch of combustion research, with the potential for disruptive applications.

Mots-clés : metal fuels,carbon free,energy on demand,multi scale modeling,prototype burners,microparticles,heatflux,flamelet generated manifolds
Projet ERC : VascArbor (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Twente — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Engineered tissues offer a great promise to the field of medicine as an alternative for donor tissues, for which the supply is not meeting the demands. However, the clinical application of engineered tissues is hampered. The integration of engineered tissues after implantation is limited due to the lack of a vascular network. Currently, strategies to include vascular networks rely on the spontaneous organization of vascular cells, or on the patterning of these cells. However, this results in either vascular networks that are not organized, or networks that lose their initial organization fast. This project will use a unique and novel approach to control vascular development and will therefore result in a vascular network with a controllable long-term organization. By allowing for anastomosis, and increasing nutrient delivery, this project will tackle an essential problem and will greatly enhance the clinical applicability of engineered tissues. Within VascArbor, fluid flows through engineered tissues will be designed and controlled to guide vascular organization. Apart from that, growth factors will be patterned in space and time to further direct the formation of a vascular network with a controlled organization. In parallel, computational models will be developed that can predict vascular organization and development based on processing parameters. This will be a breakthrough in vascularized tissue engineering by enabling a direct link between a desired vascular organization, and the tissue construct geometry and processing conditions that are needed to acquire this organization. To maximize the impact of VascArbor on the field of tissue engineering and medicine, the principles that will guide vascular organization are compatible with multiple current and future tissue fabrication technologies. Within VascArbor, tissue building blocks and bio-printing will be used to engineer vascularized cardiac muscle tissue based on the principles developed in this project.

Mots-clés : tissue engineering,vascularization,fluid flow,growth factor,endothelial cell
Projet ERC : MYCOCHASSIS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Centre for Genomic Regulation — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG;CRG-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 2454522.0 €

Engineering bacteria to deliver therapeutic agents or to present antigens for vaccination is an emerging area of research with great clinical potential. The most challenging issue in this field is the selection of the right bacteria to engineer, commonly known as “chassis”. The best chassis depends on the application but there is a common drawback in bacteria used nowadays: their complexity and the lack of quantitative information for many reactions which limits genome engineering to classical trial and error approaches. In this project, we want to engineer the genome-reduced bacterium M. pneumoniae using a whole-cell model that will drive the rational to create a chassis for human and animal therapy. Its small size (816 Kbases), the lack of cell wall, and the vast amount of comprehensive quantitative –omics datasets makes this bacterium one of the best candidates for chassis design. By combining bioinformatics, -omics, and biochemistry approaches with genome engineering tools, systems biology analyses, and computational whole-cell models, MYCOCHASSIS aims to: i) develop a whole cell-model based on organism-specific experimental data that will be validated experimentally and that can predict the impact of genome modifications; ii) implement genome engineering tools to delete non-essential pathogenic and virulent elements predicted by the whole-cell model to engineer a therapeutical chassis; iii) using the whole-cell model design and engineer genes and circuits to improve growth rate in a defined medium. iv) as a proof of concept introduce orthogonal gene circuits to secrete peptides and enzymes capable of dissolving in vitro biofilms made by the lung pathogens Pseudomonas aeruginosa and Staphylococus aureus. This project will validate the usefulness of whole-cell models for synthetic biology by modelling multiple genomic modifications orientated to facilitate engineering of biological systems.

Mots-clés : minimal cell,therapeutic chassis
Projet ERC : SE3DPASTE (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Twente — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Engineering tissues with a hierarchical vascular network, which is the goal of our ERC project VascArbor, is challenging. Developments in the field of biofabrication, including 3D bioprinting, are promising to cope with this challenge. However, current strategies lack the capacity to create hierarchical, high resolution, cost efficient, upscalable constructs in a standardized manner with a single approach. Embedded bioprinting, allowing the deposition of complex constructs without the need of a supporting substrate, provides a potential solution. However, embedding baths used so far consist of inert materials and therefore cannot become a functional component of the tissue. Also, the embedding bath should be patternable to allow for multistructural tissues, but printing of the bath itself is currently challenging due to clogging of the nozzle. SE3DPASTE will develop a dehydrated precursor of a free standing embedding bath that is storable for “off-the-shelf” use and tissue specific. Additionally, SE3DPASTE will develop a bespoke 3D printing nozzle that will allow for the creation of patterned embedding baths. SE3DPASTE will lead to storable, transportable, tissue specific embedding baths that act as a patterning template and can be used for embedded bioprinting of tissue. This combination of features, which does currently not exist in embedding baths for 3D printing, will be a key enabler for the generation of standardized 3D tissue environments that lead to predictable tissue development for research-, clinical-, or drug screening purposes. SE3DPASTE will not only develop the technology to make this possible, but will also take vital steps to bring this technology to the market. By securing the IP, and analyzing the market and the willingness of investors to support SE3DPASTE technology, a fruitful basis for translation will be formed. Finally, this will lead to a business plan providing a roadmap on the necessary future steps to create a market ready product.

Mots-clés : 3d bioprinting,suspension printing,dehydration,rehydration,nozzle,multistructural tissue,vascularization
Projet ERC : SCORA (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : McGill University — Pays : Canada — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 60352.5 €

Enhancers control the correct spatio-temporal activation of gene expression. A comprehensive characterization of the properties and regulatory activities of enhancers as well as their target genes is therefore crucial to understand the regulation and dysregulation of differentiation, homeostasis and cell type specificity. Genome-wide chromatin assays have provided insight into the properties and complex architectures by which enhancers regulate genes, but the understanding of their mechanisms is fragmented and their regulatory targets are mostly unknown. Several factors may confound the inference and interpretation of regulatory enhancer activity. There are likely many kinds of regulatory architectures with distinct levels of output and flexibility. Despite this, most state-of-the-art genome-wide studies only consider a single model. In addition, chromatin-based analysis alone does not provide clear insight into function or activity. This project aims to systematically characterize enhancer architectures and delineate what determines their: (1) restricted spatio-temporal activity; (2) robustness to regulatory genetic variation; and (3) dynamic activities over time. My work has shown enhancer transcription to be the most accurate classifier of enhancer activity to date. This data permits unprecedented modeling of regulatory architectures via enhancer-promoter co-expression linking. Careful computational analysis of such data from appropriate experimental systems has a great potential for distinguishing the different modes of regulation and their functional impact. The outcomes have great potential for providing us with new insights into mechanisms of transcriptional regulation. The results will be particularly relevant to interpretation of regulatory genetic variations. Ultimately, knowing the characteristics and conformations of enhancer architectures will increase our ability to link variation in non-coding DNA to phenotypic outcomes like disease susceptibility.

Mots-clés : transcriptional regulation,enhancers,enhancer rna
Projet ERC : Financing_Entrep (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1590330.0 €

Entrepreneurship is widely accepted as a key driver of economic growth and is a central policy priority across the world, including in the EU through initiatives such as the EU’s Entrepreneurship 2020 Action Plan. While access to capital is viewed as one of the biggest hurdles to starting and growing a new business, the manner in which financing constraints for startups are invoked in academic work and policy frameworks is often poorly fleshed out. This lack of clarity is also reflected in the way policy makers sometimes invoke images of Silicon-Valley-type venture capital (VC) backed entrepreneurship when proposing reforms that are tailored towards small businesses with low growth potential. My ERC CoG project aims to quantify and address financing frictions facing ‘high potential entrepreneurship’ through three related areas of inquiry: 1. Characterizing the financing sources and constraints facing high-potential entrepreneurs and small and medium sized enterprises (SMEs) that are responsible for driving employment and productivity growth in the economy. 2. Developing adaptations to venture capital’s funding model to overcome specific financing hurdles facing the translation and scale-up of science-based ‘tough tech’ ventures. 3. Understanding the dynamics of agglomeration in emerging industries, with a particular focus on how capital markets policy can impact where clusters of frontier technologies emerge.

Mots-clés : entrepreneurial finance,venture capital
Projet ERC : HEAL (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of Mannheim — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UMA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1420365.0 €

Environmental quality has been improving dramatically in Europe, helped by structural transformation and by environmental regulation. Notwithstanding such improvements, environmental regulation continues to be a top priority for policy makers in Europe and other post-industrial societies. Global climate change is an important reason for this. Increasing demand for environmental quality is another one, explaining why some of the richest agglomerations in Europe have been adopting very costly measures to further reduce air pollution. Both global climate change and regional air pollution originate to a large extent from the combustion of fossil fuels, an activity that, in Europe, is costly to curb but also causes substantial damage to human health. This project contributes new tools for assessing this trade-off by (i) developing empirical models that greatly enhance spatial detail in state-of-the-art economic impact analysis, (ii) pioneering an interdisciplinary approach that links causal inference on pollution emissions at the source to chemical transport models for air pollutants, and (iii) incorporating subclinical and long-term health impacts of air pollution into economic damage estimates. Part I of the project studies the economic implications of changes in local air quality that were an unintended consequence of the European Union Emissions Trading Scheme for carbon dioxide. Part II analyzes the impacts of air pollution on labor supply, health, and migration in a unified empirical framework. The key objective of this project is to provide empirical evidence that can inform environmental policy-making in the broad contexts of climate policy and air quality management. Given the ambitious concepts proposed, the global significance of the environmental problems addressed, and the focus on policy, this project has the potential to make a large impact.

Mots-clés : climate policy,emissions trading,cost benefit analysis,integrated assessment,air pollution,program evaluation,sickness insurance,moral hazard,valuation of health impacts