Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : AMADEUS (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1994900.0 €

Carbon dioxide capture and storage is a technology to mitigate climate change by removing CO2 from flue gas streams or the atmosphere and storing it in geological formations. While CO2 removal from natural gas by amine scrubbing is implemented on the large scale, the cost of such process is currently prohibitively expensive. Inexpensive alkali earth metal oxides (MgO and CaO) feature high theoretical CO2 uptakes, but suffer from poor cyclic stability and slow kinetics. Yet, the key objective of recent research on alkali earth metal oxide based CO2 sorbents has been the processing of inexpensive, naturally occurring CO2 sorbents, notably limestone and dolomite, to stabilize their modest CO2 uptake and to establish re-activation methods through engineering approaches. While this research demonstrated a landmark Megawatt (MW) scale viability of the process, our fundamental understanding of the underlying CO2 capture, regeneration and deactivation pathways did not improve. The latter knowledge is, however, vital for the rational design of improved, yet practical CaO and MgO sorbents. Hence this proposal is concerned with obtaining an understanding of the underlying mechanisms that control the ability of an alkali metal oxide to capture a large quantity of CO2 with a high rate, to regenerate and to operate with high cyclic stability. Achieving these aims relies on the ability to fabricate model structures and to characterize in great detail their surface chemistry, morphology, chemical composition and changes therein under reactive conditions. This makes the development of operando and in situ characterization tools an essential prerequisite. Advances in these areas shall allow achieving the overall goal of this project, viz. to formulate a roadmap to fabricate improved CO2 sorbents through their precisely engineered structure, composition and morphology.

Mots-clés : carbon dioxide capture
Projet ERC : ECSTATIC (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Institut national de recherche en sciences et technologies du numérique — Pays : France — Rôle : Partner
Acronyme de l'entité : Inria
Type d'entité : Recherche
Financement ERC de l'entité : 288750.0 €

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 : SIRENE (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Maastricht University — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Cardiac hypertrophy is the principal risk factor for the development of heart failure and lethal arrhythmias. A complex web of interconnected signalling pathways has been implicated in hypertrophy and species of non-coding RNA molecules, microRNAs, have been shown to regulate these pathways. The recognition of microRNAs as potential therapeutic targets marks the principal step towards new therapeutic concepts. The SIRENE project represents the advancement of the therapeutic strength of miRNA silencing in clinically relevant heart failure models towards a valuable proposition for counteracting pathological hypertrophic signalling and heart failure development. In specific, during the related ERC CALMIRS project, it was found that sustained knockdown of endogenous miR-199b in the adult mouse heart in vivo leads to profound protective effects against symptoms of heart failure. Therefore, a new class of RNA antagonists, targeting miRNAs is powerful and holds great promise to become the next generation therapeutics. At this stage the newly developed antagonists are unique in their affinity and specificity for miR-199b and current data demonstrates a profound rescue by miR-199b antagonists on heart failure symptoms such as pressure overload induced cardiac morphological, histological, functional and molecular abnormalities in mice. The challenge of the SIRENE project is to identify immediate and longer term opportunities for commercialisation with high clinical and commercial feasibility. Therefore different business models will be studied in terms of market research, IP strategy and business development to eventually consolidate a commercial strategy and business case for presenting our business proposition to strategic partners or venture capitalists. Simultaneously, dose-range finding and efficacy studies will be conducted in rats, a clinically relevant and larger animal model of heart failure, for further preclinical development.

Mots-clés : mirna,antagomir,therapeutics,heart failure
Projet ERC : CSUMECH (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Aarhus University — Pays : Danemark — Rôle : PI
Acronyme de l'entité : AU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499848.0 €

Cardiovascular disease, diabetes and cancer have a dramatic impact on modern society, and in great part are related to uptake of cholesterol and sugar. We still know surprisingly little about the molecular details of the processes that goes on in this essential part of human basic metabolism. This application addresses cholesterol and sugar transport and aim to elucidate the molecular mechanism of cholesterol and sugar uptake in humans. It moves the frontiers of the field by shifting the focus to in vitro work allowing hitherto untried structural and biochemical experiments to be performed. Cholesterol uptake from the intestine is mediated by the membrane protein NPC1L1. Despite extensive research, the molecular mechanism of NPC1L1-dependent cholesterol uptake still remains largely unknown. Facilitated sugar transport in humans is made possible by sugar transporters called GLUTs and SWEETs, and every cell possesses these sugar transport systems. For all these uptake systems structural information is sorely lacking to address important mechanistic questions to help elucidate their molecular mechanism. I will address this using a complementary set of methods founded in macromolecular crystallography and electron microscopy to determine the 3-dimensional structures of key players in these uptake systems. My unpublished preliminary results have established the feasibility of this approach. This will be followed up by biochemical characterization of the molecular mechanism in vitro and in silico. This high risk/high reward membrane protein proposal could lead to a breakthrough in how we approach human biochemical pathways that are linked to trans-membrane transport. An improved understanding of cholesterol and sugar homeostasis has tremendous potential for improving general public health, and furthermore this proposal will help to uncover general principles of endocytotic uptake and facilitated diffusion systems at the molecular level.

Mots-clés : membrane protein structure,crystallography,single particle em,cholesterol uptake mechanism,sugar uptake mechanism
Projet ERC : RITA-MI (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Papworth Hospital NHS Foundation Trust — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 134136.0 €

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 : MorphoVES-PoC (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Johannes Gutenberg University Mainz — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149962.0 €

Cardiovascular diseases are the leading causes of mortality in Europe and worldwide. Currently, synthetic prostheses used in bypass vascular surgery are produced from polyethylene terephthalate [PET] and expanded polytetrafluoroethylene [ePTFE]. Those materials show less than optimal, insufficient biocompatibility and durability properties, especially if used for SMALL DIAMETER BLOOD VESSELS. Within the frame of ERC Advanced Grant “BIOSILICA” (From gene to biomineral: Biosynthesis and application of sponge biosilica; Grant No. 268476), we unexpectedly discovered that distinct natural, biodegradable and biofunctional polymers, including biosilica and inorganic polyphosphate (anionic), are not only bio-printable but also morphogenetically active. Likewise attractive is that those biopolymers can be functionally processed by non-toxic and charged (cationic) linkers with growth/differentiation potencies. Therefore, these formulations, backbone polymers and bioactive linkers, allowed the fabrication of unprecedented “Modular Small Diameter Vascular Grafts (MSDVGs)" which combine in an optimal way physical strength with physiological activity. Furthermore, the fabrication of the synthetic vessels is performed by a home-made, easy to handle, extruder device which has been developed by our group. Therefore, this new ERC-PoC project will provide small diameter (< 6 mm) blood vessel implants (incl. the fabrication device - the extruder) urgently required in clinics, with superior properties and at low-costs, at the end of the project. We are definitively convinced that, in view of their advantages, our vessels will be preferentially used for patients requiring bypass surgery. The experimental data gathered disclose that we have in hand a product with a clear biomedical application potential. Besides of their economical value, our new type of artificial blood vessel will certainly improve the quality of life and well-being of patients with cardiovascular disorders.

Mots-clés : cardiovascular diseases,atherosclerosis,prosthetic vascular grafts,biosilica,polyphosphate,small diameter blood vessels,extruder,morphogenetically active polymers
Projet ERC : X-Fold StereoGen (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Basel — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999266.0 €

Catalytic, stereoselective methodologies to study the control over the configuration of stereogenic elements with three- four-, five- and six-fold stereoisomerism are proposed. Previous catalyst-stereocontrolled methods allowed the differentiation of a twofold number of stereoisomers for any given stereogenic element. It is thus anticipated that expanding the stereogenicity in stereoselective catalysis represents a significant advance for the field. The reunification of conformational analysis and stereoisomerism in organic synthesis is expected to provide an improved conceptual framework. Traditionally, stereogenic elements are considered to generate a doubled number of possible stereoisomers, which are assigned with standard stereochemical descriptors such as R and S. The overall number of possible stereoisomers in a molecule with a set of stereogenic elements (n) is thus commonly predicted as 2^n. This binary stereochemical understanding of stereoisomerism represents a current basis for organic synthesis and a wide range of bioactive compounds critical for our health care are skillfully prepared by controlling the configuration of desired stereoisomers. Control over stereogenic elements that generate more than a twofold number of possible stereoisomers thus dramatically extents the scope of current stereoselective catalysis and organic synthesis. 1: The underpinnings of conformational analysis and the catalyst-stereocontrolled synthesis will be conceptually unequivocally reunited. 2: The uncharted setting of catalyst control over three-, four-, five- and six-fold stereogenicity will be established by the development of versatile synthetic methodologies. 3: Novel molecular architectures featuring unique chemical topologies will be assessible, representing unexplored chemical designs for a broad range of applications. 4: A divergent catalysis approach will be explored, utilizing common substrates for several stereoisomeric products with extended stereogenicity.

Mots-clés : stereoselective catalysis,stereochemistry,conformational analysis
Projet ERC : EarthMelt (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
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 : 3500000.0 €

Catastrophic planetary collisions during the Earth’s first 500 million years provided enough energy to melt its interior, creating planetary-scale volumes of melt, or magma oceans. Their cooling and crystallisation determined the chemistry of the Earth and its long-term habitability. However, we do not know where and how the Earth’s magma oceans crystallised, whether remnants of early magma ocean melts and crystals, or the iron-sulfide liquid that may have separated from them, are still preserved in the mantle today, or what their role is in storing the Earth’s volatiles and rare metals. We also do not know if this residual material remained inert or whether it interacted with mantle melting events during the course of Earth history, potentially transferring its precious cargo to the planet’s surface. The main barrier to studying magma oceans is that most of the evidence of them on Earth has been erased by the tectonic mixing processes that have operated over the past ~3 billion years. EarthMelt will address this issue by developing novel isotopic tools to study ancient magma ocean events. Iron and calcium stable isotopes show high-pressure phase-specific partitioning effects that can identify the molten and crystalline residues of magma oceans. Copper and platinum stable isotopes can be used to trace the separation of iron-sulfide melt from the silicate mantle and its incorporation in modern and ancient mantle melting regimes. EarthMelt will combine ultra-high precision measurements of these novel isotope systems with experiments simulating the conditions of magma ocean cooling and crystallisation and will apply these isotope tracers to rare samples of the Earth’s interior. EarthMelt will determine how the Earth’s magma ocean crystallised and how this influenced the physical structure and chemical composition of our planet, opening up a new approach to the study of magma oceans and their role in controlling terrestrial planet chemistry and habitability.

Mots-clés : stable isotopes,mass spectrometry,mantle melting,magma ocean
Projet ERC : SafeFate (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : German Cancer Research Center — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DKFZ
Type d'entité : Recherche
Financement ERC de l'entité : 1761489.0 €

Cell identity and function requires both induction of desired genes and repression of unwanted programs. While master regulators that activate gene networks during development are well characterized, the mechanisms that terminally repress alternative fates remain poorly understood. Within this project, I aim to demonstrate that active terminal repression is a universal mechanism required to prevent loss of cell identity and disease. We recently found that the neuron-specific transcription repressor Myt1l is essential to induce neuronal cell identity. Myt1l is expressed in virtually all neurons throughout life and its loss in mature neurons impairs neuronal gene expression and function, suggesting a role in maintaining cell fate. Unlike known repressors such as REST that specifically silences neuronal genes in non-neuronal cells, Myt1l represses many non-neuronal programs in neurons. I therefore propose that a new class of terminal repressor exists that continuously represses alternative lineages to confer and maintain cell identity. Since Myt1l mutations often occur in autism and schizophrenia I will investigate how loss of terminal repression can contribute to these poorly understood but common mental disorders. This will require molecular and behavioural studies in human and mouse models. We will also investigate how a sequence specific terminal repressor biochemically interacts with general epigenetic machinery to continuously silence unwanted programs during neuronal reprogramming. Finally, we will test candidate terminal repressors in other lineages by loss and gain of function approaches to analyse whether terminal repression is a universal principle of biology. Ultimately this will provide insight into fighting diseases associated with loss of cell identity and to efficiently generate cells for regenerative medicine using reprogramming.

Mots-clés : cell identity,cell fate reprogramming,transcriptional networks,neuroscience
Projet ERC : EvoCellMap (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
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 : 1498070.0 €

Cell types are the fundamental units of animal multicellularity. Distinct cell types are established and maintained by specific gene regulatory networks (GRNs), as well as epigenomic mechanisms that mediate the asymmetric access to genetic information within each cell. This cell regulation results in complex metazoan functions and structures. However, cell types and their regulation have only been characterized in a few species. Therefore, the origin and evolution of animal cell types remain largely unexplored, and so remains the evolution of the underlying GRNs and epigenomic mechanisms. In this project, we will develop a unified comparative framework to study cell type evolution and regulation from a multi-level and phylogenetic perspective. This project will focus on non-bilaterian metazoan lineages (Porifera, Ctenophora, Placozoa, and Cnidaria) as they are maximally informative towards reconstructing the evolutionary origins of metazoan genome regulation and of major cell types and their GRNs (e.g. neurons, secretory cells, stem cells, epithelial cells). To this end, we will integrate single-cell genomics and epigenomic profiling methods with advanced computational tools in order to: (1) investigate the origins of the animal regulatory genome; (2) characterize the diversity of cell type programs in non-bilaterian metazoans; and (3) model the structure and evolutionary dynamics of cell type-specific GRNs in these lineages. This evolutionary systems biology approach provides a complementary angle to both phylogenetically-restricted single-cell analyses and traditional cross-species studies based on targeted marker genes. Therefore, our results will fill a large gap of knowledge in our understanding of the origin and diversification of animal cell type programs and epigenomic mechanisms. In a broader context, this research program will provide unprecedented insights into the fundamental question of how cell types and their defining regulatory networks evolve.

Mots-clés : animal evolution,phylogenetic analysis,transcription factors,gene regulatory networks,single cell genomics,epigenomics