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 Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1696074.54 €

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 : Newcastle University — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1433772.5 €

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 : NANOGEN (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
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 : 1635710.0 €

Energy harvesting (EH) from ambient vibrations originating from sources such as moving parts of machines, fluid flow and even body movement, has enormous potential for small-power applications such as wireless sensors, flexible, portable and wearable electronics, and bio-medical implants, to name a few. Nanoscale piezoelectric energy harvesters, also known as nanogenerators (NGs), can directly convert small scale ambient vibrations into electrical energy. Scavenging power from ubiquitous vibrations in this way offers an attractive route to supersede fixed power sources such as batteries that need replacing/recharging, and that do not scale with the diminishing size of modern electronics. This proposal aims to develop NGs for future self-powered smart devices. Ceramics such as lead zirconium titanate and semiconductors such as zinc oxide are the most widely used piezoelectric EH materials. This proposal however focuses on a different class of piezoelectric materials, namely ferroelectric polymers, such as polyvinlyidene fluoride (PVDF), its copolymers, and nylon. These are potentially superior EH materials as they are flexible, robust, lightweight, easy and cheap to fabricate, as well as being lead-free and bio-compatible. The key strategy of this proposal is in combining i) materials engineering to create novel piezoelectric polymer-ceramic nanocomposite materials with enhanced EH functionalities, ii) state-of-the art nanoscale characterization to explore and exploit these novel materials, and iii) fabrication of high performance NGs for implementation into commercial devices, using insight gained from modelling of materials and device parameters. The proposed research will culminate in a well-defined process for the large-scale production of highly efficient and low cost piezoelectric NGs with reliable EH performance to power the next generation of autonomous devices, thus steering the field into the renewable energy market as a clean and competitive technology.

Mots-clés : energy harvesting,nanogenerators,piezoelectric materials,ferroelectric polymers,sensors
Projet ERC : OMICON (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Graz University of Technology — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1494253.75 €

Energy storage is undeniably amongst the greatest societal challenges. Batteries will be key enablers but require major progress. Battery materials that promise a step-change in energy density compared with current Li-ion batteries rely on fundamentally different reactions to store charge, e.g. Si alloying or O2 reduction instead of intercalation. They have in common high volume changes on cycling and poor conductivity. For the active component of a battery electrode to function it must be simultaneously in contact with ionic and electronic pathways to electrolyte and current collector. State-of-the-art conducting additives and binders in the composite electrodes cannot ensure ideal contact for such materials and fail to exploit their full potential. In this project I directly target these fundamental challenges of high-energy batteries by replacing now used conducting additives and binders with flexible organic mixed ion and electron conductors that follow volume changes to ensure at any stage intimate contact with ions and electrons. This requires progress with the fundamental science of such conductors, for which to achieve we develop and combine synthetic, electroanalytic and spectroscopic methods, aided by theory. Mixed conducting polymer gels, designed for the particular storage material, shall be elaborated for two ultra-high capacity electrodes, the O2 cathode and the Si anode. The significant advantage, next to intimate contact, is that the packing density of active material can be maximized. This boosts energy stored by total electrode mass and volume by rigorously cutting the amount of non-active materials compared with current approaches. The expected overriding scientific impact includes improved understanding of mixed conductors concerning synthesis, structure, conductivity and their behaviour in the complex battery environment. This opens up new perspectives for the realm of high-capacity battery materials that demand such a breakthrough to succeed

Mots-clés : electron and ion transport in materials
Projet ERC : ECOWIZARD (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Engineered nanomaterials (ENMs) are widely used, and nanotechnological innovations grow with rapid pace. Studies on nanotoxicology have demonstrated that chemical toxicology as well as particle toxicology should be accounted for in predicting the safety of ENMs; and no simple correlation between toxic responses and mass, nanoparticle size or any other particle characteristic is found. Effects often occur only after long-term exposure, whereas evidence of acute toxicity induced by ENMs is limited. Hence, current hazard assessment lacks accurate approaches to assess the safety of ENMs at species level nor does it accounted knowledge for knowledge on how ENMs affect species relationships. To overcome these problems, I address within my proposal 2 key gaps: 1) The current lack of understanding of the chronic effects of ENMs at environmentally relevant conditions at the individual species level as well as at higher ecological levels including considerations of species interactions. 2) The current lack of transferability of dose and response knowledge allowing to extrapolation towards untested (advanced) ENMs and untested species. The EcoWizard project aims to acquire fundamental and generalizable insights into the chronic effects on species and species interactions induced by long-term exposure to (advanced) ENMs at environmentally relevant conditions. My ambitious aim is to combine lab-based experiments and field-realistic mesocosm experiments in tandem with ecophysiological modelling and ecological modelling. Results obtained during this project will ultimately break new grounds by providing the first fundamental insights into the chronic impacts of ENMs on organisms and species interactions, explicitly accounting for the ‘ecology’ in ecotoxicology. The project results will generate the backbone of new ecological-based models that allow to quantify the environmental impact of newly developed ENMs and that are broadly applicable to other ecosystems.

Mots-clés : environmental toxicology,ecotoxicology,fate of chemicals and nanomaterials,species relationships,bioavailability,dose response,predictive safety modelling
Projet ERC : justITSELF (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999075.0 €

Engineers and computer scientists are currently developing autonomous systems whose entire set of behaviors in future, untested situations is unknown: How can a designer foresee all situations that an autonomous road vehicle, a robot in a human environment, an agricultural robot, or an unmanned aerial vehicle will face? Keeping in mind that all these examples are safety-critical, it is irresponsible to deploy such systems without testing all possible situations---this, however, seems impossible since even the most important possible situations are unmanageably many. I propose a paradigm shift that will make it possible to guarantee safety in unforeseeable situations: Instead of verifying the correctness of a system before deployment, I propose just-in-time verification, a new, to-be-developed verification paradigm where a system continuously checks the correctness of its next action by itself in its current environment (and only in it) in a just-in-time manner. Since future autonomous systems will have a tight interconnection of discrete computing and continuous physical elements, also known as cyber-physical systems, I will develop just-in-time verification for this system class. In order to prove correct behavior of cyber-physical systems, I will develop new formal verification techniques that efficiently compute possible future behaviors---subject to uncertain initial states, inputs, and parameters---within a small time horizon. Just-in-time verification will substantially cut development costs, increase the autonomy of systems (e.g., the range of deployment of automated driving systems), and reduce or even eliminate certain liability claims. The results will be implemented in an open-source software framework and will be primarily demonstrated for automated driving. Successful development of just-in-time verification techniques is yet more challenging than offline verification of autonomous systems, but expected to bring even greater rewards.

Mots-clés : reachability analysis,formal verification,autonomous systems,hybrid systems,conformance checking
Projet ERC : COMANFLO (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
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 : 1959323.0 €

Entropy (admissible) weak solutions are widely considered to be the standard solution framework for hyperbolic systems of conservation laws and incompressible Euler equations. However, the lack of global existence results in several space dimensions, the recent demonstration of non-uniqueness of these solutions and computations showing the lack of convergence of state of the art numerical methods to them, have reinforced the need to seek alternative solution paradigms. Although one can show that numerical approximations of these nonlinear PDEs converge to measure-valued solutions i.e Young measures, these solutions are not unique and we need to constrain them further. Statistical solutions i.e, time-parametrized probability measures on spaces of integrable functions, are a promising framework in this regard as they can be characterized as a measure-valued solution that also contains information about all possible multi-point spatial correlations. So far, well-posedness of statistical solutions has been shown only in the case of scalar conservation laws. The main aim of the proposed project is to analyze statistical solutions of systems of conservation laws and incompressible Euler equations and to design efficient numerical approximations for them. We aim to prove global existence of statistical solutions in several space dimensions, by showing convergence of these numerical approximations, and to identify suitable additional admissibility criteria for statistical solutions that can ensure uniqueness. We will use these numerical methods to compute statistical quantities of interest and relate them to existing theories (and observations) for unstable and turbulent fluid flows. Successful completion of this project aims to establish statistical solutions as the appropriate solution paradigm for inviscid fluid flows, even for deterministic initial data, and will pave the way for applications to astrophysics, climate science and uncertainty quantification.

Mots-clés : uncertainty quantification,turbulence modeling,monte carlo algorithms,measure valued solutions
Projet ERC : QUADAG (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : University of Duisburg-Essen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2124663.0 €

Enumerative geometry, the mathematics of counting numbers of solutions to geometric problems, and its modern descendents, Gromov-Witten theory, Donaldson-Thomas theory, quantum cohomology and many other related fields, analyze geometric problems by computing numerical invariants, such as intersection numbers or degrees of characteristic classes. This essentially algebraic approach has been successful mainly in the study of problems over the complex numbers and other algebraically closed fields. There has been progress in attacking enumerative problems over the real numbers; the methods are mainly non-algebraic. Arithmetic content underlying the numerical invariants is hidden when analyzed by these non-algebraic methods. Recent work by the PI and others has opened the door to a new, purely algebraic approach to enumerative geometry that recovers results in both the complex and real cases in one package and reveals this arithmetic content over arbitrary fields. Building on these new developments, the goals of this proposal are, firstly, to use motivic homotopy theory, algebraic geometry and symplectic geometry to develop new purely algebraic methods for handling enumerative problems over an arbitrary field, secondly, to apply these methods to central enumerative problems, recovering and unifying known results over both C and R and thirdly, to use this new approach to reveal the hidden arithmetic nature of enumerative problems. In 2009 R. Pandharipande and I applied algebraic cobordism to prove the degree zero MNOP conjecture in Donaldson-Thomas theory. More recently, I have developed several aspects of the theory of quadratic invariants using motivic homotopy theory.

Mots-clés : enumerative geometry,quadratic forms,motivic homotopy theory,gromov witten theory,hermitian k theory,chow witt groups
Projet ERC : RNArepair (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1808200.0 €

Enzymatically active RNA-guided proteins, like the RNA-induced silencing complex (RISC), are particularly versatile tools for the rationally programmed manipulation of genetic information. After successful re-addressing of various natural RNA-guided machineries it is now time to tackle the engineering of novel, user-defined tools. With this respect we have recently achieved the engineering of an RNA-guided adenosine-to-inosine RNA editing machinery. Since inosine is biochemically read as guanosine, A-to-I editing alters genomic information on the RNA-level and may potentially allow for the manipulation of RNA processing or protein function. We have already achieved to apply our RNA editing approach for the repair of several missense and nonsense point mutations on reporter and disease-related genes in vitro and demonstrated its applicability in mammalian cell culture. Now, we want to push the method further towards application. To enable editing in oocytes, primary cells and neurons, we will establish to deliver the editing tool by lentiviral vectors and stabilized mRNAs. We further aim to create cell lines expressing the artificial editing machinery under conditional control. We will repair reporter genes in developing worm oocytes, and we want to reconstitute mutations that cause neuro-diseases. We also wish to establish new features including photocontrol and the application of editing to steer protein localization. If successful, site-directed RNA editing will enable us to manipulate RNA and protein function in a yet unprecedented way. The ready introduction of point mutations into mRNAs without the need for genomic engineering may dramatically facilitate the study of protein function, disease mechanism and may even allow for the treatment of diseases based on personalized genetic information.

Mots-clés : photochemistry
Projet ERC : BioNet (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
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 : 968817.5 €

Enzymes created by Nature are still more selective and can be orders of magnitude more efficient than man-made catalysts, in spite of recent advances in the design of de novo catalysts and in enzyme redesign. The optimal engineering of either small molecular or of complex biological catalysts requires both (i) accurate quantitative computational methods capable of a priori assessing catalytic efficiency, and (ii) molecular design principles and corresponding algorithms to achieve, understand and control biomolecular catalytic function and mechanisms. Presently, the computational design of biocatalysts is challenging due to the need for accurate yet computationally-intensive quantum mechanical calculations of bond formation and cleavage, as well as to the requirement for proper statistical sampling over very many degrees of freedom. Pioneering enhanced sampling and analysis methods have been developed to address crucial challenges bridging the gap between the available simulation length and the biologically relevant timescales. However, biased simulations do not generally permit the direct calculation of kinetic information. Recently, I and others pioneered simulation tools that can enable not only accurate calculations of free energies, but also of the intrinsic molecular kinetics and the underlying reaction mechanisms as well. I propose to develop more robust, automatic, and system-tailored sampling algorithms that are optimal in each case. I will use our kinetics-based methods to develop a novel theoretical framework to address catalytic efficiency and to establish molecular design principles to key design problems for new bio-inspired nanocatalysts, and to identify and characterize small molecule modulators of enzyme activity. This is a highly interdisciplinary project that will enable fundamental advances in molecular simulations and will unveil the physical principles that will lead to design and control of catalysis with Nature-like efficiency.

Mots-clés : enhanced sampling alogrithms,free energy calculations,phosphate catalysis