Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ProtMechanics-Live (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Ministry of Health — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Protein mechanics is a key contributor to the form and function of biological systems by mechanisms that are just starting to be unraveled. An ensuing hypothesis is that alteration of protein mechanics can trigger disease, particularly in mechanical conditions such as cardiomyopathies in which primordial underlying molecular mechanisms remain elusive. Although tempting, this possibility has not been tested due to the absence of methods that can modulate the mechanics of proteins in vivo. My proposal aims to overcome technical barriers to scientific progress by establishing manipulation of protein mechanics in living cells and animals as a new research field. In aim 1, we will address current technological limitations through the generation of genetic, protein-engineering-based mechanical loss- and gain-of-function models to interfere acutely and reversibly with protein mechanics in living systems (mLOF and mGOF, respectively). We will apply these first-of-their-kind tools to the giant protein titin, a major contributor to the force-generating and sensing properties of cardiomyocytes with strong links with heart disease, and a workhorse protein that has been instrumental in the past to understand the biophysics of polypeptides under force. In aim 2, we will exploit cellular mLOF and mGOF to define how perturbations of titin mechanics result in altered cardiomyocyte force generation, mechanosensing, mechanotransduction, differentiation and proliferation. Leveraging on our cell studies, in aim 3 we will use murine mLOF and mGOF to shed light into the contribution of titin mechanics to the onset and progression of genetic and acquired cardiomyopathy. ProtMechanics-Live builds on our unique expertise in protein mechanics and engineering, biophysics, biochemistry and cardiovascular biology to enable investigation of mechanical proteins in their functionally relevant, physiological context

Mots-clés : mechanobiology,sarcomere,cardiomyocyte,cardiomyopathy
Projet ERC : MisloQC (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Institute of Molecular Biology — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : IMB
Type d'entité : Recherche
Financement ERC de l'entité : 1497750.0 €

Protein quality control systems maintain a functional proteome through detection and removal of abnormal proteins. While typically only misfolded or damaged molecules are thought of as abnormal, recent work has revealed that also mislocalized proteins are subject to quality control. Mislocalized proteins are defined as proteins that fail to reach their native compartment or fail to assemble into their native complex, and thus cannot function normally. Protein mislocalization is a constitutive problem caused by inefficiencies of cellular processes and increases with aging. Proteins can also mislocalize due to mutations, as seen in various metabolic, cardiovascular and neurodegenerative diseases, and some types of cancer. Despite the ubiquity of protein mislocalization, the systems performing quality control of mislocalized proteins are unknown for most of the proteome because quality control substrates are usually rare, thus difficult to identify, and there is considerable redundancy built into quality control systems. Here, I propose to systematically dissect quality control mechanisms of mislocalized proteins through a combination of molecular biology, genetics, biochemistry and computational biology in yeast and human cells. We will establish a platform for conditional protein mislocalization and apply it (i) to identify quality control substrates proteome-wide, (ii) to dissect redundancies in quality control systems, (iii) to identify the machinery responsible for quality control of mislocalized proteins and (iv) to map the features involved in substrate recognition by the quality control machinery. Finally, we will exploit our findings to selectively target aneuploid cancer cells, which exhibit a high burden of mislocalized proteins. This work will provide a comprehensive picture of quality control systems for mislocalized proteins and shed light on their roles under both normal and perturbed conditions.

Mots-clés : protein quality control,proteome homeostasis,aneuploidy
Projet ERC : Orgasome (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Stockholm University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1331300.0 €

Protein synthesis in mitochondria is essential for the bioenergetics, whereas its counterpart in chloroplasts is responsible for the synthesis of the core proteins that ultimately converts sunlight into the chemical energy that produces oxygen and organic matter. Recent insights into the mito- and chlororibosomes have provided the first glimpses into the distinct and specialized machineries that involved in synthesizing almost exclusively hydrophobic membrane proteins. Our findings showed: 1) mitoribosomes have different exit tunnels, intrinsic GTPase in the head of the small subunit, tRNA-Val incorporated into the central protuberance; 2) chlororibosomes have divaricate tunnels; 3) ribosomes from both organelles exhibit parallel evolution. This allows contemplation of questions regarding the next level of complexity: How these ribosomes work and evolve? How the ribosomal components imported from cytosol are assembled with the organellar rRNA into a functional unit being maturated in different compartments in organelles? Which trans-factors are involved in this process? How the chlororibosomal activity is spatiotemporally coupled to the synthesis and incorporation of functionally essential pigments? What are the specific regulatory mechanisms? To address these questions, there is a need to first to characterize the process of translation in organelles on the structural level. To reveal molecular mechanisms of action, we will use antibiotics and mutants for pausing in different stages. To reconstitute the assembly, we will systematically pull-down pre-ribosomes and combine single particle with tomography to put the dynamic process in the context of the whole organelle. To understand co-translational operations, we will stall ribosomes and characterize their partner factors. To elucidate the evolution, we will analyze samples from different species. Taken together, this will provide fundamental insights into the structural and functional dynamics of organelles.
Projet ERC : MolDynForSyn (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University Hospital Bonn — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1207285.16 €

Proteins are the building blocks of life and neurons constantly need proteins to remain functional. This is a formidable challenge because neurons must regulate dendritic protein numbers across hundreds of micrometers, and need to redistribute proteins quickly in response to any synaptic changes. For example, long-term plasticity requires new proteins. Yet, it is still a puzzle how the available pool of proteins is redistributed via diffusion or active trafficking and how synaptic protein numbers are modified by increased translation of local mRNAs. Similarly, it is now an open question how the dysregulation of mRNA transport translates into plasticity impairments, how these modify circuit functions and ultimately lead to cognitive impairments. To answer these questions and connect the molecular dynamics to circuit function, we will develop a data-driven theory describing the dendritic mRNA and protein distributions in space and time and will use it to study the emergent synaptic plasticity dynamics in dendrites and its impact on memory storage. We will use data from leading experimental labs to identify how the unique combination of dendritic mRNAs, dendritic morphology, and synaptic activity gives rise to the synaptic protein dynamics that shapes circuit function. Our theory framework will generate and test hypotheses about how individual components such as mRNA motion, translation or degradation shape the protein exchange between synapses and clarify how they translate into multi-synapse synaptic plasticity rules that give rise to memory formation, memory generalization and separation. The unique combination of theory and experimental data will improve our understanding of long-term memory mechanisms and numerous neurological diseases that are associated with neuronal trafficking pathologies or protein synthesis dysfunction.

Mots-clés : neural circuits,protein dynamics,synaptic dynamics,neural network models,computational neuroscience
Projet ERC : TransTempoFold (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Proteins function only after folding into complex three-dimensional shapes. Loss of protein conformation is detrimental for cellular health, and a hallmark of aging and diverse human diseases. To ensure proteome integrity, cells rely on an intricate interplay between protein synthesis, folding, and quality control. Since proteins often begin to fold during mRNA translation, codon choice and tRNA supply can promote this process by modulating translation speed. How metazoans exploit this mechanism to ensure protein homeostasis over a wide range of cells and tissues, or why some cell types are more vulnerable to translation defects and proteome damage remains unknown. Here, I will define how tRNA pools and the regulatory networks for protein biogenesis and homeostasis are tailored to specialized proteomes in different cell types. I propose a multiscale systems approach centred around: i) stem cells and differentiated progeny lines as a powerful model system, and ii) a novel method to modulate cellular tRNA pools in vivo. Isogenic lines of a range of normal cellular states will be created through the differentiation of human pluripotent stem cells into neuronal and cardiac lineages. In these lineages, I will first quantitate tRNA expression and abundance, and dissect their impact on translation dynamics with ribosome profiling. Second, I will use systematic depletion of individual tRNAs to explore how different cell types respond to imbalanced tRNA pools, and define how mRNA sequence and protein structure patterns program protein folding. Third, I will use loss-of-function screens to uncover evolutionarily conserved regulators of proteome integrity as a function of cell identity. This project will define how diverse metazoan cell proteomes are established and maintained, and reveal why some cells tolerate misfolded proteins better than others.

Mots-clés : ribosome,trna,translation control,protein homeostasis
Projet ERC : StableCat (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Center odlicnosti nizkoogljicne tehnologije zavod — Pays : Slovénie — Rôle : Partner
Acronyme de l'entité : Co not
Type d'entité : Recherche
Financement ERC de l'entité : 5000.0 €

Proton exchange membrane fuel cells (PEMFC) are crucial in the race towards cutting the greenhouse gas emissions – covering 90.7% of total fuel cell market share already in 2018. PEMFCs as a zero-carbon technology converts hydrogen, as a fuel, and oxygen from the air into clean electricity, with water being the only by-product. In doing so, the catalyst material plays a crucial role. Currently, the most promising strategy is to use scarce and expensive platinum (Pt) in the form of carbon-supported nanoparticles (NPs) that are alloyed with a less expensive metal M (e.g. M = Ni, Co or Cu; Pt-M/C). However, current commercial catalyst solutions cannot yet combine the ‘three-pillars’ within the same material – (i) high electrochemically active surface area (ECSA), (ii) high catalytic activity and (iii) high stability. Thus, the StableCat project addresses the pressing need for the improvements of commercial catalysts by obtaining atomic-scale structural understanding. A unique methodological approach developed in project ERC StG 123STABLE resulted in a novel synthesis strategy that, for the first time, combines all three-pillars within the same catalyst material, and will pave the innovative way as an enabler for mass commercialisation of PEMFC technology. Our investigation revealed that 123STABLE catalysts exhibit up to 40% increase in ECSA, a 2-3 fold increase in catalytic activity, as well as an intermetallic crystal structure with increased stability towards corrosion. In addition, the new synthesis approach has also revealed significant potential at reducing the amount of Pt in PEMFCs (50% reduction possible already today). The goal of StableCat is to conduct technical and business activities necessary to enter the commercialisation phase, preferably in a form of a Spin-out company.

Mots-clés : proton exchange membrane fuel cells  pemfcs,platinum  pt,electrocatalysis,hydrogen,nanotechnology,value chain,intellectual property  ip,business development,commercialisation
Projet ERC : PuSH (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Newcastle University — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

PuSH – Pure, separated hydrogen from shift processes Here, I plan to exploit recent innovations made in my ERC Advanced Grant, SPeED, on the cyclic operation (or chemical looping) of chemical reactors to deliver transformational processes for chemical conversions relevant to the energy sector. We have recently shown (Nature Chemistry, 11, pages 638–643 (2019), video at http://nuvision.ncl.ac.uk/Play/18143) that a chemical looping reactor can produce pure, separated streams of carbon dioxide and hydrogen for a water-gas shift process (a key chemical process in hydrogen production) if and only if a non-stoichiometric oxide is used as the oxygen carrier material (OCM). Such new chemical looping processes have the potential to be a transformational development for the chemical industry and associated energy technologies because of the inherent carbon dioxide capture.

Mots-clés : hydrogen,carbon capture,process engineering,reaction engineering,chemical looping
Projet ERC : Niche Fibrosis (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 1499272.0 €

Pulmonary fibrosis is a multifaceted and fatal disease that includes damaged alveolar epithelial cells and disorganization of multiple stromal cells. Dysregulation of multicellular crosstalk between epithelial and stromal cells is likely to contribute to fibrosis. However, the precise way this tissue damage occurs is unknown. I hypothesize that impaired function of lung epithelial stem cell lead to alveolar epithelial damage in pulmonary fibrosis, and which may be caused by altered stromal/niche cells. Epithelial injury repair and regeneration in the adult lung is carried out by numerous epithelial stem/progenitor cells. Recently, I identified a crucial interaction between lung endothelial cells and lung stem cells during alveolar injury response, and demonstrated a new regulatory signalling pathway that operates in endothelial cells to support alveolar injury repair by driving alveolar lineage specification of stem cells. Importantly, introduction of endothelial-derived factors into the lung after fibrotic damage enhances alveolar regeneration and reduces pulmonary fibrosis. Given these results and unique my background knowledge, I will bring a new concept of stem cell-niche interactions in alveolar injury repair and pulmonary fibrosis. Using both in vivo murine and organoid culture, as well as human lung organoid culture systems, I will define 1) whether and how the fibrotic response affects lung stem cells and 2) how lung stem cells are regulated by endothelial cells that may comprise their respective niches during injury repair. 3) The mechanisms involved in the normal and pathological regulation of lung stem cells will be elucidated by determining secreted factors and regulatory signals endothelial cells confer through paracrine and direct physical interaction with stem cells. Insights gained from these studies will accelerate the development of novel and selective therapeutic approaches that directly target stem cells or their niches in pulmonary fibrosis.

Mots-clés : pulmonary fibrosis,vascular endothelial cells,lung stem cells,lineage differentiation,niche,oragnoid culture
Projet ERC : YoctoLHC (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Laboratory of Instrumentation and Experimental Particles Physics — Pays : Portugal — Rôle : Partner
Acronyme de l'entité : LIP
Type d'entité : Recherche
Financement ERC de l'entité : 399062.5 €

QCD is the only sector of the Standard Model where the exploration of the first levels of complexity, built from fundamental interactions at the quantum level, is experimentally feasible. An outstanding example is the thermalised state of QCD matter formed when heavy atomic nuclei are smashed in particle colliders. Systematic experimental studies, carried out in the last two decades, overwhelmingly support the picture of a deconfined state of matter, which behaves as a nearly perfect fluid, formed in a very short time, less than 5 yoctoseconds. The mechanism that so efficiently brings the initial out-of-equilibrium state into a thermalised system is, however, largely unknown. Most surprisingly, LHC experiments have found that collisions of small systems, i.e. proton-proton or proton-lead, seem to indicate the presence of a tiny drop of this fluid in events with a large number of produced particles. These systems have sizes of 1 fm or less, or time-scales of less than 3 ys. To add to the puzzle, jet quenching, the modifications of jet properties due to interactions with the medium, has not been observed in these small systems, while jet quenching and thermalisation are expected to be controlled by the same dynamics. Present experimental tools have limited sensitivity to the actual process of thermalisation. To solve these long-standing questions we propose, as a completely novel strategy, using jet observables to directly access the first yoctoseconds of the collision. This strategy needs developments well beyond the state-of-the-art in three subjects: i) novel theoretical descriptions of the initial stages of the collision — the first 5 ys; ii) jet quenching theory for yoctosecond precision, with new techniques to couple the jet to the surrounding matter and novel parton shower evolution; and iii) jet quenching tools for the 2020’s, where completely novel jet observables will be devised with a focus on determining the initial stages of the collision.

Mots-clés : large hadron collider,heavy ions
Projet ERC : QTONE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
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 : 2437500.0 €

QTONE aims at discovering new quantum phenomena involving THz vibrational modes, and at gaining control over them using novel concepts inspired from cavity quantum optomechanics and new techniques developed for nano-plasmonics and molecular break-junctions. The three main goals of the project are: (i) Perform optomechanical quantum information processing with THz phonons in low-dimensional systems, using a combination of ultrafast spectroscopy and time-correlated photon counting to measure quantum correlations mediated by non-classical vibrational states. (ii) Demonstrate the feasibility of dynamical backaction amplification of THz phonons by coupling molecules and nanomaterials to plasmonic cavities and by leveraging exciton-phonon coupling to realize exciton-assisted optomechanics. (iii) Interrogate and drive a single-molecule inside a plasmonic nanocavity using simultaneous inelastic electron tunneling and Raman spectroscopies in a molecular break-junction with engineered plasmonic resonance. I anticipate that this project will have widespread impacts on our understanding of quantum phenomena in molecular-scale oscillators, and will foster the excellence of Europe in fields ranging from fundamental science to quantum technologies and molecular electronics.
Projet ERC : QAffine (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Université Paris Cité — Pays : France — Rôle : Partner
Acronyme de l'entité : UP Cité
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 389250.0 €

Quantum affine algebras are important examples of Drinfeld-Jimbo quantum groups. They can be defined as quantizations of affine Kac-Moody algebras or as affinizations of finite type quantum groups (Drinfeld Theorem). The representation theory of quantum affine algebras is very rich. It has been studied intensively during the past twenty five years from different point of views, in particular in connections with various fields in mathematics and in physics, such as geometry (geometric representation theory, geometric Langlands program), topology (invariants in small dimension), combinatorics (crystals, positivity problems) and theoretical physics (Bethe Ansatz, integrable systems). In particular, the category C of finite-dimensional representations of a quantum affine algebra is one of the most studied object in quantum groups theory. However, many important and fundamental questions are still unsolved in this field. The aim of the research project is to make significant advances in the understanding of the category C as well as of its applications in the following five directions. They seem to us to be the most promising directions for this field in the next years : 1. Asymptotical representations and applications to quantum integrable systems, 2. G-bundles on elliptic curves and quantum groups at roots of 1, 3. Categorications (of cluster algebras and of quantum groups), 4. Langlands duality for quantum groups, 5. Proof of (geometric) character formulas and applications. The resources would be used for the following : (1) Hiring of 2 PhD students (in 2015 and 2017). (2) Hiring of 2 Postdocs (in 2015 and 2017). (3) Invitations and travel for ongoing and future scientific collaborations. (4) Organization of a summer school in Paris on quantum affine algebras.

Mots-clés : quantum groups,quantum integrable models,representations,infinite dimensional lie algebras,cluster algebras,categorification and geometry