Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MUM-GROW (Horizon 2020, appel 2020, Consolidator 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 : 1999910.0 €

Life on Earth is sustained by plants. Growth and development in the plant kingdom is mediated by the controlled distribution of sugars and the hormone auxin, but we still know surprisingly little about the molecular details of this essential part of fundamental plant metabolism. MUM-GROW will elucidate the molecular mechanism of sugar and auxin transmembrane transport in plants. It moves the frontiers of the field by shifting the focus to molecular studies in vitro allowing structural and biochemical experiments to be performed. Correct plant growth and development is completely dependent on sugar uptake in growth zones (the meristem), and made possible in all plants by sugar transporters called SUCs and STPs. Growth polarity is created by an asymmetrical gradient of auxin mediated by auxin transporters called PINs. Despite extensive research, the molecular mechanisms of SUC, STP and PIN transport remains unknown. If we knew the molecular determinants of their function, it would allow us to predict, augment and possibly modify plant responses to a changing environment. I will address this using a complementary set of methods founded in structural biology to determine the 3-dimensional structures of key players in these transmembrane transport systems. This will be combined with biochemical characterization to address important mechanistic questions and elucidate their molecular mechanism. Understanding the mechanisms that govern plasticity in growth is essential for determining resilience of whole ecosystems. This proposal will lead to a breakthrough in our understanding of sugar and auxin homeostasis, a fundamental part of basic plant metabolism. It has tremendous potential for the societal challenge to secure sufficient food for our global population in a sustainable balance between environmental impact and resource exploitation. Furthermore, this proposal will uncover general molecular principles of transmembrane uptake and export pertaining to all organisms.

Mots-clés : membrane proteins,crystallography,cryo em,sugar transport,hormone transport,plant growth,plant development
Projet ERC : DDX TRANSIT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Basel — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499845.0 €

Life ultimately depends on the tight control of gene expression, which requires an ordered and efficient processing of various RNA molecules. Messenger RNAs (mRNAs) – bound by a constantly changing coat of passenger proteins - transit from transcription in the nucleus to translation and ultimately decay in the cytoplasm. Similarly, ribosomal rRNAs migrate through the nucleolus where they gradually en-counter ribosomal proteins to assemble functional ribosomes. Still, we know very little about the pro-cesses that orchestrate this flux of RNA in a temporal and spatial manner. Intriguingly, many RNA processing steps occur in membraneless organelles formed by liquid-liquid phase separation, e.g. nuclear speckles or the nucleolus, but the function of condensate formation in RNA processing is not known. I have discovered that the family of DEAD-box ATPases (DDXs) are master regulators of RNA-containing membraneless organelles, from bacteria to man. DDXs use their low-complexity domains and ATPase activity to regulate condensate dynamics and RNA flux through these compartments. I propose that cells use DDX-controlled condensate ‘stations’ to establish an RNA ‘transit map’ to reg-ulate the cellular flux of mRNA and rRNA molecules and to spatially and temporally control RNA pro-cessing. In three work packages, I will (1) characterize central DDXs that control mRNA flux and use DDX mutants as unique tools to map passenger protein changes along the life of an mRNA; (2) charac-terize how DDXs regulate the formation of the phase-separated nucleolar environment and facilitate the flux of rRNA during ribosome assembly; (3) dissect how DDX condensates function as biomolecular filters to selectively enrich or exclude proteins, and how selectivity contributes to the remodeling of the RNA protein coat and directional RNA flux. Our research will provide key novel insight into our understanding of RNA processing and uncover novel layers of gene expression regulation.

Mots-clés : dead box atpases,liquid liquid phase separation,membraneless organelles,mrna,rrna,rna protein complexes,rna flux
Projet ERC : BIOSPACE (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Twente — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2252676.25 €

Life, with all its diversity, is in crisis. As humans increasingly encroach on biologically complex semi- natural landscapes, no organism, place or ecological function remains unaffected. While all 196 parties (195 countries plus the European Union) to the UN Convention on Biodiversity (CBD) have agreed to monitor the state of biodiversity, the currently available methods to do so leave much to be desired. Traditional monitoring involves the field observation of species by trained specialists, aided by skilled volunteers, whose expertise is restricted to specific biotic groupings. In a process that is both time consuming and inconsistent across time and space, botanists identify and record the presence of plant species and ornithologists the bird biota, resulting in 'unpopular' biotic groups such as fungi, bacteria and insects being under-observed or escaping identification altogether. In this project, a fundamentally different approach to terrestrial biodiversity monitoring couples next generation satellite remote sensing with environmental DNA (eDNA) profiling, complemented where available by legacy human-observed datasets. Satellite remote sensing is able to survey the environment as a single, continuous, fine-resolution map, while eDNA profiling can rapidly quantify much greater taxonomical and functional breadth and depth than human field observation. This project combines, for the first time, these two powerful, cutting-edge techniques for monitoring biodiversity at the global level in a consistent manner. Following from this, another key innovation will be the deepening of our scientific understanding of how biodiversity is impacted by anthropogenic pressure as well as by natural environmental gradients. In concert, these scientific developments will enable the accurate and fine grain monitoring of biodiversity from space – a ground-breaking contribution to the quest to meet the UN Sustainable Development Goals and CBD Aichi targets.
Projet ERC : EXPLORATOME (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Life-threatening cues such as the scent of smoke or the taste of rotten food cause avoidance behavior in animals. In such situations, instantaneous integration of relevant sensory inputs by motor centers that guide navigation can be a matter of life and death. How is this sensorimotor integration achieved? In vertebrates, it is known that motor command centers in the brainstem receive direct inputs from higher brain areas and cutaneous sensory pathways and in turn control the spinal circuits that drive locomotion. It is less well understood whether these brainstem command neurons are simple integrators relaying information, or whether they add a layer of integration to select locomotor action sequences. Because brainstem neurons are difficult to visualize and access in mammals, it has been challenging to measure their activity in moving animals as they respond to sensory cues. In contrast, larval zebrafish is a simpler vertebrate model in which optical technologies can be leveraged to visualise, record, and manipulate any and/or all brainstem neurons during locomotion. This project will decode the neuronal computations of descending command neurons that integrate sensory inputs and elicit locomotor actions in freely-moving zebrafish larvae. To this end, my group has designed an unbiased method for segmenting locomotor action sequences from noisy behavioral data. Applied to robust assays where larvae navigate in chemical gradients, we are now in a unique position to link locomotor action sequences to the sensory landscape fish perceive. This original approach, together with innovative technologies pioneered in my lab, will reveal brainstem neuronal connectivity and roles in the selection of locomotor sequences. The EXPLORATOME project will lead to models of circuit computations in the brainstem, a brain region historically-overlooked and with high potential for targeted electrical stimulations in patients with motor disorders.

Mots-clés : brainstem,reticulospinal neurons,locomotor action sequences,exteroception,proprioception,navigation,zebrafish
Projet ERC : SINCHAIS (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2481437.0 €

Ligand-gated and voltage-gated channels are key molecules in transforming chemical signals into electrical ones and electrical signals into chemical ones, respectively. At excitatory synaptic connections in the brain, activation of AMPA- and NMDA-type glutamate receptors elicits inward currents at the postsynaptic sites, and activation of voltage-gated calcium channels triggers vesicle release of glutamate in the presynaptic sites. Plastic changes in their number, location and property can lead to potentiation or depression of synaptic efficacy, alteration in time course, and coupling to effectors at both postsynaptic and presynaptic sites. These channels are all composed of distinct subunits and their compositions affect channel properties, trafficking to the synaptic sites, and interaction with associated molecules, creating a large diversity of synaptic functions. Although channels with different subunit compositions have been investigated using biochemical and electrophysiological detection methods, very little is known about single channel subunit composition in situ because of the lack of high resolution methods for analysis of protein complex in intact tissues. In this project, I will develop novel technologies to visualize subunit composition at the single channel level in individual synapses by electron microscopy, combining new EM tags, freeze-fracture replica labelling, and electron tomography. Synaptic plasticity will be induced by optogenetic stimulation of identified neurons or behavioural paradigms to examine the dynamic changes of subunit composition. Finally, physiological implications of such regulation of subunit composition will be investigated by genetic manipulation of mice combined with electrophysiological and behavioural analyses. This work will demonstrate unprecedented views of the subunit composition in situ and provide new insights into how regulation of subunit composition contributes to synaptic plasticity and animal behaviour.

Mots-clés : glutamate receptors,ca channels,subunit composition,synaptic plasticity,electron microscopy
Projet ERC : PHAROS (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Regensburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2458200.0 €

Light is a fascinating reagent for chemistry as it provides energy to drive reactions, but leaves no trace. In visible light photoredox catalysis the initial electron transfer from the excited dye to a substrate yields radical anion or radical intermediates, which dominate the subsequent chemistry. Carbanions, which are the most important nucleophiles in organic chemistry, are typically not available from photocatalysis. The project PHAROS aims to overcome the current limitation of visible light photocatalysis to radical chemistry and extend its use to carbon nucleophiles. To obtain carbanions for organic synthesis using visible light, we propose three specific project tasks: 1) We develop the next generation of visible light photocatalysts extending the current energetic limit of bond activation required for carbanion generation. This task is based on our recently developed consecutive photoinduced electron transfer (conPET) strategy accumulating the energy of more than one photon for synthesis. Now, the reduction power is further increased reaching potentials of alkali metals and allowing sequential two-electron transfers as needed for preparing carbanions. 2) This technology is then used to generate carbanions from neutral starting materials by visible light photoinduced one- or two-electron transfer. The concept allows a light-driven synthetic carbanion chemistry without the stoichiometric use of reducing reagents, such as magnesium, zinc or lithium. 3) Faster and cleaner reactions, longer catalyst lifetimes and selective photocatalytic sequences are achieved by sensitized photocatalysts and pulsed light excitation. This will enhance the overall energy efficiency of photoredox catalysis facilitating practical applications. The energy of visible light provides the redox energy to generate carbanions for organic synthesis and thereby broadens the synthetic use of the most abundant and sustainable energy source on earth, visible light.

Mots-clés : carbanion,electron transfer,photoredox catalysis,visible light
Projet ERC : RNActivate (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Münster — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : WWU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1990225.0 €

Light is an excellent external regulatory element that can be applied to cells and organisms with high spatio-temporal precision and without interfering with cellular processes. Optochemical biology exploits small photo-responsive chemical groups to cage and activate or to switch biomolecular functions in response to light of a defined wavelength. Caged antisense agents have enabled down-regulation of gene expression with spatio-temporal control at the messenger-RNA (mRNA) level in vivo, however approaches for triggering translation of exogenous mRNA lack efficient turn-on effects. To explore the effects of conditional and transient ectopic gene expression in a developing organism it is vital to fully abrogate and restore translational efficiency. The goal of this project is to bring eukaryotic mRNA under the control of light to trigger efficient ectopic translation with spatio-temporal resolution in cells and in vivo. To achieve this, eukaryotic mRNA will be photo-caged at its 5′ cap using a highly promiscuous methyltransferase capable of transferring very bulky moieties from synthetic analogs of the cosubstrate S-adenosylmethionine (AdoMet). A single 5′ cap modification will block translation of the respective mRNA. Its light-triggered removal will release unmodified capped RNA, which in cells will be efficiently remethylated to form the canonical 5′ cap resulting in uncompromised translation. In addition to labeling and tracking subpopulations of cells, we will use our technology to control and to manipulate cell fate by locally producing proteins responsible for cell death, genome engineering, and cell migration. We will use cultured cells and one-cell stage zebrafish embryos that can be easily injected with mRNA to study the function of ectopic gene expression in early development. Our approach will overcome current limitations of photo-inducible mRNA translation and enable us to manipulate a developing organism at the molecular level.
Projet ERC : ThermoTON (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1993265.0 €

Limiting the number of people affected by significant aircraft noise is one of the most important tasks of modern civil aviation. Among different contributors, tonal noise is the most important due to regulatory definitions and its attenuation characteristics, with the largest contributor being the fan aero-acoustics. Current passive noise reduction methods alone are insufficient to conform with the increasingly stringent noise emission regulations. This motivates our research in active noise cancellation, based on creation of equal amplitude and frequency pressure waves, in opposite phase to the disturbance. Having identified that the actuator technology is the main hindrance against hardware implementation in flying platforms, we have been investigating a revolutionary technology based on a truly static and surface-deposited sound emitter (thermophone), which creates pressure fields by thermo-acoustic effects rather than the vibro-acoustics utilized by common speakers. Comprising of a periodically Joule heated electrically conductive thin layer, a highly efficient thermophone requires modeling of non-Fourier heat conduction in deposits. The project is divided into 4 multi-disciplinary objectives: 1. Derivation of accurate macro-scale heat conduction model, including non-Fourier effects 2. Developing thermophone performance model by analyzing thermo-acoustic effect 3. Optimization of performance by material and geometric selection, and by manufacturing processes 4. Demonstrating aero-acoustic fan noise cancelation via the thermo-acoustic effect created by static heat flux transducer In addition to the significance that this project will have to the field of aviation, I strongly believe that successful completion of each work package will provide dramatic improvements over the state of the arts in conduction heat transfer modelling, consumer electronics such as speakers, manufacturing methods for thermo-acoustic devices, and active aero-acoustic noise cancellation.

Mots-clés : non fourier heat transfer modelling,electro thermo acoustic conversion,thermophone optimization,advanced manufacturing techniques,speaker technologies,active noise cancellation,aviation noise
Projet ERC : MultiMotif (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 504218.69 €

Linear motifs are short sequence stretches that occur in intrinsically disordered protein regions (IDRs) lacking stable secondary and tertiary structure, and mediate vital interactions within various biological systems. An exemplary system for the presence of IDRs and a high concentration of linear motifs is the clathrin mediated endocytosis machinery of the eukaryotic cell, where a complex interaction network of IDR-rich adaptor proteins enables both protein and lipid interactions. The molecular mechanism of such interactions, especially when multiple motifs act in concert, is however only poorly understood particularly since the dynamic and flexible nature of IDRs makes them a very difficult object to study. I aim to develop an integrative approach based on single molecule fluorescence and NMR spectroscopies to characterize the molecular principles of IDRs in clathrin mediated endocytosis. A systematic analysis of IDRs with different types of motifs and various interaction partners will not only shed light on the molecular functions of linear motifs within endocytosis, but also on how multiplicities of linear motifs may work in various biological processes in general. In vitro structural studies will be connected with single molecule imaging to relate molecular conformation with function within the cell.

Mots-clés : intrinsically disordered proteins
Projet ERC : PURA (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Ca' Foscari University of Venice — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1303437.0 €

Linguistic purism, the attempt to protect language against the ‘threat’ of multilingualism, change and outside contact, finds an antecedent in Greek Antiquity that remains mostly unknown outside Classics and has never been studied in a multidisciplinary perspective. PURA aims to overturn this state of affairs by producing the first global study of Greek purism, the texts which upheld it, and their legacy in later ages. The focus of this analysis are Atticist lexica: collections of features to be cultivated or avoided in correct Greek. These texts were compiled by scholars who lived in the multilingual Roman Empire and wished to counter the natural evolution of Greek by freezing it at an ideal stage of purity, identified with the extinct dialect of 5th-century Athens. PURA is characterized by a multidisciplinary methodology combining Classics, linguistics, textual philology, codicology and historical lexicography which will tackle both the immaterial heritage of Atticist theories and their material history as books. Its objectives are: 1) to provide a global mapping of the purist theories expressed in the lexica and make them both accessible outside the traditional format of critical editions and approachable for non-experts in the form of a unique web-based searchable corpus; 2) to endow the corpus with an in-depth linguistic analysis that extends from Ancient to Modern Greek; 3) to bring textual transmission and book circulation into the picture by charting all the manuscripts and first printed editions of the lexica; 4) to produce the definitive study of Atticism and its legacy from a modern linguistic and philological perspective. PURA will go beyond the traditional standards of Classical studies by creating a model of textual, linguistic and philological analysis for the investigation of Ancient Greek lexicography that can be extended to the study of purism in other languages and cultures.

Mots-clés : ancient greek,medieval greek,modern greek,greek linguistics,lexicography,codicology