Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : EPIMODKIT (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Tamaserv ug — Pays : Allemagne — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 50000.0 €

Epitranscriptomic modifications constitute specific marks in mRNA that regulate gene expression. Identification of epitranscriptomic modifications requires next generation sequencing analyses and specific validation, processes that are cumbersome and time consuming. Furthermore, while some modifications are straightforward to identify, as they cause specific base changes (like RNA editing), most are only detectable either through chemical means (requiring large quantities of material) or by immunoprecipitation followed by sequencing. Of these techniques, immunoprecipitation requires far less material and can be used in any molecular biology laboratory, but depends exquisitely on the quality of the monoclonal antibodies that recognize the modification - their specificity, selectivity and sensitivity. Most anti-modification antibodies are generated using traditional methods for the production of monoclonals to small molecule haptens (e.g. conjugation to a large protein carrier and injection into animals together with an adjuvant). While these methods can generate anti-hapten responses with some specificity they are generally not very selective. We have developed a novel immunization platform that exquisitely focuses the antibody response to a hapten to generate high affinity monoclonals with a high degree of specificity. We propose to employ this approach to generate anti-inosine antibodies (for the detection of editing in disease contexts); anti-m6A antibodies (which would be benchmarked against the ones currently in use, validating our approach); and antipseudo-uridine antibodies (a tool that is lacking in the field and for which traditional approaches have completely failed). The generation of specific and selective antibodies to these three modifications, will open the way toward a better understanding of their intricate molecular roles in biological proceGenerating monoclonal antibodies that selectively and specifically recognize epitranscriptomic modifications.

Mots-clés : rna editing,rna modification,epitranscriptomic modifications,anti modification antibodies
Projet ERC : IlluMitoDNA (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1851834.0 €

Essential subunits of the mitochondrial respiratory chain, which generates the majority of energy in eukaryotic cells, are encoded in the mitochondrial genome (mtDNA) that is present in hundreds of copies in every cell. Mutations within mtDNA have been identified as the cause for a multitude of human diseases and have been tightly linked to the ageing process and altered stem cell homeostasis. Accordingly, to ensure organismal health, good copies of mtDNA have to be faithfully inherited during cell division, their integrity needs to be maintained over generations and they need to be distributed throughout the mitochondrial network to provide all mitochondrial segments with mtDNA encoded proteins. Astonishingly, it remains poorly understood how cells accomplish these fundamental tasks. Through the development of a novel system that for the first time allowed minimally invasive tracking of mtDNA in living cells, we have gained unique insights into the cellular principles that govern distribution and inheritance of mtDNA and the maintenance of its integrity. This work paved the way to understand the molecular mechanisms that underlie these processes and provides the tools required to elucidate them. We will build on this work and combine cutting-edge microscopy and next generation sequencing with biochemical and genetic approaches to identify and characterize the machineries responsible for (1) mtDNA inheritance and distribution and (2) mtDNA quality control. While these first two aims will exploit the unique experimental advantages of S. cerevisiae, our ultimate goal is (3) to transfer our findings to higher eukaryotes through the development of a mammalian mtDNA imaging system. This powerful multipronged approach will mechanistically unravel mtDNA dynamics and quality control and will thus provide the necessary basis to understand diseases where these processes are dysregulated.

Mots-clés : mitochondria,mitochondrial dna  mtdna,yeast,s  cerevisiae
Projet ERC : CRYTOCOP (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 1275036.44 €

Eukaryotic cells are organised in membrane-bound compartments, which have defined chemical identities and carry out specific essential functions. Exchange of material between these compartments is necessary to maintain cell functionality, and is achieved in a highly specific and regulated manner by vesicular transport. To mediate protein trafficking, coat complexes assemble on membranes and couple bilayer deformation with cargo capture into transport carriers. How coat assembly can deliver the flexibility necessary to accommodate a wide variety of cargo proteins, and how the process can be regulated, are outstanding questions in the field. This is exemplified by the COPII coat, which mediates export from the ER of about a third of newly synthesized proteins. COPII assembles into two concentric layers and can form transport carriers of a variety of shapes and sizes, including tubules and spherical vesicles. This is important for export of large cargoes and is a process targeted by cargo-specific regulatory factors. The aim of this project proposal is to shed light on the molecular interactions between coat components, and understand their role in determination of coat architecture and membrane shape. We will use a combination of structural and functional approaches to characterise COPII coat assembly, and its relationship with membranes in systems of increasing complexity, ranging from in vitro reconstitutions to cells. In particular, we will use cryo-electron tomography and subtomogram averaging to understand the architecture of the coat layers in these systems. These are fast-developing techniques that uniquely target complex structures while achieving high resolutions. With my lab at the forefront of current advances, we are perfectly placed to obtain a complete view of the COPII coat assembled on membranes. Our research will answer outstanding questions in the membrane trafficking field and open new perspectives to tackle ill-characterised regulation systems.

Mots-clés : cryo electron tomography,membrane trafficking,coat protein complex ii
Projet ERC : CRYTOCOP (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 224138.56 €

Eukaryotic cells are organised in membrane-bound compartments, which have defined chemical identities and carry out specific essential functions. Exchange of material between these compartments is necessary to maintain cell functionality, and is achieved in a highly specific and regulated manner by vesicular transport. To mediate protein trafficking, coat complexes assemble on membranes and couple bilayer deformation with cargo capture into transport carriers. How coat assembly can deliver the flexibility necessary to accommodate a wide variety of cargo proteins, and how the process can be regulated, are outstanding questions in the field. This is exemplified by the COPII coat, which mediates export from the ER of about a third of newly synthesized proteins. COPII assembles into two concentric layers and can form transport carriers of a variety of shapes and sizes, including tubules and spherical vesicles. This is important for export of large cargoes and is a process targeted by cargo-specific regulatory factors. The aim of this project proposal is to shed light on the molecular interactions between coat components, and understand their role in determination of coat architecture and membrane shape. We will use a combination of structural and functional approaches to characterise COPII coat assembly, and its relationship with membranes in systems of increasing complexity, ranging from in vitro reconstitutions to cells. In particular, we will use cryo-electron tomography and subtomogram averaging to understand the architecture of the coat layers in these systems. These are fast-developing techniques that uniquely target complex structures while achieving high resolutions. With my lab at the forefront of current advances, we are perfectly placed to obtain a complete view of the COPII coat assembled on membranes. Our research will answer outstanding questions in the membrane trafficking field and open new perspectives to tackle ill-characterised regulation systems.

Mots-clés : cryo electron tomography,membrane trafficking,coat protein complex ii
Projet ERC : BUNDLEFORCE (Horizon 2020, appel 2015, 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 : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1499190.0 €

Eukaryotic cells constantly convert signals between biochemical energy and mechanical work to timely accomplish many key functions such as migration, division or development. Filopodia are essential finger-like structures that emerge at the cell front to orient the cell in response to its chemical and mechanical environment. Yet, the molecular interactions that make the filopodia mechanosensitive are not known. To tackle this challenge we propose unique biophysical in vitro and in vivo experiments of increasing complexity. Here we will focus on how the underlying actin filament bundle regulates filopodium growth and retraction cycles at the micrometer and seconds scales. These parallel actin filaments are mainly elongated at their barbed-end by formins and cross-linked by bundling proteins such as fascins. We aim to: 1) Elucidate how formin and fascin functions are regulated by mechanics at the single filament level. We will investigate how formin partners and competitors present in filopodia affect formin processivity; how fascin affinity for the side of filaments is modified by filament tension and formin presence at the barbed-end. 2) Reconstitute filopodium-like actin bundles in vitro to understand how actin bundle size and fate are regulated down to the molecular scale. Using a unique experimental setup that combines microfluidics and optical tweezers, we will uncover for the first time actin bundles mechanosensitive capabilities, both in tension and compression. 3) Decipher in vivo the mechanics of actin bundles in filopodia, using fascins and formins with integrated fluorescent tension sensors. This framework spanning from in vitro single filament to in vivo meso-scale actin networks will bring unprecedented insights into the role of actin bundles in filopodia mechanosensitivity.

Mots-clés : mechanotransduction,actin cytoskeleton,filopodia,actin bundle,formin,fascin,microfluidics
Projet ERC : RESOLUTION (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 0.0 €

Europe was the continent where Neanderthal and Anatomically Modern Human (AMH) interacted in a supposed time window of up to five millennia around 40,000 years ago (40 ka BP). The fate of our species versus the demise of Neanderthals, the geospatial timing of this process, the behavioural implications of their interaction, are hotly debated topics in archaeology. In this context, chronology plays a pivotal role, with radiocarbon (14C) dating representing the backbone back to 50 ka BP. However, due to varying atmospheric 14C concentrations in the past, the method requires calibration to an independently dated archive. So far, only the past 14 ka BP can profit from the most direct natural archive of 14C activity, which are annually resolved tree-ring chronologies. Before this time, temporal resolution is remarkably lower and different calibration records disagree, leading to discrepancies in the calibration of up to 2000 years. This project aims to achieve for the first time an accurate and highly resolved chronology back to 50 ka BP, to establish the timing of when AMHs arrived in Europe, their interaction with Neanderthals and the final cause of Neanderthal extinction. The project involves fieldwork in Mediterranean and southeast Europe to find more glacial trees, the study of the existing collection of glacial conifers, exceptional 14C precision for 14C dates in the Glacial, and the cutting-edge methodology in linking floating tree-ring chronologies to 10Be on the ice core scale. The results of this work will be crucial in solving some of the most interesting puzzles in European prehistory. With tree-rings, the resolution will be an order of magnitude higher, and using the most recent advances in the AMS technique, we will obtain confidence intervals of only a few centuries in glacial times. This project will be of pivotal importance for key periods in human evolution.

Mots-clés : human evolution,radiocarbon dating,dendrochronology,cosmogenic isotope,neanderthal,anatomically modern human
Projet ERC : ArtEmpire (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Pavia — Pays : Italie — Rôle : Partner
Acronyme de l'entité : UNIPV
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 140750.0 €

European incursions onto the narrow isthmian pass that divided and connected the Atlantic and Pacific oceans made it a strategic node of the Spanish Empire and a crucial site for early modern globalization. On the front lines of the convergence of four continents, Old Panama offers an unusual opportunity for examining the diverse, often asymmetrical impacts of cultural and commercial contacts. The role of Italian, Portuguese, British, Dutch, and French interests in the area, as well as an influx of African slaves and Asian merchandise, have left a unique material legacy that requires an integrated, interdisciplinary approach to its varied sources. Bones, teeth and artifacts on this artery of Empire offer the possibility of new insights into the cultural and biological impact of early globalization. They also invite an interdisciplinary approach to different groups’ tactics for survival, including possible dietary changes, and the pursuit of profit. Such strategies may have led the diverse peoples inhabiting this junction, from indigenous allies to African and Asian bandits to European corsairs, to develop and to favor local production and Pacific trade networks at the expense of commerce with the metropolis. This project applies historical, archaeological and archaeometric methodologies to evidence of encounters between peoples and goods from Europe, America, Africa and Asia that took place on the Isthmus of Panama during the sixteenth and seventeenth centuries. Forging an interdisciplinary approach to early globalization, it challenges both Euro-centric and Hispano-phobic interpretations of the impact of the conquest of America, traditionally seen as a demographic catastrophe that reached its nadir in the so-called seventeenth-century crisis. Rather than applying quantitative methods to incomplete source material, researchers will adopt a contextualized, inter-disciplinary, qualitative approach to diverse agents involved in cultural and commercial exchange.

Mots-clés : conquest,commerce,cultural exchange,global history,globalization
Projet ERC : EXPLO (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Aristotle University of Thessaloniki — Pays : Grèce — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1069743.0 €

European societies today face unprecedented environmental change. Understanding how human societies responded to past challenges of environmental change relates to the interface between culture and environment. The EXPLO project proposes a novel interdisciplinary approach to investigate key questions regarding the interaction between past human ways of life, land use and the wider environment through a unique combination of archaeological, biological and dynamic mathematical modelling approaches. Archaeological prehistoric sites in lakes of northern Greece and the southern Balkans provide an excellent opportunity to investigate rich archives of societal and environmental change in the cradle of European farming. Natural lake sediments and submerged prehistoric settlements offer exceptional preservation conditions and uniquely holistic insights into past anthroposphere, biosphere and geosphere dynamics. More than 8,000 years ago, technological and social breakthroughs allowed the introduction of farming from western Asia to Greece and thus for the first time to Europe; however, so far there is no high-resolution picture of how this revolutionary innovation interacted with the environment, including its long-term consequences. New underwater archaeological research will allow the construction of highly precise settlement chronologies on the basis of dendrochronology, radiocarbon dating and Bayesian modelling. On-site information from excavations will be combined with off-site palaeoenvironmental data from the same lakes to investigate past adaptation strategies to the environment as well as the effects of past societies on their environments. Dynamic models integrating archaeological contexts and palaeoenvironmental data will open up the opportunity to investigate vulnerability, resilience, tipping points and thresholds of ancient agrarian economies, with implications for future food systems under a rapidly changing climate.

Mots-clés : neolithic,bronze age,paleoecology,bioarchaeology,balkans,northern greece,wetlands,underwater archaeology,early agropastoral societies,lande use,anthropogenic land cover land use change
Projet ERC : MATTER (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Duisburg-Essen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1180398.56 €

Ever since the discovery of topological surface states in three-dimensional (3D) topological insulators (TI), this fascinating physics has thrilled scientists. While arguable the transport properties of 3D TIs are of utmost importance for potential applications, they are extremely difficult to characterize, yet utilize for devices. The reason is that transport in those materials is always dominated by bulk carriers. Within this proposed research project, I will overcome the problem of bulk carrier domination conceptually by a nanoparticle-based materials’ design of interrupted early stage sintering. By this interrupted early stage sintering approach, I compact 3D TI nanoparticles at mild temperature and low pressure. The obtained highly porous macroscopic sample features a carrier density of the surface states in the order of 1018 cm-3, hence in a comparable order of magnitude as the bulk carrier density. Further, the interruptedly sintered nanoparticles impose energetic barriers for the transport of bulk carriers (hopping transport), while the connected surfaces of the nanoparticles provide a 3D percolation path for surface carriers. Within the preliminary work, my group tuned interruptedly sintered nanoparticles into a transport regime completely dominated by the surface states. Within this project, nanoparticle-based macroscopic 3D TI materials will be developed towards test structures for devices. Their properties will be tailored by the nanoparticle synthesis (Objective 1) and the materials processing of interrupted early stage sintering (Objective 2). This is complemented by an in-depth characterization of the transport as well as spectroscopic properties and data modelling (Objective 3). My group will use this know-how for the fabrication of test devices (Objective 4). This combination will provide the first macroscopic quantum transport devices that utilize the unique electronic properties of surface states, overcoming the problem of bulk carrier domination

Mots-clés : nanoparticle processing,topological insulator,transport properties,sintering
Projet ERC : LOCOLEARN (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Champalimaud Foundation — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1999375.0 €

Every movement we make requires us to coordinate our actions precisely in space and time. This proposal aims to understand how that remarkable coordination is achieved by neural circuits controlling movement. The cerebellum plays a critical role in keeping movements calibrated and coordinated, and it is thought to do this in part through a motor learning process in which predictable perturbations of movement are gradually compensated. Cerebellum-dependent forms of motor learning have been identified for a variety of behaviors, including locomotion, and locomotor learning is used as a rehabilitative therapy in human patients. We recently established locomotor learning in mice, using a custom-built, transparent split-belt treadmill that controls the speeds of the two sides of the body independently and allows for high-resolution behavioral readouts. Here, we will combine quantitative analysis of locomotor behavior with genetic circuit dissection to answer two fundamental questions: How are cerebellar outputs read out by downstream circuits, to calibrate spatial and temporal components of movement? and How are instructive signals for spatial and temporal learning encoded by cerebellar inputs? Specifically, we will: 1) Use circuit tracing combined with manipulation of specific cerebellar outputs to identify downstream pathways for spatial and temporal locomotor learning, 2) Investigate the role of error signals for cerebellar learning via optogenetic perturbation of climbing fiber inputs to the cerebellum, and 3) Image complex spike activity from populations of Purkinje cells during locomotion and learning, to ask how spatial and temporal error signals are encoded within the cerebellum. These studies will allow us to bridge levels of analysis to understand how cerebellar learning mechanisms convert behaviorally-relevant sensorimotor error signals into calibration signals that ensure accurate and coordinated movements in space and time for a wide range of behaviors.

Mots-clés : cerebellum,motor learning,neural circuits,locomotion,mouse