Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ANGI (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
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 : 1999970.0 €

Our ability to predict adaptation and the response of populations to selection is limited. Solving this issue is a fundamental challenge of evolutionary ecology with implications for applied sciences such as conservation, and agronomy. Non genetic inheritance (NGI; e.g., ecological niche transmission) is suspected to play a foremost role in adaptive evolution but such hypothesis remains untested. Using quantitative genetics in wild plant populations, experimental evolution, and epigenetics, we will assess the role of NGI in the adaptive response to selection of plant populations. The ANGI project will follow the subsequent research program: (1) Using long-term survey data, we will measure natural selection in wild populations of Antirrhinum majus within its heterogeneous array of micro-habitats. We will calculate the fitness gain provided by multiple traits and stem elongation to plants growing in bushes where they compete for light. Stem elongation is known to depend on epigenetic variation. (2) Using a statistical approach that we developed, we will estimate the quantitative genetic and non genetic heritability of traits. (3) We will identify phenotypic changes caused by fitness that are based on genetic variation and NGI and assess their respective roles in adaptive evolution. (4) In controlled conditions, we will artificially select for increased stem elongation in clonal lineages, thereby excluding DNA variation. We will quantify the non genetic response to selection and test for a quantitative epigenetic signature of selection. (5) We will build on our results to generate an inclusive theory of genetic and non genetic natural selection. ANGI builds on a confirmed expertise in selection experiments, quantitative genetics and NGI. In addition, the availability of survey data provides a solid foundation for the achievement of this project. Our ambition is to shed light on original mechanisms underlying adaptation that are an alternative to genetic selection.

Mots-clés : non genetic inheritance,heritability,response to selection,adaptive potential
Projet ERC : SPIN (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1893553.0 €

Our ability to remember past events and experiences lies at the core of cognition and behaviour. But how do fleeting moments get converted into durable memory traces? Recent work has highlighted the pivotal role of post-learning sleep for successful memory consolidation, the process of stabilising new memories over time. However, little is known about the neurophysiological mechanisms through which the sleeping brain consolidates new memories. Not only has this left a gap in our understanding of memory formation as a whole, but also the means to modulate memories during sleep have remained underexplored. SPIN will test the exciting hypothesis that particular electrophysiological signatures of sleep, namely sleep spindles, are the mechanistic vehicle driving memory consolidation. Specifically, I hypothesise that in coordination with hippocampal reactivation events, sleep spindles are deployed to cortical learning sites where they induce lasting structural changes. Using intracranial recordings from the human hippocampus (measuring single neuron firing and associated ‘ripple’ oscillations) and from an array of cortical areas, we will first establish whether spindles are temporally aligned with hippocampal reactivation events. Next, we will use high-density scalp EEG and functional as well as structural MRI in healthy participants to test whether spindle deployment to cortical learning sites predicts structural changes in these regions. To assert causality, we will examine the effects of invasive spindle perturbation in patients on memory consolidation. Finally, we will experimentally enhance local spindles to harness their potential as a tool for boosting human memory. In sum, SPIN will use an unprecedented array of human brain recording and stimulation techniques to provide a mechanistic link between learning, sleep and structural brain changes, culminating in novel tools to enhance human learning and memory.

Mots-clés : memory,sleep,consolidation,brain imaging,brain stimulation
Projet ERC : FunctionalProteomics (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Hungarian Academy of Sciences — Pays : Hongrie — Rôle : PI
Acronyme de l'entité : MTA
Type d'entité : Recherche
Financement ERC de l'entité : 2498750.0 €

Our astonishing cognitive abilities are the consequence of complex connectivity within our neuronal networks and the large functional diversity of excitable nerve cells and their synapses. Investigations over the past half a century revealed dramatic diversity in shape, size and functional properties among synapses established by distinct cell types in different brain regions and demonstrated that the functional differences are partly due to different molecular mechanisms. However, synaptic diversity is also observed among synapses established by molecularly and morphologically uniform presynaptic cells on molecularly and morphologically uniform postsynaptic cells. Our hypothesis is that quantitative molecular differences underlie the functional diversity of such synapses. We will focus on hippocampal CA1 pyramidal cell (PC) to mGluR1α+ O-LM cell synapses, which show remarkable functional and molecular heterogeneity. In vitro multiple cell patch-clamp recordings followed by quantal analysis will be performed to quantify well-defined biophysical properties of these synapses. The molecular composition of the functionally characterized single synapses will be determined following the development of a novel postembedding immunolocalization method. Correlations between the molecular content and functional properties will be established and genetic up- and downregulation of individual synaptic proteins will be conducted to reveal causal relationships. Finally, correlations of the activity history and the functional properties of the synapses will be established by performing in vivo two-photon Ca2+ imaging in head-fixed behaving animals followed by in vitro functional characterization of their synapses. Our results will reveal quantitative molecular fingerprints of functional properties, allowing us to render dynamic behaviour to billions of synapses when the connectome of the hippocampal circuit is created using array tomography.

Mots-clés : synaptic neurotransmission,hippocampus,immunohistochemistry,patch clamp,electrophysiology,two photon imaging
Projet ERC : NEWSFLOWS (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1496671.0 €

Our beliefs about society are largely based on information that we encounter through media. This happens more and more in an "unbundled” form: Single news items are distributed through sharing on social media, sorted by algorithms, and encountered on platforms on which they were not originally published. Many argue that this leads to so-called “echo chambers” and “filter bubbles”, communities of people that are only exposed to information they agree with. This is thought to lead to increasing polarization of society, and to a lack of diversity in people’s (virtual) communities. But a growing body of evidence suggests that these metaphors are misleading. In fact, as recent discussions on so-called “fake news” illustrate, biased and/or extreme information is not locked up in filter bubbles or echo chambers, but spreads from niche communities into mainstream media and politics. NEWSFLOWS develops an alternative model of how information spreads in today’s media ecosystem – a model based on so-called feedback loops, which are essential for the modern complex system of information flows. To give an example of a feedback loop: If a news item receives many shares on social media, this may let a recommendation algorithm show it to even more users (and journalists and politicans), making it more likely that they will act on it, again increasing the number of shares, etc. Crucially, neither the algorithm, nor the users, nor the writers alone determine the eventual spread, but a combination of their influences and feedback loops. Theoretical models and empirical methods to study such feedback loops in the social sciences and humanities are scarce. NEWSFLOWS extends innovative methods as online field experiments, data donations, and automated content analysis to conduct such studies. This will greatly enhance the theoretical understanding of news flows, but also enable media organizations to develop products conforming to calls for "responsible AI".

Mots-clés : news use,news dissimination,selective exposure,echo chamber,filter bubble
Projet ERC : CosmicWeb (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of Milano-Bicocca — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIMIB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Our cosmological model predicts that most of the matter in the universe is distributed in a network of filaments - the Cosmic Web - in which galaxies form and evolve. Because most of this material is too diffuse to form stars, its direct imaging has remained elusive for several decades leaving fundamental questions still open, including: what are the morphological and kinematical properties of the Cosmic Web on both small (kpc) and large (Mpc) scales? How do galaxies get their gas from the Cosmic Web? In this programme, I will tackle these questions with an innovative method and technology that allows us to directly detect in emission the gaseous Cosmic Web before the peak of galaxy formation, when the universe is less than 3 billion years old: using bright quasars and galaxies as “cosmic flashlights” to make the gas “fluorescently” glow. Although challenging, detecting such emission is possible: I have recently demonstrated that some parts of the Cosmic Web illuminated by bright quasars can be detected in both hydrogen Lyman-alpha and H-alpha emission. These pilot studies and new instruments such as VLT/MUSE and the James Webb Space Telescope (JWST; available from 2021) are the ideal stepping stones for a revolution in the field, the main goals of this programme: 1) direct imaging of the average Cosmic Web extending on cosmological scales (tens of Mpc) in the young universe, away from quasars; 2) revealing the small-scale distribution (below one kpc) of gas within Cosmic Web filaments. For this aim, I will use the deepest available observations to date, including a 160-hours deep integration that is being obtained through our MUSE Guaranteed Time of Observations, and future ground-based Adaptive-Optics and JWST infrared H-alpha observations. These datasets will be combined with new data analysis methods and numerical models that will be specifically developed in this programme opening up a completely new window to study cosmic structure and galaxy formation.

Mots-clés : intergalactic medium,lyman alpha emission,observations and theory,integral field spectroscopy,three dimensional data analysis,radiative transfer,hydrodynamical simulations
Projet ERC : DNA2REPAIR (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2203153.0 €

Our genetic material is continually subjected to damage, either from endogenous sources such as reactive oxygen species, produced as by-products of oxidative metabolism, from the breakdown of replication forks during cell growth, or by agents in the environment such as ionising radiation or carcinogenic chemicals. To cope with DNA damage, cells employ elaborate and effective repair processes that specifically recognise a wide variety of lesions in DNA. These repair systems are essential for the maintenance of genome integrity. Unfortunately, some individuals are genetically predisposed to crippling diseases or cancers that are the direct result of mutations in genes involved in the DNA damage response. For several years our work has been at the forefront of basic biological research in the area of DNA repair, and in particular we have made significant contributions to the understanding of inheritable diseases such as breast cancer, Fanconi anemia, and the neurodegenerative disorder Ataxia with Oculomotor Apraxia (AOA). The focus of this ERC proposal is: (i) to determine the mechanism of action and high-resolution structure of the BRCA2 tumour suppressor, and to provide a detailed picture of the interplay between BRCA2, PALB2, RAD51AP1 and the RAD51 paralogs, in terms of RAD51 filament assembly, using biochemical, electron microscopic and cell biological approaches, (ii) to determine the biological role of a unique structure-selective tri-nuclease complex (SLX1-SLX4-MUS81-EME1-XPF-ERCC1), with particular emphasis on its roles in DNA crosslink repair and Fanconi anemia, and (iii) to understand the actions of Senataxin, which is defective in AOA2, in protecting against genome instability in neuronal cells. These three distinct and yet inter-related areas of the research programme will provide an improved understanding of basic mechanisms of DNA repair and thereby underpin future therapeutic developments that will help individuals afflicted with these diseases.

Mots-clés : tumourigenesis,neurodegenerative disorders,dna damage response,recombination,repair,transcription
Projet ERC : DNA ORIGAMI MOTORS (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
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 : 2000000.0 €

Our goal is to advance the field of DNA nanotechnology by achieving directed transport on the nanoscale using robustly functioning synthetic motor units. To do so, we propose to construct spatially periodic, diffusive mechanisms that have broken inversion symmetry and to subject these mechanisms to conditions away from thermal equilibrium. We will build on recent progress in creating complex DNA-based structures and construct various nanoscale rotary and translational Brownian ratchet mechanisms that have well- defined degrees of freedom for motion within periodic and asymmetric energy landscapes. The mechanisms will be self-assembled from DNA origami components. We will use cryo-Transmission Electron Microscopy (TEM) to evaluate and iteratively refine our structures. Conventional video-rate fluorescence microscopy, in addition to super-resolution microscopy, will be employed to study in solution and in real time the diffusive motion of the mechanisms on the single particle level. We will introduce various deterministic or stochastic thermal, mechanical, or chemical perturbations to drive the systems away from thermal equilibrium. We will use laser heating and cooling to experimentally test thermal and flashing ratcheting mechanisms; we will employ dissipative asymmetric fluxes arising in active matter as realized in high-density ATP-hydrolysing motility assays; and we will couple out-of-equilibrium chemical reactions to the motion of our mechanisms. The ultimate goal of our work is to take insights from these experiments and create robustly functioning nanoscale motor units that can drive directed motion against external load and perform at levels comparable to those of natural macromolecular motor proteins. Achieving this goal will create unprecedented technological opportunities, for example, to drive chemical synthesis, actively propel nanoscale drug- delivery vehicles, pump and separate molecules across barriers or package molecules into cargo components.

Mots-clés : self assembly,dna nanotechnology
Projet ERC : GAP60PTP (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Isea sweden kommanditbolag — Pays : Suède — Rôle : Partner
Acronyme de l'entité : Isea
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 106268.75 €

Our idea is to enable the next generation of mobile network infrastructure for high speed data communication through the use of a new technology platform called gap waveguides. The demand for mobile data is growing rapidly and operators see their costs for mobile infrastructure rising. To meet the demand, and at the same time manage costs, the industry is looking at an increased adoption of smaller, more cost-efficient mobile base stations (small cells) closer to the end-user. These are expected to be connected wirelessly through high bandwidth point-to-point (PTP) solutions operating at 60 GHz and above. To be used at scale, these PTP solutions must fit into the city landscape, be cost-efficient, and easy to install. However, current radio frequency (RF) technology at 60 GHz leads to bulky and expensive products with poor performance as losses increase dramatically with frequency. Gap waveguides is a newly invented technology platform for constructing microwave circuits, which has been shown to have inherently low losses. Our concept is to apply the gap waveguide technology to RF front-ends in PTP solutions. The objective with the proof-of-concept study is to understand the market need for an integrated 60 GHz RF front-end in more detail, and evaluate potential mass production methods to verify the concept’s commercial viability. The study will be performed in four phases: (1) A pre-study capturing the current research status and detailing the project plan; (2) A market verification including market, customer competitive analyses; (3) A mass production method evaluation to identify and evaluate potential methods for machining and assembly of gap waveguide based components; and (4) A definition of the way forward summarizing key findings, conclusions, drafting of plans for market entry and production development. A team consisting of the Principle investigator, a project manager, a business analyst and an external technology expert will perform the study.

Mots-clés : telecommunication,wireless technology,60 ghz,point to point,small cells,technology platform,rf front end,microwave electronics
Projet ERC : PHAGOSCOPY (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Delft University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU Delft
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1438510.0 €

Our immune system provides a formidable barrier to the many microbial pathogens that we encounter every day. Yet, many pathogens have the ability to avert this barrier by invading the host cell and seeking shelter inside a phagosome whose membrane physically prevents the pathogen from being recognized and eliminated. Cell-autonomous immunity is a part of the innate immune system that fights off such pathogens. Among the antimicrobial effectors mobilized by this immune response are the Guanylate-Binding Proteins (GBPs). GBPs form dynamic supramolecular assemblies that promote lysis of phagosomes and, thus, killing of pathogens. Despite their central importance, we know very little about the molecular mechanisms of GBPs. Two fundamental questions are: (1) What is the structure and composition of GBP assemblies on membranes?, and (2) Once assembled, how do the GBPs structurally rearrange to reshape and rupture the phagosome's membrane? These questions remain unanswered because structural biology has been lacking methods for determining dynamically changing structures of proteins that are assembled in complex environments such as phagosomes. Here, I propose to take a two-pronged approach to address these questions: first, I will use cryo-EM and (single-molecule) fluorescence microscopy to elucidate the interactions and conformational changes involved in GBP oligomerization on model membranes. Second, I will visualize this pathway on native phagosomes using a recently developed ex vivo reconstitution system unique to my laboratory. By determining how GBP assemblies form on phagosome membranes, how they reshape the membrane so that it ruptures, and how these processes can be regulated and inhibited, I will derive a mechanistic model of a key effector function that cells employ to combat disease-causing pathogens. More broadly, my study will establish a novel approach for integrative imaging that will be applicable to a wide range of dynamic molecular assemblies in cells.

Mots-clés : cryo em,cryo tomography,structural biology,macromolecular assemblies,sample preparation,nanotechnology