Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CN Identity (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Erasmus MC — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1400000.0 €

How does the brain integrate diverse sensory inputs and generate appropriate motor commands? Our cerebellum is a key region for such a sensorimotor processing, empowered by its sophisticated neural computation and constant communication with other brain regions. The well-timed cerebellar information is integrated and funneled to other brain regions through the cerebellar nuclei (CN). Yet, how CN circuitry contributes to the cerebellar control of sensorimotor processing is unclear. My recent work indicates that the CN activity serves various functions ranging from the online motor control, the amplitude amplification of cerebellar outputs to the control of motor planning. Given these advances, I am now in a unique position to decipher the properties of CN neurons and identify their specific roles in different forms of sensorimotor processing. It is my central hypothesis that depending on the specific demands of the task, CN neurons can either facilitate or suppress the activity of downstream regions with millisecond precision; and the anatomical, genetic and functional properties of CN neurons are tailored to the particular task involved. To test this hypothesis, I will 1) identify the activity patterns of different CN modules during the acquisition and execution of two sensorimotor tasks and characterize the relevant extra-cerebellar inputs to these modules; 2) identify the connectivity-transcription logic of different CN modules and link them to their task-specific outputs; and 3) examine the impacts of manipulating anatomically and/or genetically defined CN neurons on the downstream regions during different sensorimotor tasks. I will accomplish these key objectives by developing various novel electrophysiological, optogenetic, molecular and imaging techniques. My research is likely to break new ground, demonstrating that the identity of CN neurons is determined by their differential temporal demands of sensorimotor tasks controlled by different brain structures.

Mots-clés : cerebellar nuclei,sensorimotor processing,cortico cerebellar loop
Projet ERC : CLAUSTRUM (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

How does the brain integrate inputs from the environment to generate perception and drive decisions? An enigmatic brain region called the claustrum has been suggested to play a role by integrating inputs from multiple brain regions. There is strong interconnectivity between claustrum and nearly every neocortical brain region, indicating that it exerts widespread influence on brain function. However, approaches to specifically record from or manipulate activity in the claustrum have been hindered by the inability to target it selectively. This has been difficult due to the anatomy of the claustrum: it is a long, thin bilateral nucleus buried between the neocortex and the striatum. This proposal aims to understand the role of the claustrum in multisensory integration and behaviour by developing new approaches for monitoring and manipulating the activity of the claustrum. We will harness recent advances in electrophysiological, genetic, optical, and behavioural tools to probe its connectivity, activity, and function in a precise manner. Understanding the role of the claustrum in brain function will provide fundamental insight into information processing in the neocortex, which is a major goal in neuroscience. The claustrum is unique because of its dense reciprocal connectivity with neocortex but nearly complete lack of direct subcortical sensory input. This particular anatomical structure indicates the possibility of a unique function, but none has been observed yet. This proposal will rectify the paucity of data on this distinctive structure by applying a battery of modern tools to address the function of the claustrum. Experiments will address the following key questions: 1. How are claustrocortical inputs integrated and what is the effect of corticoclaustral feedback? 2. What is the activity of claustral neurons during sensory stimulation and motor output? 3. What are the causal relationships between claustrum activity and animal behaviour?

Mots-clés : claustrum,mouse,behaviour,optogenetics,calcium imaging,two photon
Projet ERC : DYNAMIC_ENGRAM (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

How does the brain store and retrieve information over time? The accepted notion that these processes rely on the neuronal ensembles that were active during learning is now challenged by findings by our lab and others that reveal that different neurons and networks than those that were active during learning support persistent memory. Most notably, we found that the long-term persistence of spatial memory is correlated with the degree to which neuronal activity is spatially informative, but not with the stability of the coding carried by individual neurons. These discoveries—obtained via novel imaging technologies that enable, for the first time, to track large populations of the same neurons over weeks—expose a fundamental gap in our understanding and highlight the need to reveal how neural codes across brain circuits, including the hippocampus, entorhinal cortex, and prefrontal cortex, change over the lifetime of a memory. Here we propose to investigate the mechanisms that govern the reorganization of memory using innovative methods we recently developed for optical imaging, large-scale data analysis, and circuit manipulation. Key among them is our ability to simultaneously and longitudinally image in two related brain areas the activity of large neuronal populations in freely behaving mice. Using these new tools, we will elucidate the factors governing the circuit dynamics of memory representations (Aim 1); how such dynamics relate to the behavioral manifestation of memory (Aim 2); how hippocampal-cortical and cortical-cortical interactions change over weeks to support remote memory (Aim 3); and what mechanisms could underlie the transfer of learned information between neurons in a network (Aim 4). Our approach will allow us to resolve how systems-level consolidation is realized at the neural code level, both within and across brain areas, and how a stable memory is maintained over the long term despite an ever-changing neuronal representation.

Mots-clés : long term memory,hippocampus,entorhinal cortex,prefrontal cortex,calcium imaging,place cells,grid cells,memory consolidation,engram
Projet ERC : LoopingDNA (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
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 : 2500000.0 €

How is DNA spatially organized in our cells? What are the mechanisms that shape chromosomes and how does their 3D architecture direct their function? Recent years have shown that the spatial structure of the genome is of pivotal importance for its biological function. Yet, the basic physics of the formation and regulation of its 3D structure has remained unclear. This proposal aims to understand the fundamental structure of chromosomes using a bottom up biophysics approach, from looping at the single-molecule level to higher levels of complexity. We focus on so-called SMC protein complexes (SMC = Structural Maintenance of Chromosomes). These ring-shaped proteins are a unique new type of molecular motors that can extrude large loops of DNA that are thought to be the basis of chromosome structure. Our group’s recent breakthrough discovery of the looping motor function of condensin SMC paved the way to now answer major open questions, such as the motor mechanism of SMCs; how SMCs handle realistic chromosomal fibers loaded with DNA-binding proteins; how looping relates to gene expression; and whether it is evolutionary conserved from bacteria to man. By answering these questions using single-molecule assays, we will resolve the basic mechanics of the SMC-induced looping of DNA. We will extend this to even build a chromosome from the bottom up, in a ‘genome-in-a-box’ approach where we will take genome-length bare DNA and add SMC protein complexes and other DNA-processing proteins. Such a well-controlled bottom-up approach – which to our knowledge is unique – can be expected to generate a radically new understanding of the physical forces and protein systems that shape chromosomes. We are confident that our powerful single-molecule biophysics tools, in collaboration with working with the world’s best biochemists, will enable to disentangle the fundamental looping architecture of chromosomes that is so essential to all of life.

Mots-clés : smc protein complexes,single molecule techniques,biophysics,dna loop extrusion,biomolecular motors,dna protein interactions,dna polymer physics,chromosome structure,bottom up approach
Projet ERC : MacroStability (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

How neuronal circuits maintain the balance between stability and plasticity in a constantly changing environment remains one of the most fundamental questions in neuroscience. Empirical and theoretical studies suggest that homeostatic negative feedback mechanisms operate to stabilize the function of a system at a set point level of activity. While extensive research uncovered diverse homeostatic mechanisms that maintain activity of neural circuits at extended timescales, several key questions remain open. First, what are the basic principles and the molecular machinery underlying invariant population dynamics of neural circuits, composed from intrinsically unstable activity patterns of individual neurons? Second, is homeostatic regulation compromised in Alzheimer's disease (AD) and do homeostatic failures lead to aberrant brain activity and memory decline, the overlapping phenotypes of AD and many other distinct neurodegenerative disorders? And finally, how do homeostatic systems operate in vivo under experience-dependent changes in firing rates and patterns? To target these questions, we have developed an integrative approach to study the relationships between ongoing spiking activity of individual neurons and neuronal populations, signaling processes at the level of single synapses and neuronal meta-plasticity. We will focus on hippocampal circuitry and combine ex vivo electrophysiology, single- and two-photon excitation imaging, time-resolved fluorescence microscopy and molecular biology, together with longitudinal monitoring of activity from large populations of hippocampal neurons in freely behaving mice. Utilizing these state-of-the-art approaches, we will determine how firing stability is maintained at different spatial scales and what are the mechanisms leading to destabilization of firing patterns in AD-related context. The proposed research will elucidate fundamental principles of neuronal function and offer conceptual insights into AD pathophysiology.

Mots-clés : homeostatic plastcity,synaptic transmission,short term plasticity,alzheimer s disease biology,electrophysiology,imaging
Projet ERC : BEE-MOVE (Horizon 2020, appel 2020, 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 : 1998856.0 €

How pollinators, such as bees, exploit plaHow pollinators, such as bees, exploit plant resources is a fundamental question in biology, with deep ecological, economical and societal consequences. When foraging on flowers, pollinators transfer pollen and mediate the reproduction of plants on which most animals (including us humans) rely on. Understanding the spatial foraging strategies and interactions of pollinators across the landscape is thus a critical scientific challenge to discover their influence on plant mating patterns and pollination efficiency. BEE-MOVE will use an interdisciplinary approach to mechanistically link pollinator movements to pollination efficiency at field scales, thereby crossing boundaries between research on pollinator behaviour and plant ecology. I will focus on two key pollinators worldwide: the buff-tailed bumblebee and the Western honey bee. 1) I will develop a new radar system to record and analyse the individual 3D movements of hundreds of bees foraging simultaneously. 2) I will use arrays of communicating radars and robotic plants to study how bees search and exploit food resources in field setups of several square kilometres, by manipulating key environmental factors such as the density of bees, the 3D distribution of plants, and the nutritional content of nectars and pollens. 3) From these observations, I will build computational agent-based models to investigate the influence of bee spatial strategies on pollination efficiency. Critical experiments will test model predictions in populations of natural plants. The dialogue between observations and simulations will create a positive feedback towards a robust, multi-level understanding of plant-pollinator interactions at the scale of landscapes. In addition to exploring entirely new grounds in pollination ecology, my results could be used to design practical interventions for conservation, sustainable agriculture and green development in the worrying context of pollinator declines.

Mots-clés : bumblebee,honey bee,behaviour,cognition,foraging,nutrition,movement ecology,computational modeling,pollination,radar,artificial flowers
Projet ERC : Ports (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Oslo — Pays : Norvège — Rôle : PI
Acronyme de l'entité : UiO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499950.0 €

How to study the turbulent transitions and risky mobilities of global capitalism today? An illuminating, but often overlooked site that lends itself to explorations into the changing nature of our economic system can be found at the interface between sea and city, i.e. at the port. Container ports have often been pushed to the edges of the urban spaces that they used to be centrally located in. A study on the city/sea-nexus will illuminate the dynamics behind the ways in which the center of global capitalism is currently on the move east-wards. This is not a uni-linear shift from “the West” to “the Rest”, but rather, is brought into existence by the nature of the ever-changing interplay between local territorialization and global connectedness. By investigating the relationship between port and city, PORTS will achieve three objectives: 1. to uncover the daily practices that port-related infrastructures enable in order to ensure the flow of commodities travelling through them; 2. to document the ways in which workers employed in the orbit of the port are affected by, and relate to, race-to-the-bottom-dynamics within the maritime world; and 3. to analyze the gradual move of the port away from the city center, and the urban waterfront changes that come with it, and how these are experienced, discussed, and justified by various stake-holders. PORTS will engage with local histories, unruly presents, and possible futures in four of the most important port-cities in the world: Singapore, Pusan (Korea), Rotterdam (Netherlands) and Piraeus (Greece). Through ethnographic work, it will clarify the changing nature of work, the significance of “place” as a site of accumulation and resistance, and the role of infrastructure for the inner workings of ports. Given the dearth of work addressing logistics-driven capitalism from an urban angle, this is the first study that systematically utilizes the ethnographic tool-kit to explore the economic frontier between city and sea.

Mots-clés : maritime studies,globalization,ports,labor,asia,containers,city
Projet ERC : CHROMONUMBER (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
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 : 599723.98 €

How variations in whole chromosome number impact organism homeostasis remains an open question. Variations to the normal euploid genome content are frequently found in healthy animals and are thought to contribute with phenotypic variability in adverse situations. Yet they are also at the basis of several human diseases, including neuro-developmental disorders and cancer. Our preliminary data shows that physiological aneuploidy can be identified in certain cells during development. Moreover, we have observed that when induced through mutations, non-euploid cells are effectively eliminated from the cycling population. A quantitative view of the frequency of non-euploid karyotypes and the mechanisms underlying their genesis is lacking in the literature. Further, the tissue specific responses at play to eliminate non-euploid cells, when induced through mutations are not understood. The objectives of this proposal are to quantitatively assess the occurrence of physiological chromosome number variations gaining insight into mechanisms involved in generating it. Additionally, we will identify the tissue-specific pathways involved in maintaining organism homeostasis through the elimination of non-euploid cells. We will use a novel genetic approach to monitor individual chromosome loss at the level of the entire organism, combine it with quantitative methods and state-of-the art-microscopy, and focus on two model organisms - Drosophila and mouse - during development and adulthood. We predict that the findings resulting from this proposal will significantly impact the fields of cell, developmental and animal physiology, generating novel concepts that will bridge the existing gaps in the field, and expand our understanding of the links between karyotype variations, animal development and disease establishment.

Mots-clés : aneuploidy,polyploidy,cell death,premature differentiation,stem cells,epithelial cells,tissue dependent responses,microcephaly,cancer
Projet ERC : EPICODE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : TU Dortmund University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1979679.0 €

Human DNA contains two types of biologically instructive information: the canonical nucleobases A, G, T, C, and the epigenetic nucleobases mC, hmC, fC, and caC. Canonical nucleobases encode the identity of all RNAs and proteins that are synthesized by a cell, whereas epigenetic nucleobases regulate this synthesis. This regulation shapes the phenotype of cells, and its perturbation is a key trigger of cancer. Canonical nucleobases can be decoded in a programmable manner by nucleic acids and their analogs via Watson-Crick-base pairing, and the simplicity of this recognition has enabled revolutionary developments in the biological sciences. In contrast, comparable developments in epigenetics have not yet been possible, since a molecular scaffold with programmable recognition of epigenetic nucleobases does not exist. We will establish the first class of molecules capable of the expanded programmable recognition of both canonical and epigenetic DNA nucleobases in vitro and in vivo. This is based on transcription-activator-like effectors (TALEs) that consist of four types of concatenated modules, each of which recognizes a canonical nucleobase. We have recently reported the detection of single epigenetic nucleobases by TALEs. In this project, we will 1. engineer a toolbox of TALE modules with selectivity for C, mC, hmC, fC, and caC, 2. employ them for TALE-based in vitro typing and profiling (reading) of cancer biomarker mC/hmC, and 3. design photoactivatable TALE-fusions that enable the writing and erasing of mC at user-defined genomic loci in vivo with spatiotemporal resolution. This will provide the first insights into the dynamic effects of de novo editing on chromatin regulation, and enables the imprinting of regulatory states. Given the central role of epigenetic nucleobases in cancer and the universality of our approach, this project will provide enabling and broadly applicable methodology for cancer epigenetics research, diagnosis and therapy.

Mots-clés : nucleic acid chemistry,dna recognition,chemical biology,directed evolution,optogenetics
Projet ERC : GREENT (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

Human activities have severe impacts on the biological carbon and nitrogen cycles. The most important consequences of these are global warming and water pollution. Wastewater treatment technology, in particular nitrogen removal systems, improved considerably in the last decade. The application of anaerobic ammonium oxidizing (anammox) bacteria in oxygen-limited granules has the potential to turn wastewater treatment plants into energy-efficient systems with minimal greenhouse gas emissions of carbon dioxide, nitrous oxide and methane. Recently, microorganisms that couple the anaerobic oxidation of methane to denitrification were discovered. An innovative integration of these microorganisms into partial nitritation-anammox systems for wastewater treatment offers an elegant and efficient solution to combat greenhouse gas emissions from wastewater treatment plants. The aim of the GREENT project is to determine nitrous oxide emissions from partial nitritation-anammox bioreactors and the parameters that govern these emissions, and to investigate the responsible pathways in molecular detail. Furthermore, I will explore the feasibility of an innovative bioreactor, which will remove ammonium and methane simultaneously through anammox and anaerobic methane-oxidizing microorganisms. This approach will turn the otherwise harmful methane into a resource for efficient nitrogen removal. These fundamental insights and technological advances will be achieved by a complimentary array of state-of-the-art methodology such as continuous culturing, stable isotope tracing and a combination of -omics methods together with physiological experiments and detailed measurements at full-scale installations. The results of this proposal will be of paramount importance for the wastewater treatment sector, but also indispensable for mathematical modelling, life cycle assessment and understanding the ecophysiology of the involved microorganisms.

Mots-clés : nitrogen removal,anaerobic ammonium oxidation,nitrogen cycle