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REMIND SIGNED

Targeting pathological synaptic pruning by microglia in neurodegeneration

Total Cost €

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EC-Contrib. €

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Partnership

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 REMIND project word cloud

Explore the words cloud of the REMIND project. It provides you a very rough idea of what is the project "REMIND" about.

correlate    goals    prunining    advantage    assays    multidisciplinary    metabolic    brain    mediate    genetically    genetic    reveal    synapses    resolution    strategies    dysfunctional    degradation    validating    pathological    labelling    nanobodies    responsible    extensive    generating    link    cas9    diseases    drugs    summary    intense    disorders    literature    encoded    association    phagocytosis    combination    characterisation    ex    little    signature    pathology    generate    causal    editing    vivo    remind    impairment    neurodegenerative    implicate    microglial    neurodegeneration    techniques    synapse    pruning    genes    players    transcriptomics    underlying    shaper    expressed    majority    variants    mechanisms    remodelling    cutting    microscopy    function    molecular    super    cognitive    microglia    introducing    cells    edge    alone    pathogenesis    mediated    poorly    synaptic    asses    genome    combining    vitro    disease    crispr    proteomics    risk    indicates    models    suggests    mouse   

Project "REMIND" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE DE LAUSANNE 

Organization address
address: Quartier Unil-Centre Bâtiment Unicentre
city: LAUSANNE
postcode: 1015
website: www.unil.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 1˙499˙991 €
 EC max contribution 1˙499˙991 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-STG
 Funding Scheme ERC-STG
 Starting year 2019
 Duration (year-month-day) from 2019-01-01   to  2023-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE DE LAUSANNE CH (LAUSANNE) coordinator 1˙499˙991.00

Map

 Project objective

Synapse loss is the major correlate of cognitive impairment in many neurodegenerative diseases. Recent literature suggests that microglia, which mediate synaptic pruning during brain development, can be responsible for synapse loss in neurodegeneration. Although the underlying mechanisms are poorly understood, growing evidence indicates that dysfunctional microglia affect synapses number and function in pathology. Genome-wide association studies reveal that the majority of risk genes associated with neurodegenerative disorders are highly expressed in microglia. While such studies clearly implicate these cells in the pathogenesis of the disease, little is known about the causal mechanisms that link microglial risk variants to loss of synapses. We will identify the molecular mechanisms involved in microglia-mediated synapse loss. We will also generate novel in vitro and ex vivo models of ‘risk microglia’, by introducing genetic variants associated with cognitive impairment –alone or in combination- specifically in microglia, taking advantage of CRISPR/ Cas9 genome editing techniques. These goals will be achieved by combining cutting-edge transcriptomics and proteomics with mouse models of intense synaptic remodelling, to reveal the unique molecular signature of ‘shaper microglia’. A multidisciplinary approach will allow the extensive characterisation of risk models, by combining metabolic analysis, synaptic phagocytosis and degradation assays, with super-resolution microscopy, and novel genetically encoded labelling methods. With the knowledge generated here, we aim at developing and validating in vivo novel drugs- and nanobodies-based approaches for effective targeting of pathological pruning. In summary, REMIND will focus on: 1) Identifying molecular players in microglial-mediated synapse loss 2) Generating ‘risk microglia’ models, to asses the role of genetic variants associated with neurodegeneration 3) Developing novel strategies for targeting prunining

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The information about "REMIND" are provided by the European Opendata Portal: CORDIS opendata.

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