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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.

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

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

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 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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