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REMIND SIGNED

Targeting pathological synaptic pruning by microglia in neurodegeneration

Total Cost €

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EC-Contrib. €

0

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.

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

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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