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CELLPHASE_AD SIGNED

Genetics to understand cellular components of Alzheimer Disease pathogenesis

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 CELLPHASE_AD project word cloud

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

establishes    crisper    provides    neuron    expressed    validate    patient    worldwide    patients    engineered    manipulate    bioinformatics    understudied    expression    pathology    extensive    classically    models    genes    insights    first    single    answer    stem    accelerated    rodent    vitro    hypotheses    translation    limitations    pathogenesis    explore    phenotypes    astroglia    generate    versatile    gt    putative    progression    inflammation    isogenic    centric    therapies    makeup    lines    validating    vivo    human    context    transplanted    mouse    polygenic    population    drug    influences    chimeric    microglia    risk    dynamic    mice    arm    transcriptomics    ad    cholesterol    600    cas9    disease    mechanistic    tau    possibilities    followed    cells    humanized    axis    inducible    complexity    genetic    wild    platform    alzheimer    scores    pathological    linked    view    profiles    genomic    cell    largely    genetics    beta    ips    capture    health    brain    time   

Project "CELLPHASE_AD" data sheet

The following table provides information about the project.

Coordinator
VIB 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

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 Belgium [BE]
 Total cost 2˙374˙997 €
 EC max contribution 2˙374˙997 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-ADG
 Funding Scheme ERC-ADG
 Starting year 2019
 Duration (year-month-day) from 2019-11-01   to  2024-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB BE (ZWIJNAARDE - GENT) coordinator 2˙374˙997.00

Map

 Project objective

Alzheimer disease (AD) is a major health problem worldwide. New therapies require an accelerated translation of genetic information into mechanistic insights. Given limitations of rodent models, fully humanized models are needed to capture the complexity of the disease process. Human stem cells (iPS) provide great possibilities but are largely investigated in vitro with associated limitations. Many of the novel genetic risk factors for AD are expressed in microglia and astroglia, which remains an understudied population in this classically neuron-centric field. We propose here mouse-human chimeric mouse models to test the effects of AD-associated genetic risk factors on the phenotypes of transplanted microglia and astroglia derived from patients and from genomic engineered, isogenic stem cells. The cells will be followed during disease progression in brain of wild type and of mice developing Aβ- and Tau- pathology. Using single cell transcriptomics, a dynamic view of the cell states over time is generated. In a first arm of the project, we investigate how the genetic makeup of patient derived stem cells with high and low polygenic risk scores influences pathological cell states. In the second arm of the project, we generate inducible Crisper/CAS9 iPS isogenic cell lines to manipulate rapidly and specifically the expression of 4 selected AD associated genes linked to a putative cholesterol pathway but also affecting inflammation. These cell lines will be used also in the second phase of the project when validating hypotheses generated from the extensive bioinformatics analysis of the 600.000 single human cell profiles generated. We expect to identify and validate >5 novel drug targets in the astroglia-microglia axis of AD pathogenesis. Our work provides humanized models for AD, an answer on how genetic makeup affects microglia and astroglia in an AD relevant context, and establishes a highly versatile platform to explore human genetics in human cells in vivo.

 Publications

year authors and title journal last update
List of publications.
2019 Renzo Mancuso, Johanna Van Den Daele, Nicola Fattorelli, Leen Wolfs, Sriram Balusu, Oliver Burton, Adrian Liston, Annerieke Sierksma, Yannick Fourne, Suresh Poovathingal, Amaia Arranz-Mendiguren, Carlo Sala Frigerio, Christel Claes, Lutgarde Serneels, Tom Theys, V. Hugh Perry, Catherine Verfaillie, Mark Fiers, Bart De Strooper
Stem-cell-derived human microglia transplanted in mouse brain to study human disease
published pages: 2111-2116, ISSN: 1097-6256, DOI: 10.1038/s41593-019-0525-x
Nature Neuroscience 22/12 2019-12-16

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