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MiniBRAIN SIGNED

Investigating the pathogenic mechanisms underlying TUBB2B-related brain malformations using induced pluripotent stem cells and cerebral organoids.

Total Cost €

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EC-Contrib. €

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Partnership

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 MiniBRAIN project word cloud

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

mutation    subsequently    isogenic    stemming    figure    cortical    leaders    imp    line    investigation    brains    abnormal    migration    division    david    functional    knoblich    cortex    mts    microscopy    underlying    close    lab    employ    cas9    preliminary    expressed    hypothesis    severe    mechanisms    self    phenotypes    proliferation    cerebral    mechanism    structural    perform    recapitulate    reputable    scientific    cycle    crispr    mt    aggregated    keays    generate    genotypes    roles    cell    suggests    dr    imba    data    controls    cells    technologies    hosted    gene    differentiated    pioneers    communication    malformations    dynamics    immunohistochemistry    organoid    embryonic    global    tubb2b    pathogenic    cos    neural    microtubules    editing    lineage    genome    elucidate    examine    organisation    wild    disorders    patients    techniques    vienna    neuronal    normal    stem    mutations    human    tubulin    community    impaired    mini    organising    pluripotent    brain    ipscs    highlights    co    disease    fibroblasts    neurogenesis    mutant    me    certain    encodes   

Project "MiniBRAIN" data sheet

The following table provides information about the project.

Coordinator
FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH 

Organization address
address: CAMPUS-VIENNA-BIOCENTER 1
city: WIEN
postcode: 1030
website: www.imp.ac.at

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 Austria [AT]
 Total cost 166˙156 €
 EC max contribution 166˙156 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH AT (WIEN) coordinator 166˙156.00

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 Project objective

Mutations in TUBB2B are associated with a range of malformations of cortical development: severe structural brain disorders stemming from abnormal cerebral cortex formation. Functional investigation of TUBB2B mutations will enable us to elucidate distinct pathogenic mechanisms underlying various malformations and advance our understanding of normal brain development. TUBB2B is highly expressed during embryonic brain development. It encodes a major component of microtubules (MTs), which perform essential roles during neuronal proliferation, neuronal migration and cortical organisation. I have obtained preliminary data in non-neuronal cells that suggests certain (but not all) TUBB2B-related malformations result from impaired cell division during neurogenesis. This highlights a potential disease-specific mechanism. I will investigate this hypothesis using state-of-the-art induced pluripotent stem cells (iPSCs) and cerebral organoid (COs) technologies, more relevant to brain development. I will generate iPSCs from fibroblasts obtained from patients with specific TUBB2B genotypes and brain phenotypes. I will use CRISPR/Cas9 genome editing to generate isogenic controls (in addition to a generic wild type line). Mutant and control iPSCs will be differentiated into a neural lineage to study effects of mutations on cell cycle and MT dynamics. Subsequently, differentiated cells will be aggregated into COs; self-organising ‘mini-brains’ that recapitulate human brain development and disease. I will employ immunohistochemistry and microscopy to examine TUBB2B mutation effects on neuronal proliferation, migration and organisation. I will hosted by Dr David Keays (IMP, Vienna). His lab are global leaders in tubulin-gene research and work in close collaboration with the pioneers in CO techniques (Knoblich Lab, IMBA, Vienna). Dissemination and communication of results will impact the scientific community, promote EU-based research and establish me as a reputable figure in the field.

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

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