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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.

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

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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