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ORGANOMICS SIGNED

Reconstructing human cortex development and malformation with single-cell transcriptomics

Total Cost €

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EC-Contrib. €

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Partnership

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 ORGANOMICS project word cloud

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

transcriptomes    interdisciplinary    quantitative    platform    networks    hierarchies    transcriptomic    transcriptome    hybridization    trace    malformations    dissect    vision    revolutionizing    decisions    tracing    mosaic    neurodevelopmental    resolve    transition    scrna    brain    genetic    lineage    expression    seq    analyze    types    models    sequence    seqfish    counterparts    perform    patients    cas9    aberrations    create    network    extended    situ    technologies    individual    composition    regulate    gene    differentiation    innovations    underlying    entirely    screens    cortex    cell    fluorescence    protocols    crispr    mechanisms    corticogenesis    cerebral    genotypes    cells    integrative    dimensional    progenitor    organ    provides    organomics    throughput    groundbreaking    trees    quantify    recapitulate    cortical    output    alterations    tissues    stem    generate    organoids    function    probabilities    label    knockout    understand    cellular    strategy    parallel    organoid    modelled    generation    genes    reconstruct    direction    human    vitro    diseases    single    coupled    resolution    thousands    reconstructions    measuring    infer    barcoding    sequential   

Project "ORGANOMICS" data sheet

The following table provides information about the project.

Coordinator
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH 

Organization address
address: Raemistrasse 101
city: ZUERICH
postcode: 8092
website: https://www.ethz.ch/de.html

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
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 Coordinator Country Switzerland [CH]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-01-01   to  2022-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH CH (ZUERICH) coordinator 1˙171˙787.00
2    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) participant 328˙212.00

Map

 Project objective

Technologies to sequence single-cell transcriptomes (scRNA-seq) are revolutionizing our ability to analyze cell composition and differentiation in complex tissues. In parallel, recent innovations allow the generation of three-dimensional tissues from stem cells that recapitulate human development. In this proposal, we will focus on human cortex development modelled by cerebral organoids. Our vision is to create an integrative single-cell transcriptomic platform to reconstruct cerebral organoid development, and dissect network alterations that lead to human brain malformations. Our project will be advanced through the following objectives:

1. Single-cell transcriptome-coupled lineage tracing: We will use cellular barcoding to label individual cortical progenitor cells, trace their output and lineage trees with high-throughput scRNA-seq, and quantify lineage transition probabilities between cell types.

2. Gene knockout screens in mosaic organoids: We will use CRISPR/Cas9 to perform genetic screens of up to 100 genotypes in mosaic organoids to understand mechanisms that regulate cell lineage decisions during cortex development.

3. High-throughput reconstructions of cortex malformations: We will generate cerebral organoids from patients with cortical malformations and reconstruct networks and infer differentiation hierarchies using high-throughput and lineage-coupled scRNA-seq. We will spatially resolve network aberrations using sequential fluorescence in situ hybridization (seqFISH).

ORGANOMICS provides an entirely new quantitative direction to study human corticogenesis. We will build high-resolution models of cortex development by measuring the expression and function of genes in thousands of single cells. Our interdisciplinary project will lead to groundbreaking insight into mechanisms underlying neurodevelopmental diseases. Our general strategy can be extended to various other organ systems where protocols to generate in vitro counterparts can be established.

 Publications

year authors and title journal last update
List of publications.
2018 J. Gray Camp, Damian Wollny, Barbara Treutlein
Single-cell genomics to guide human stem cell and tissue engineering
published pages: 661-667, ISSN: 1548-7091, DOI: 10.1038/s41592-018-0113-0
Nature Methods 15/9 2020-01-16
2019 Johannes Klaus, Sabina Kanton, Christina Kyrousi, Ane Cristina Ayo-Martin, Rossella Di Giaimo, Stephan Riesenberg, Adam C. O’Neill, J. Gray Camp, Chiara Tocco, Malgorzata Santel, Ejona Rusha, Micha Drukker, Mariana Schroeder, Magdalena Götz, Stephen P. Robertson, Barbara Treutlein, Silvia Cappello
Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia
published pages: 561-568, ISSN: 1078-8956, DOI: 10.1038/s41591-019-0371-0
Nature Medicine 25/4 2020-01-16

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