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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.

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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.
fax: n.a.

 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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