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MiniBrain SIGNED

Cerebral Organoids: Using stem cell derived 3D cultures to understand human brain development and neurological disorders

Total Cost €

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EC-Contrib. €

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Partnership

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Project "MiniBrain" data sheet

The following table provides information about the project.

Coordinator
INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH 

Organization address
address: DR BOHRGASSE 3
city: WIEN
postcode: 1030
website: www.imba.oeaw.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 2˙800˙000 €
 EC max contribution 2˙800˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2021-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH AT (WIEN) coordinator 2˙800˙000.00

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 Project objective

Most of our knowledge on human development and physiology is derived from experiments done in animal models. While these experiments have led to a comprehensive understanding of the principles of neurogenesis, animal models often fall short of modelling many of the most common neurological disorders. Recent experiments have revealed characteristic striking differences in brain development between rodents and primates and may provide an explanation for this problem. The goal of this proposal is to use three dimensional organoid cultures derived from pluripotent human stem cells to reveal the human specific aspects of brain development and to analyse neurological disease mechanisms directly in human tissue. We have recently developed a 3D culture method allowing us to recapitulate human brain development during the first trimester of embryogenesis. Using this method, we will define the human specific brain patterning events in order to develop a culture system that can recapitulate essentially any part of the brain. Using a unique combination of cell type specific markers and mutagenic viruses, we will define the transcriptional networks defining specific neuronal subtypes. This will allow us to perform loss-of function genetics in human tissue to define transcription factors necessary for development of individual neuronal subtypes on a genome-wide level. Finally, we will apply the genome wide screening technology to human neurological disorders like microcephaly or schizophrenia to identify factors that can rescue disease phenotypes. This research proposal will provide fundamental insights into the cellular and molecular mechanisms specifying various neuronal subclasses in the human brain and establish technology that can be applied to a variety of cell types and brain regions. The proposed experiments have the potential to yield fundamental insights into human neurological disease mechanisms that can currently not be derived from animal models.

 Publications

year authors and title journal last update
List of publications.
2017 Ilka Reichardt, François Bonnay, Victoria Steinmann, Inga Loedige, Thomas R Burkard, Gunter Meister, Juergen A Knoblich
The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda
published pages: 102-117, ISSN: 1469-221X, DOI: 10.15252/embr.201744188
EMBO reports 19/1 2020-02-12
2018 Nina S. Corsini, Juergen A. Knoblich
Tracing Stem Cell Division in Adult Neurogenesis
published pages: 143-145, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.01.012
Cell Stem Cell 22/2 2019-06-13
2017 Madeline A Lancaster, Nina S Corsini, Simone Wolfinger, E Hilary Gustafson, Alex W Phillips, Thomas R Burkard, Tomoki Otani, Frederick J Livesey, Juergen A Knoblich
Guided self-organization and cortical plate formation in human brain organoids
published pages: 659-666, ISSN: 1087-0156, DOI: 10.1038/nbt.3906
Nature Biotechnology 35/7 2019-06-13
2018 Sebastian Wissel, Heike Harzer, François Bonnay, Thomas R. Burkard, Ralph A. Neumüller, Juergen A. Knoblich
Time-resolved transcriptomics in neural stem cells identifies a v-ATPase/Notch regulatory loop
published pages: jcb.201711167, ISSN: 0021-9525, DOI: 10.1083/jcb.201711167
The Journal of Cell Biology 2019-06-13
2018 Nina S. Corsini, Angela M. Peer, Paul Moeseneder, Mykola Roiuk, Thomas R. Burkard, Hans-Christian Theussl, Isabella Moll, Juergen A. Knoblich
Coordinated Control of mRNA and rRNA Processing Controls Embryonic Stem Cell Pluripotency and Differentiation
published pages: 543-558.e12, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.03.002
Cell Stem Cell 22/4 2019-06-13
2018 Shan Bian, Marko Repic, Zhenming Guo, Anoop Kavirayani, Thomas Burkard, Joshua A. Bagley, Christian Krauditsch, Jürgen A. Knoblich
Genetically engineered cerebral organoids model brain tumor formation
published pages: 631-639, ISSN: 1548-7091, DOI: 10.1038/s41592-018-0070-7
Nature Methods 15/8 2019-06-13
2018 Ilka Reichardt, François Bonnay, Victoria Steinmann, Inga Loedige, Thomas R Burkard, Gunter Meister, Juergen A Knoblich
The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda
published pages: 102-117, ISSN: 1469-221X, DOI: 10.15252/embr.201744188
EMBO reports 19/1 2019-06-13
2018 Lisa Landskron, Victoria Steinmann, Francois Bonnay, Thomas R Burkard, Jonas Steinmann, Ilka Reichardt, Heike Harzer, Anne-Sophie Laurenson, Heinrich Reichert, Jürgen A Knoblich
The asymmetrically segregating lncRNA cherub is required for transforming stem cells into malignant cells
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.31347
eLife 7 2019-06-13
2017 Joshua A Bagley, Daniel Reumann, Shan Bian, Julie Lévi-Strauss, Juergen A Knoblich
Fused cerebral organoids model interactions between brain regions
published pages: 743-751, ISSN: 1548-7091, DOI: 10.1038/nmeth.4304
Nature Methods 14/7 2019-06-13
2017 Magdalena Renner, Madeline A Lancaster, Shan Bian, Heejin Choi, Taeyun Ku, Angela Peer, Kwanghun Chung, Juergen A Knoblich
Self‐organized developmental patterning and differentiation in cerebral organoids
published pages: 1316-1329, ISSN: 0261-4189, DOI: 10.15252/embj.201694700
The EMBO Journal 36/10 2019-06-13
2017 Meritxell Huch, Juergen A. Knoblich, Matthias P. Lutolf, Alfonso Martinez-Arias
The hope and the hype of organoid research
published pages: 938-941, ISSN: 0950-1991, DOI: 10.1242/dev.150201
Development 144/6 2019-09-05

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