CORDIS
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CORDIS

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Novel mechanisms of neurogenesis- from centrosome to engineering migration

Project information

Grant agreement ID: 885382

Status

Grant agreement signed

  • Start date

    1 October 2020

  • End date

    30 September 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 256 834

  • EU contribution

    € 2 256 834

Hosted by:

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH

Germany

Objective

The centrosome is a crucial cellular organelle involved in many functions especially during development where it acts to regulate key processes, such as cell division, cilia formation and migration. While many mutations in centrosome-associated proteins lead to diseases often predominantly affecting the brain, the basis for this specificity is in most cases not known. Likewise, basic aspects of centrosome biology, such as the role of RNAs at the centrosome, are largely unknown. Our recent discovery of novel centrosome-associated proteins in human neural stem cells revealed specific RNA-binding proteins at the sub-distal appendages of centrosomes with significant and selective associations to periventricular heterotopia (PH), a neuronal migration disorder. This provides a unique entry point to explore, in the first part of this project, fundamental questions associated with the role of RNAs and RNA-binding proteins at the centrosome and their contribution to neurodevelopmental disorders. In the second part, we will explore changes in centrosome composition from NSCs to young migratory neurons and identify the role of the centrosome in neuronal subtype-specific migration modes using the novel centrosome protein Akna as entry point. In the third part, we will utilize our advanced tools for dCas9 multiplexed transcriptional engineering to restore centrosome function of ectopic neurons and revert migration defects causing PH. These rescue attempts will be extended to later stages of development aiming to revert differentiated glia, the ependymal cells, to radial glial cells, that serve as guides for migrating neurons. This work will thus tackle fundamental functions of neural-specific centrosome proteins, laying the basis to understand the brain-specific phenotype of mutations in factors that are widely expressed but predominantly affect the brain.
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Host institution

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH

Address

Ingolstadter Landstrasse 1
85764 Neuherberg

Germany

Activity type

Research Organisations

EU Contribution

€ 2 256 834

Beneficiaries (1)

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH

Germany

EU Contribution

€ 2 256 834

Project information

Grant agreement ID: 885382

Status

Grant agreement signed

  • Start date

    1 October 2020

  • End date

    30 September 2025

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 256 834

  • EU contribution

    € 2 256 834

Hosted by:

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH

Germany