NeuroCentro
Financiado
Novel mechanisms of neurogenesis from centrosome to engineering migration
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 centros...
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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Duración del proyecto: 64 meses
Fecha Inicio: 2020-05-06
Fecha Fin: 2025-09-30
Fecha Fin: 2025-09-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-05-06
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-ADG:
ERC Advanced Grant
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUN...
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Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
195.04K€ |
Participante