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CiliaTubulinCode

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Self organization of the cilium the role of the tubulin code

This project aims at understanding of the role of the tubulin code for self-organization of complex microtubule based structures. Cilia turn out to be the ideal structures for the proposed research. A cilium is a sophisticated cel... ver más

31/10/2024

FONDAZIONE HUMAN T...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

FONDAZIONE HUMAN TECHNOPOLE No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2024-10-31

ERC-2018-COG: ERC Consolidator Grant

I+D

Cerrada hace 6 años

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3 Participantes

FONDAZIONE HUMAN TECHNOPOLE

1.36M€ | Lider

INSTITUTO CARTUJA CORPORACIO...

MPG

630.87K€ | Participante

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Duración del proyecto: 68 meses Fecha Inicio: 2019-02-06
Fecha Fin: 2024-10-31

Líder del proyecto

FONDAZIONE HUMAN TECHNOPOLE No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto This project aims at understanding of the role of the tubulin code for self-organization of complex microtubule based structures. Cilia turn out to be the ideal structures for the proposed research. A cilium is a sophisticated cellular machine that self-organizes from many protein complexes. It plays motility, sensory, and signaling roles in most eukaryotic cells, and its malfunction causes pathologies. The assembly of the cilium requires intraflagellar transport (IFT), a specialized bidirectional motility process that is mediated by adaptor proteins and direction specific molecular motors. Work from my lab shows that anterograde and retrograde IFT make exclusive use of the B-tubules and A-tubules, respectively. This insight answered a long standing question and shows that functional differentiation of tubules exists and is important for IFT. Tubulin post-translational modifications (PTMs) contribute to a tubulin code, making microtubules suitable for specific functions. Mutation of tubulin-PTM enzymes can have dramatic effects on cilia function and assembly. However, we do not understand of the role of tubulin-PTMs in cilia. Therefore, I propose to address the hypotheses that the tubulin code contributes to regulating bidirectional IFT motility, and more generally, that the tubulin code is a key player in structuring complex cellular assembly processes in space and time. This proposal aims at (i) understanding if tubulin-PTMs are necessary and/or sufficient to regulate the bidirectionality of IFT (ii) examining how the tubulin code regulates the assembly of cilia and (iii) generating a high-resolution atlas of tubulin-PTMs and their respective enzymes. We will combine advanced techniques encompassing state-of-the-art cryo-electron tomography, biochemical imaging, fluorescent microscopy, and in vitro assays to achieve molecular and structural understanding of the role of the tubulin code in the self-organization of cilia and of microtubule based cellular structures.

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