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Self-organization of the cilium: the role of the tubulin code

Objective

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.

Field of science

  • /medical and health sciences/basic medicine/pathology
  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /social sciences/social and economic geography/transport
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

ERC-2018-COG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Address
Hofgartenstrasse 8
80539 Muenchen
Germany
Activity type
Research Organisations
EU contribution
€ 1 986 406

Beneficiaries (1)

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany
EU contribution
€ 1 986 406
Address
Hofgartenstrasse 8
80539 Muenchen
Activity type
Research Organisations