Description du projet
Décortiquer la formation de cils dans les cellules
Les cils sont des organites cylindriques présents dans les cellules eucaryotes. Ils sont composés de microtubules organisés selon une configuration définie, maintenue par le complexe de transport intraflagellaire (IFT pour «intraflagellar transport»). Les scientifiques du projet ciTTub, financé par l’UE, entendent décortiquer le mécanisme selon lequel l’IFT fournit des composants fondamentaux et contribue à l’homéostasie du cil. En combinant des techniques de biochimie, de cristallographie à rayons X et de cryomicroscopie de particule unique, ciTTub dévoilera la biogenèse du cil à résolution atomique et aura d’importantes implications pour le traitement des ciliopathies.
Objectif
Cilia are essential hair-like structures presented at the surface of eukaryotic cells that allow motility, fluid flow and complex inter- and intracellular signalling events. Nine pairs of microtubules organized in a cylindrical shape called axoneme form the backbone of cilia. The formation and maintenance of cilia is dependent on a multi-subunit protein complex termed the intraflagellar transport (IFT) complex that actively delivers axonemal building blocks such as tubulin from the base to the tip of growing cilia. Lack of cilia or its miss-construction leads to severe developmental diseases called ciliopathies. Despite its fundamental role in cilium biogenesis, the process of tubulin recruitment, loading and unloading by the IFT machinery remains poorly understood. In this proposal, I aim to elucidate the mechanism of tubulin loading onto IFT complexes by determining high-resolution structures of intraflagellar transport (IFT) complexes bound to tubulin. Details about the IFT-tubulin interaction interface will be obtained by a combination of biochemical techniques like site directed photo- and chemical crosslinking followed by mass-spectrometry analysis and the structural biology techniques X-ray crystallography and single particle cryo-electron microscopy (cryo-EM). Ultimately, this study will enrich our understanding of cilium biogenesis and homeostasis by providing the first insight at atomic resolution into cargo selection and loading onto IFT machinery.
Champ scientifique
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesmolecular biologystructural biology
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
8000 Aarhus C
Danemark