Descripción del proyecto
Disección de la formación de cilios en las células
Los cilios son orgánulos cilíndricos presentes en las células eucariotas compuestos de microtúbulos situados en un patrón organizativo definido, mantenido por el complejo de transporte intraflagelar. Los científicos del proyecto financiado con fondos europeos ciTTub están trabajando en la disección del mecanismo por el que el complejo de transporte intraflagelar proporciona componentes y contribuye a la homeostasis de los cilios. Mediante el uso de una combinación de bioquímica, cristalografía de rayos X y técnicas de microscopía crioelectrónica de partículas individuales, ciTTub desvelará la biogénesis y resolución atómica de los cilios con implicaciones importantes para el tratamiento de ciliopatías.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesmolecular biologystructural biology
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
8000 Aarhus C
Dinamarca