Descrizione del progetto
Esaminare la formazione delle ciglia sulle cellule
Le ciglia sono organuli cilindrici presenti nelle cellule eucariote costituiti da microtubuli secondo un modello organizzativo definito mantenuto dal complesso di trasporto intraflagellare (IFT, IntraFlagellar Transport). Gli scienziati del progetto ciTTub, finanziato dall’UE, stanno lavorando sulla dissezione del meccanismo attraverso cui l’IFT fornisce elementi costitutivi e contribuisce all’omeostasi delle ciglia. Attraverso una combinazione di biochimica, cristallografia a raggi X e tecniche di microscopia crioelettronica a particella singola, ciTTub svelerà la biogenesi delle ciglia a risoluzione atomica, con importanti implicazioni per il trattamento di ciliopatie.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesmolecular biologystructural biology
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
8000 Aarhus C
Danimarca