Descripción del proyecto
Sigue el ritmo: una mejor visión de la estructura y función de los cilios
Los cilios son orgánulos de forma capilar que se mueven como las espigas de trigo al viento. Tanto si actúan de forma autónoma para impulsar organismos unicelulares o en grandes números para impulsar líquido en nuestros pulmones y cerebro, estos osciladores mecánicos presentan una dinámica y unas estructuras microtubulares complejas. La punta de los cilios es un componente esencial y se encuentra entre los más desconocidos. El proyecto financiado con fondos europeos SILIA está desarrollando una técnica microscópica que contribuirá a conocer mejor la estructura de la punta y el ensamblaje de cilios. Los datos sobre la estructura se evaluarán en el contexto de todas las proteínas relacionadas con la punta y, mediante una reconstrucción experimental, permitirá comprender mejor la función de dicha punta.
Objetivo
Cilia and flagella are evolutionary conserved organelles indispensable for vital processes in eukaryotic organisms, such as environment sensing, cell motility, signaling and development. Broad spectrum of ciliary functions, together with omnipresence of the cilium throughout human body, explains the range of symptoms associated with congenital ciliary disorders called ciliopathies. On the other hand, cilia are essential for survival of parasites, such as trypanosomatids, in the host. Therefore, cilia are of great interest as a potential therapeutic target.
The ciliary tip is an essential ciliary domain; it provides capping and mechanical stabilization of the ciliary cytoskeleton, it is a turning point of the intraflagellar transport trains, a sole place of cilium growth and a place of budding of signaling vesicles. Yet the tip is the most enigmatic of all ciliary domains, with structures constituting the ciliary tip largely unknown. This hampers our understanding of how are the tip-related processes brought about and orchestrated.
To gain insight into the dynamic ultrastructure od the ciliary tip, I will develop a novel technique for cryogenic correlative light and electron microscopy based on solid immersion lens (SIL) optics. I will integrate the resulting imaging data with the tip proteome project project carried out by the host lab and provide mechanistic understanding of the resulting tip model by employing top-down synthetic biology and in vitro reconstitution approaches.
Key achievements of this project will include: (i) development of the cryo-SIL technique and (ii) unraveling the functions of the the ciliary tip domain, which will broaden our knowledge of the principles of self-organization of biological systems.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
142 20 Praha 4
Chequia