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Resolving the mechanism of ciliary tip factors in primary and motile cilia assembly and function

Project description

Insight into cilia assembly and function

Cilia are conserved cell surface organelles composed of microtubules. They have diverse motility and sensory functions, and defects in their assembly lead to conditions known as ciliopathies. The EU-funded ResolvCiliaTip project will focus on the CCDC66 protein, a recently identified ciliary tip component implicated in progressive retinal degeneration, to provide insight into ciliary microtubule dynamics. Scientists aim to unveil the localisation and function of CCDC66, contributing to the improved characterisation of the causative genes of ciliopathies. Apart from providing fundamental knowledge, the project's results will lay the foundation for enhanced diagnostic approaches in future.

Objective

Cilia are conserved microtubule-based organelles, which extend from the cell surface and have diverse motility and sensory functions, integrating developmentally important signalling pathways. As such, defects in ciliary assembly and/or function can lead to developmental disorders and multi-systemic genetic diseases, termed ciliopathies. The ciliary tip, a region between microtubule ends and the ciliary membrane, is implicated in cilium assembly, disassembly, signalling, and motility. Few ciliary tip proteins identified so far are mutated in ciliopathies. Yet the complete identity of microtubule associated proteins at the ciliary tip of both primary and motile cilia, and the mechanisms underlying their regulation of ciliary microtubule dynamics and geometry, remain unknown. The proposed research will resolve the link between the ciliary tip geometry and function both in primary and motile cilia, as well as molecular mechanisms controlling the microtubule end dynamics at the ciliary tip and identify the full repertoire of ciliary tip components. The research will focus on functional characterization and interactions of the CCDC66 protein, which mutations cause progressive retinal degeneration, the most frequently observed phenotype across different ciliopathies. The CCDC66 is a recently identified tip component of the primary cilia and preliminary experiments suggest the axonemal and ciliary tip localization of CCDC66 in motile cilia. Therefore, we will investigate both the localization and function of CCDC66 at the primary and motile cilia tip with the nanometre-scale precision. We will elucidate the effect of CCDC66 on microtubule end dynamics using the biochemical assays and resolve the molecular proximity map of the CCDC66 using BioID method and proteomics. The results of this project, predicted to better characterize the causative genes of ciliopathies, could make positive impact on clinical studies and enhance diagnostic approaches in future.

Coordinator

KOC UNIVERSITY
Net EU contribution
€ 145 355,52
Address
RUMELI FENERI YOLU SARIYER
34450 Istanbul
Türkiye

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Region
İstanbul İstanbul İstanbul
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 145 355,52