Primary cilium is an antenna – like organelle present on a surface of most cells. Whilst it was originally described as vestigial organelle and hence largely neglected, recent years have indisputably proven its status as a seminal structure for sensing various extracellular stimuli. In vertebrates, primary cilium governs many important aspects of embryonic development as well as tissue homeostasis in adulthood. Given that, it is not surprising that a numerous human diseases, known as ciliopathies, have been directly related to defects in assembly of primary cilia. Thus, full understanding of the biology of primary cilia is of interest for basic as well as more clinically oriented research.
Here we propose a research plan centered on elucidation of the molecular mechanisms and consequences of initial steps of the assembly of primary cilium, with focus on events controlled by critical regulator of ciliogenesis, Tau tubulin kinase 2 (TTBK2). The proposed project pursues two main goals: first, we will perform proteomic screens in order to uncover binding partners of TTBK2 as well as protein-protein interactions dependent of TTBK2 activity. Second, we will use a combination of biochemical and cell biology approaches to characterize mutual molecular interactions and interdependencies between components of cilium assembly pathway, with specific focus on the elucidation of mechanisms controlling activity of TTBK2 and identification and characterization of relevant TTBK2 substrates.
We expect that our findings will contribute to reveal some of the crucial molecular mechanisms of primary cilium assembly and their functional consequences, which may have extension to clinical applications.

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