Ciliary axonemes contain stable doublet microtubules (MTs) and stable triplet MTs are found in centrioles and basal bodies. Despite their importance, we know little of how stable MT-based structures are assembled, maintained, and disassembled. Because the same tubulin dimers assemble dynamic and stable MTs in most organisms, including the ciliate Tetrahymena thermophila, the different MT behaviors are attributed to associated proteins and protein modifications. In doublet and triplet MTs, some associated proteins are found inside the hollow MT; these microtubule inner proteins (MIPs) are the focus of our work. Originally discovered using various forms of electron microscopy, MIPs appeared as structures of unknown composition inside axonemal doublet microtubules. MIPs are proposed to mitigate the deformation and stress on doublet MTs caused by ciliary beating. Ciliary beating moves extracellular fluid in a single direction, which is necessary for many essential processes in humans. Defects disrupting motile cilia function cause a wide range of human pathologies, including Primary Ciliary Dyskinesia (PCD), hydrocephalus, and infertility in both sexes.
The Winey lab studies the role of MIPs and related proteins in basal bodies and cilia in the ciliate Tetrahymena, a tractable microbial system. Much of our current work centers on proteomic approaches to identifying MIP components and the structures of these components. We are also working to understand the role of these proteins through mutant analysis.