description): This research will define the molecular template of ciliary and flagellar microtubules. These organelles are essential for the development and survival of species from protozoa to humans, where they function in the propulsion of protozoa and sperm, and in epithelial transport of embryonic morphogens, cerebrospinal fluid, and tracheal and oviduct contents. Cilia also function in the chemo-/mechano-receptors, retinal photoreceptors, acoustico-vestibular systems, and olfactory neurons. Cilia, flagella, and their parent organelles, centrioles and basal bodies are constructed of an evolutionarily axoneme of doublet and triplet microtubules: these tubules contain specialized sets of protofilaments, termed ribbons, composed of tektins, tubulin and other proteins. Based on the molecular details of tektins and ribbons, the applicant proposes the original hypothesis that this ribbon structure forms a fundamental template for the assembly of centrioles, basal bodies, cilia and flagella. This hypothesis will be tested using the biflagellate Chlamydomonas reinhardtii system, in which the functions of ribbon proteins will be analyzed by a combined application of genetics, protein chemistry, and structural analysis of mutants. One gene/protein, RIB43a/rib43a with homologues in trypanosomes and humans is already under analysis.
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