This work seeks to understand the internal responsible for the movements of flagella and cilia. These include the dynein-microtubule interaction responsible for active sliding, the oscillatory mechanism, and control mechanisms that determine a particular type of bending pattern and its parameters. Because of the importance of cilia and flagella in normal respiratory and reproductive functions (as evidenced by the pathology of """"""""immotile cilia syndromes""""""""), an understanding of the functioning of these organelles is important in its own right. In addition, simple flagella provide a particularly accessible and highly organized system that appears to be the best source of detailed information about microtubule mediated motility, which can be extended to increase our understanding of other systems such as mitosis, axonal transport, and the cross-bridge mediated sliding movement of actomyosin systems, including muscle. This work will utilize simple flagella such as those of sea urchin and tunicate spermatozoa and Chlamydomonas, which can be photographed with high spatial and temporal resolution to obtain detailed descriptions of the movement under a variety of conditions. Computer-assisted methods for analysis of these photographs will be extended. The work will emphasize functional dissection of the mechanisms of motility by observing the effects of exposing demembranated flagella to agents such as inhibitors, proteolytic enzymes, and specific antibodies, by observing the effects of removal and binding of flagellar components, and by analyzing the motility of mutant flagella of Chlamyodomonas. These experiments will provide information allowing us to identify and characterize the control mechanisms that operate in flagella, and will begin to provide information about the molecular components of these control mechanisms. Computer simulation methods will be used to interpret this imformation and to seek improved theoretical models for the generation of flagellar bending patterns.
