Role of microtubules in cell motility, with emphasis on the mechanism and regulation of dynein ATPase.
We are interested in the molecular mechanisms of cell motility with particular emphasis on the role of microtubules and associated motor proteins. Microtubules and associated proteins are responsible for a wide array of cellular functions such as ciliary and flagellar movement, transport of vesicles and other organelles in the cytoplasm of all cells, morphogenesis, and the proper segregation of chromosomes during mitosis and cell division.
We are using a variety of approaches to study the molecular motor dynein, a large molecular complex responsible for powering ciliary movement, cytoplasmic transport, assembly of the Golgi and chromosome movement. Questions include definition of dynein's molecular structure, mechanism, and regulation. Approaches include biochemical fractionation, analysis of macromolecular structure by new methods of electron microscopy, use of mutant strains of Chlamydomonas defective in dynein structure or assembly, and development of in vitro functional assays in which motility can be reconstituted from purified proteins. Currently, our focus is on the regulation of dynein by associated protein kinases and phosphatases.