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The research in our laboratory is concerned with the mechanism and regulation of microtubule polymerization and the roles of microtubule polymerization dynamics in cell function. Microtubules are major structural components of the cytoskeleton in cells that function in the development and maintenance of cell shape and in a variety of kinds of cellular movements. They are composed of a heterodimeric building block protein known as tubulin, and also have associated with their surfaces and ends a wide variety of proteins, known as microtubule-associated proteins (or MAPs), which function to regulate the polymerization dynamics of the microtubules and to mediate the functional interactions of microtubules with other cell components. Microtubules are not simple equilibrium polymers. Rather, the energy released by the hydrolysis of GTP to GDP when tubulin adds to the microtubule ends gives rise to growing and shortening phase transitions at the microtubule ends (called dynamic instability). In addition, at polymer mass steady state the growing and shortening transitions at one end of a microtubule give rise to net growing, while the growing and shortening transitions at the opposite end of the microtubule gives rise to net shortening (called treadmilling or flux). Our work is aimed at understanding the mechanism and the regulation of microtubule polymerization dynamics in relation (a) to chromosome movements during mitosis, and (b) to the formation and function of the asymmetric axonal and dendritic processes of nerve cells. One of our major recent efforts has been to understand how a number of specific MAPs from neuronal cells (the Tau proteins and MAP2) modulate and perhaps regulate microtubule polymerization dynamics. Another major thrust of our work has been to elucidate the molecular mechanisms of action of a number of antimitotic antitumor drugs, such as vinblastine and taxol, which act by modulating the dynamics of tubulin addition and loss at microtubule ends, and to use the drugs as research tools to elucidate the roles of microtubule polymerization dynamics in mitosis. |
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