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Microtubule Self-Assembly

Speaker: David Odde, University of Minnesota
Series: CBE Departmental Seminars
Location: Elgin Room (E-Quad A224)
Date/Time: Wednesday, March 12, 2014, 4:00 p.m. - 5:00 p.m.

Microtubule assembly dynamics are vital to many cellular processes, including nerve growth and cell division. In the current textbook view of microtubule assembly, ??-tubulin subunits add efficiently to growing microtubules with minimal subunit loss during growth. This view has also led to the view that the GTP cap that stabilizes is small, perhaps as little as a single layer of GTP tubulin subunits at the growing microtubule tip. In this lecture, I will review how new ultra-high resolution measurements, combined with computational modeling, led to a major revision of this picture. In particular, our studies revealed that microtubule assembly is inefficient, with extensive subunit loss during overall growth, and subunit on-off dynamics are far more rapid than previously appreciated (by about a factor of 10). These findings (Schek and Gardner et al., Current Biology, 2007; Gardner et al., Cell, 2011) led us to re-examine the basic mechanisms of how microtubule-directed anticancer drugs, such as paclitaxel and vinblastine, influence microtubule assembly. In the coming years, our hope is that we will come to understand how these widely prescribed drugs exert their influence on microtubules, and from this understanding eventually design next generation anticancer therapeutics.