Feedbacks between mechanics, geometry and polarity sorting ensures rapid and precise mitotic spindle assembly
Presented by Professor Alex Mogilner
Courant Institute and Department of Biology, New York University
One of the most fundamental cell biological events is assembly of the mitotic spindle – molecular machine that segregates sister chromatids into two daughter cells in the process of cell division. Two existent models of the mitotic spindle assembly are 1) search-and-capture (SAC) and 2) acentrosomal microtubule assembly (AMA). SAC model is pleasingly simple: microtubules (MTs), organized into two asters focused at two centrosomes, undergo dynamic instability: they grow and shrink randomly, rapidly and repeatedly. As soon as a growing MT end bumps into a kinetochore (KT) – molecular complex in the middle of a sister chromatid – the connection between the spindle pole (centrosome) and this chromatid is established. This model predicts that KTs are captured at random times and that slow spindle assembly is plagued by errors. For decades, the SAC model seemed to work. Our data ruins the SAC model and suggests that a hybrid between SAC and AMA models could work. I will explain how we used 3D tracking of centrosomes and KTs in animal cells to develop a computational agent-based model, which explains the remarkable speed and precision of the almost deterministic process of the spindle assembly emerging from random and imprecise molecular events.
Prof. Alex Mogilner received M.Eng. degree in Engineering Physics in 1985 from the Ural Polytechnic Institute. He received PhD degree in Physics from the USSR Academy of Sciences in 1990. He did research in Mathematical Physics until 1992, when he started studying Mathematical Biology at the University of British Columbia. After receiving PhD degree (adviser Leah Edelstein-Keshet) in Applied Mathematics from UBC in 1995, Alex worked at UC Berkeley with George Oster as a postdoctoral researcher, and in 1996 he came to the Math Department at the University of California at Davis as an Assistant Professor. He became an Associate professor in 1999, and in 2002 he became a Professor at the Department of Mathematics and Department of Neurobiology, Physiology and Behavior at UC Davis. Since 2014, Dr. Mogilner is a Professor of Mathematics and Biology at Courant Institute and Department of Biology at the New York University. Alex’s areas of expertise include Mathematical Biology, Cell Biology and Biophysics; he does research on mathematical and computational modeling of cell motility, cell division and galvanotaxis. Alex published about 130 papers in high impact journals including Nature, Science, PNAS. He developed models of keratocyte motility, polymerization ratchet, and search-and-capture mechanism of spindle assembly. His research is/was supported by NIH and NSF grants, Army Office of Research and by United States-Israel Binational Science Foundation. Alex served on editorial boards of many journals including Cell, Biophysical Journal, Current Biology, Journal of Cell Biology, Bulletin of Mathematical Biology, Molecular Biology of the Cell. He gave plenary talks and organized many international conferences on mathematical biology and cell biophysics, and taught at many summer schools. Dr. Mogilner was a panel chair at NIH. Multiple news and views were published about his scientific discoveries.