Starter Grant: Spatial Control of Mitosis by Septins

Dartmouth College, Hanover NH

Investigators

Abstract

Dr. Gladfelter will investigate how cell division is regulated spatially by septins in cells with several nuclei. For these studies, a multinucleated, filamentous fungus called Ashbya gossypii in which nuclei divide asynchronously is used. Asynchronous nuclear division enables cells to restrict responses to external environmental signals in a spatial manner. Septins, which are conserved, filament-forming proteins that assemble into cortical rings, appear to function in A. gossypii nuclear division by establishing mitosis promoting zones in the cell. Preliminary data demonstrates that nuclei divide near septin rings in A. gossypii and that the spatial pattern of nuclear division is disturbed in cells lacking septins. Thus, the septins appear to give spatial directions to nuclei that determine the position of division. A. gossypii septins assemble into a variety of morphologically distinct organizations and it is unclear whether all septin structures in the cell can promote mitosis and in which phase of the nuclear cycle septins act. Dr. Gladfelter hypothesizes that septins accelerate progression through G2 of the division cycle and that only a subset of septin structures have the power to direct mitosis. To test these hypotheses, the dynamics of nuclear division and changes in septin organization will be observed simultaneously in living cells using time-lapse microscopy. Strains will be generated in which components of the septin ring, the spindle pole body (SPB, fungal centrosome) and the nucleus are labeled with different fluorescently tagged proteins to detect septins and nuclear division progression in individual cells. These experiments will define how morphologically distinct septin structures arise and mature and how the kinetics of nuclear progression depends upon the presence of different septin organizations. The results of these experiments will provide a foundation for studying both the mechanisms of septin ring assembly in multinucleated cells and the basis for how the septins communicate with the cell cycle machinery. Broader Impacts: This work will be performed with the assistance of undergraduate woman at Dartmouth College who participate in the Woman In Science Program (WISP).