Group of Intracellular Dynamics

Fig. 1: Spindle defects observed after mitotic gene RNAi in Drosophila S2 cells

This lab was founded in 2007.  Our research program has examined the cellular mechanisms of mitotic cell division, a critical process for cell proliferation and animal development. Defects in the regulation of cell division lead to various diseases, including cancer.   We have adopted multiple methodologies in order to understand mitosis, most notably high-resolution live cell microscopy and high-throughput, automated microscopy combined with genome-wide RNAi methods in animal cells.  We also utilize quantitative image analysis, computer simulation and mathematical modeling to understand how mitotic machineries quantitatively behave on a system level.   We recently completed a genome-wide RNAi screening of mitotic spindle/chromosome morphology in Drosophila cells, and identified over 200 genes that are required for mitosis in animals (Fig. 1).  Our research goal in the next decade is to dissect the molecular mechanisms underlying mitosis in animals and plants, focusing on the roles of the genes identified in the genome-wide RNAi screen.

Augmin: a protein complex required for microtubule generation within the spindle

Microtubules are nucleated at centrosomes, pre-existing microtubules and near chromosomes.  The importance of these pathways has been shown recently in several cell types, yet it is largely unknown how they are achieved at a molecular level.  Our genome-wide RNAi screen and extensive follow-up analyses identified an 8-subunit protein complex, “augmin”, that is required for centrosome-independent microtubule generation within the mitotic spindle (Goshima et al., 2007, 2008; Uehara et al., 2009). We anticipate that comprehensive analysis of this protein complex will help to build a global molecular picture of microtubule generation pathways within mitotic and meiotic spindles.

Reconstitution of mitosis in silico

Fig. 2:  Metaphase spindle in a cell (left) and in silico (right)

We wish to construct a quantitative mechanistic model of a dynamic mitotic structure, e.g., the spindle (Fig. 2; Goshima et al., 2005a, 2005b).  To achieve this, we will obtain a great deal of quantitative information on in vivo dynamics of mitotic proteins and phenotypes associated with their depletions.  We will then reconstitute spindle assembly and chromosome dynamics in silico.

Lab members