Research projects
This lab was founded in April 2007. Our research program has examined the cellular mechanisms of mitotic cell division, a critical process for cell proliferation and animal development, defects in which lead to various diseases such as cancer. Our research has adopted multiple methodologies 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 utilized quantitative image analysis, computer simulation and mathematical modeling to understand how mitotic machineries quantitatively behave on a system level. We have 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). My research goal in the next decade is to dissect the molecular mechanism underlying mitosis, focusing on the role of the genes identified in the genome-wide RNAi screen.
Fig. 1: Spindle defects observed after mitotic gene RNAi in Drosophila
S2 cells
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 (Fig. 2).
Fig. 2: Model for the augmin- and γ-TuRC (γ-tubulin ring complex)-dependent microtubule amplification within the mitotic spindle
Reconstitution of mitosis in silico
We wish to construct a quantitative mechanistic model of a dynamic mitotic structure such as the spindle (Fig. 3; Goshima et al., 2005a, 2005b). To do this, we will obtain a lot 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.
Fig. 3: Metaphase spindle in a cell (left) and in silico
(right)