Cell Division Dynamics Unit (Tomomi Kiyomitsu)
Cell division is a fundamental process in all organisms to create two daughter cells from a mother cell. During mitosis in eukaryotes, a microtubule-based structure called the mitotic spindle is assembled to segregate duplicated chromosomes into daughter cells. The bipolar nature of the spindle is critical for the accurate inheritance of genomic information. In addition, since the mitotic spindle positioning controls the distribution modes of polarized cell-fate determinants as well as the size and location of daughter cells, its positioning is critical to control daughter cell fates and tissue morphogenesis during the development of multi-cellular organisms.
In the Cell Division Dynamics unit, we are studying the mechanisms of bipolar spindle assembly, positioning, and their coordination in vertebrate mitosis using advanced cell-biological technologies. Based on our previous findings (see below), we are especially interested in how force-generating protein complexes are assembled and dynamically regulated by intrinsic and extrinsic signals to achieve proper spindle assembly and positioning for symmetric and asymmetric divisions.
We have mainly used symmetrically-dividing cultured human cells as a model. Recently, we are also using Medaka fish early embryos to reveal unidentified mechanisms of rapid spindle assembly and positioning in large early embryonic cells. We may also introduce other systems, such as mouse stem cells, to understand the roles of spindle positioning in self-renewal and differentiation.
We combine multiple advanced cell-biological technologies, including genome editing, multi-color live cell imaging, acute protein depletion (Tsuchiya et al., Current Biology 2021), and light-inducible protein manipulation (Okumura et al., eLife 2018). In addition, we will take advantage of OIST strengths, including high-end imaging and proteomics.
1. Tsuchiya K, Hayashi H, Nishina M, Okumura M, Sato Y, Kanemaki MT, Goshima G, Kiyomitsu T* Ran-GTP is non-essential to activate NuMA for spindle pole focusing, but dynamically polarizes HURP near chromosomes. Current Biology 31(1):115-127.e3. (2021)
2. Okumura M, Natsume T, Kanemaki MT, Kiyomitsu T* Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble. eLife doi: 10.7554/eLife.36559 (2018)
3. Natsume T, Kiyomitsu T, Saga Y, and Kanemaki MT* Rapid protein depletion in human cells by auxin-inducible degron tagging with short homology donors. Cell Reports 15(1):210-8. (2016)
4. Kiyomitsu T*, and Cheeseman IM* Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell 154(2):391-402. (2013)
5. Kiyomitsu T, and Cheeseman IM* Chromosome and spindle pole-derived signals generate an intrinsic code for spindle position and orientation. Nature Cell Biology 14(3):311-7 (2012)
1. Kiyomitsu T*, and Boerner S. The Nuclear Mitotic Apparatus (NuMA) Protein: A Key Player for Nuclear Formation, Spindle Assembly, and Spindle Positioning Frontiers in Cell and Developmental Biology 9:653801 (2021)
2. Kiyomitsu T* The cortical force-generating machinery: how cortical spindle-pulling forces are generated. Current Opinion in Cell Biology 60:1-8 (2019)
3. Kiyomitsu T* Mechanisms of daughter cell-size control during cell division. Trends in Cell Biology 25(5):286-295. (2015)
*Positions for postdocs and graduate students are OPEN!*
We are looking for motivated postdocs and graduate students who would like to join us on our quest to unravel the basic mechanisms of cell division with cutting-edge technologies.
Please feel free to contact us (e-mail: tomomi.kiyomitsu[at]oist.jp) if you are interested.