Research


Mitosis and Spindle Dynamics

Dr. Chuanhai Fu

Dr Fu, Chuanhai (符传孩)

Assistant Professor, Department of Biochemistry

BSc, BEng, PhD (USTC)

Contact
Email: chuanhai@hku.hk
Tel: (852) 2819 9208
Office: L3-80, Laboratory Block, 21 Sassoon Road, Hong Kong

Research Opportunities:

We are currently seeking highly motivated postgraduate students to join our research team. Applicants with expertise in molecular biology are particularly welcome. Please contact Dr. Fu Chuanhai directly with your CV and a description of your previous research experience.

Postgraduate Research Projects Available:

  • Characterization of a novel microtubule plus end tracking protein ase2p.
  • Purification and identification of spindle associated proteins.

Research Description:

Mitosis is a fundamental process of life. During mitosis, chromosomes are precisely segregated and equally divided into two daughter cells. Mitosis errors can give rise to chromosome segregation defects, leading to more severe problems such as genomic instability, birth defects and cancer. Proper chromosome separation depends upon a polarized microtubule array: the spindle. The spindle changes morphologically and dynamically throughout mitosis to suit the needs of different mitotic events. The spindle forms and becomes bipolar during prophase for chromosome capture; it stays at a relatively steady length at metaphase for chromosome alignment; and it elongates rapidly during anaphase B for chromosome segregation (Figure 1A).

Our laboratory is interested in understanding the fundamental molecular mechanisms underlying spindle and chromosome dynamics during mitosis. We combine yeast genetics, quantitative live-cell imaging, biochemical and cell biological approaches to dissect organization, dynamics and regulation of the spindle in the fission yeast Schizosaccharomyces pombe and mammalian cells. Our current studies focus on:

  1. Identification of spindle proteins
    We have previously identified a novel kinesin klp9p, which is responsible for driving spindle elongation during anaphase B , and a microtubule associated protein ase1p, which serves as a microtubule bundler for organizing the spindle midzone (Figure 1B). To identify other proteins that participate in regulating spindle dynamics, we are conducting genetic screens for yeast mutants that display spindle defects. In addition, we are developing proteomics-based biochemical approaches for purification and identification of spindle associated proteins.
  2. Regulation of spindle dynamics
    Kinases and phosphatases lies at the heart of regulatory networks. Fission yeast has three core mitotic kinases: Plo1p/Polo, cdc2p/CDK1 and ark1p/Aurora-B and one clp1p/CDC14 phosphatase. They play critical roles in regulating many aspects of spindle dynamics. We have previously developed an in vitro assay for detecting kinase and phosphatase substrates. Using this in vitro assay, we are testing novel kinase and phosphatase substrates.

Figure 1 for Reseach Interest: Mitosis in fission yeast

Figure 1. Mitosis in fission yeast S. pombe. (A) A cartoon depicts spindle organization at prophase, metaphase and anaphase B; (B) Time-lapse images of cells expressing mCherry-atb2p (a-tubulin) and GFP tagged proteins (ase1p, klp9 and mis12p).

Publications, Achievements, and Grants:

Selected Publications:

  • Fu C†, Jain D, Costa J, Velve-Casquillas G, Tran PT†. 2011. Mmb1p binds mitochondria to dynamics microtubules. Curr Biol 21:1431-39 (†, co-corresponding author)
  • Velve-Casquillas G, Fu C, Le Berre M, Cramer J,  Meance S, Plecis A, Baigl D, Greffet JJ, Chen Y, Peil M, Tran PT. 2011. Fast microfluidic temperature control for high resolution live cell imaging. Lab Chip 11(3):484-9
  • Zhang L, Shao H, Huang Y, Yan F, Chu Y, Hou H, Zhu M, Fu C, Aikhionbare F, Fang G, Ding X, Yao X. 2011. PLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity. J Biol Chem 286(4): 3033-46
  • Fu C, Ward JJ, Loiodice I, Velve-Casquillas G, Nedelec FJ, Tran PT. 2009. Phospho-regulated interaction between kinesin-6 Klp9p and microtubule bundler Ase1p promotes spindle elongation. Dev Cell 17: 257-67
  • Liu J, Wang Z, Jiang K, Zhang L, Zhao L, Hua S, Yan F, Yang Y, Wang D, Fu C, Ding X, Guo Z, Yao X. 2009. PRC1 cooperates with CLASP1 to organize central spindle plasticity in mitosis. J Biol Chem 284: 23059-71
  • Fu C†, Yan F†, Wu F, Wu Q, Whittaker J, Hu H, Hu R, Yao X. 2007. Mitotic phosphorylation of PRC1 at Thr470 is required for PRC1 oligomerization and proper central spindle organization. Cell Res 17: 449-57 (†, co-first author)
  • Janson ME, Loughlin R, Loiodice I, Fu C, Brunner D, Nedelec FJ, Tran PT. 2007. Crosslinkers and motors organize dynamic microtubules to form stable bipolar arrays in fission yeast. Cell 128: 357-68
  • Fang Z, Miao Y, Ding X, Deng H, Liu S, Wang F, Zhou R, Watson C, Fu C, Hu Q, Lillard JW, Jr., Powell M, Chen Y, Forte JG, Yao X. 2006. Proteomic identification and functional characterization of a novel ARF6 GTPase-activating protein, ACAP4. Mol Cell Proteomics 5: 1437-49
  • Xue Y, Zhou F, Fu C, Xu Y, Yao X. 2006. SUMOsp: a web server for sumoylation site prediction. Nucleic Acids Res 34: W254-7
  • Fu C†, Ahmed K†, Ding H, Ding X, Lan J, Yang Z, Miao Y, Zhu Y, Shi Y, Zhu J, Huang H, Yao X. 2005. Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3. Oncogene 24: 5401-13 (†, co-first author)
  • Jin C, Zhang Y, Zhu H, Ahmed K, Fu C, Yao X. 2005. Human Yip1A specifies the localization of Yif1 to the Golgi apparatus. Biochem Biophys Res Commun 334: 16-22
  • Yao J†, Fu C†, Ding X, Guo Z, Zenreski A, Chen Y, Ahmed K, Liao J, Dou Z, Yao X. 2004. Nek2A kinase regulates the localization of numatrin to centrosome in mitosis. FEBS Lett 575: 112-8 (†, co-first author)
  • Zhou R, Watson C, Fu C, Yao X, Forte JG. 2003. Myosin II is present in gastric parietal cells and required for lamellipodial dynamics associated with cell activation. Am J Physiol Cell Physiol. 285: C662-73.