The Wordeman lab studies an unusual class of Kinesin-related Motor proteins: the Kinesin-13 Family or Microtubule Depolymerizing Kinesins. This family comprises 3 unique genes in mammals: Kif2A, Kif2B and Kif2C/MCAK or Mitotic Centromere Associated Kinesin. Our research ranges from structural and molecular mutational analysis, in vitro live imaging to cellular and developmental behavior especially during cell division. The big picture is to understand how microtubule behavior is regulated to modulate cell shape, cell division and cell motility. Wait a few seconds for the movies to load.

A Mitotic HeLa cell expressing GFP-MCAK which has been mutated by Yulia Ovechkina to be inactive with respect to microtubule depolymerization. The advantage of the mutant form is that it gives us a rough idea of the localization of the protein during mitosis without interfering with microtubule dynamics or cell division at low levels of expression. The mitotic spindle is approximately 12 microns in length pole to pole. This movie* was made in collaboration with George von Dassow at the Center for Cell Dynamics at Friday Harbor Labs. George is presently located at the Oregon Institute of Marine Biology.

*Journal of Cell Biology (2005) 169:391-397.
D

MCAK tracking on the ends of astral microtubules regulates their length as depletion of MCAK protein results in long astral microtubules and a startling loss of spindle position as described in Kathleen Rankin's recent cover paper in the Journal of Cell Biology (2010) 190:35-43.

This phenomenon is the subject of a JCB biosights profile.

Below is a mitotic HeLa cell depleted of MCAK protein and expressing GFP-Myosin II (green) and Cherry-tubulin (red). Once it is loaded click on the movie to play it from the beginning.

X
In addition to investigating the cellular function of MCAK which involves the regulation of microtubule length and error correction during chromosome segregation. We also study the behavior and properties of single MCAK molecules using Total Internal Reflection Fluorescence (TIRF) microscopy in vitro:

Below you will see a field of stabilized microtubules in red. GFP-MCAK and ATP flows in and the microtubules will begin to shorten from both ends due to the depolymerizing activity of MCAK. The shimmer you see is due to the diffusion of single GFP-MCAK molecules on the microtubule lattice.

Imaging is performed on a custom total internal reflection microscope built by Jeremy Cooper who also developed the methods for preparing microscope slides which exhibit extrememly low background. These microtubules are on average 2 microns in length and the movie plays at 100x real time.

Read Jeremy's recent review. Read Jeremy's recently published paper.