The Ohi Lab

Laboratory of Cell Division

 

Third “M”: Motors.

Mitosis is a mechanical process requiring enzymes that are capable of doing work. Molecular motors such as kinesins and dynein use energy derived from ATP hydrolysis to perform various forms of work during cell division. Some motors move microtubules, enabling them to sculpt the mitotic microtubule array into various geometric configurations. Others move cargo. A third class of motors that fascinates us are those that modify microtubule dynamics. Kinesin-13s, for example, catalyze microtubule depolymerization. This unique property enables Kinesin-13s to set a length limit on microtubules (and thereby spindle length), destabilize erroneous kinetochore-microtubule attachments, and power polewards microtubule flux. More recently, we have focused on Kif18A, a human Kinesin-8 that also affects microtubule dynamics.





Fourth “M”: Microscopy. We believe that to know how something happened, you have to watch it take place. We observe chromosome and spindle dynamics in cells and Xenopus egg extracts, using biochemical or pharmacological perturbations to disrupt mitosis when needed. When possible, we attempt to reconstitute various aspects of mitosis in vitro, to simply reaction chemistry. This approach allows us to assign key aspects of spindle assembly and its dynamics to the activities of specific protein factors.

 



Much of our work can abbreviated in this way:




First “M”: Mitosis.

The process we study. Mitosis (meiosis in germ cells) divides a replicated set of chromosomes between two daughter cells. Life at both cell and organismal levels is not possible without precise chromosome segregation, and mistakes during this process can lead to human diseases ranging from birth defects to cancer.





Second “M”: Microtubules.

Chromosome segregation is carried out by a cellular machine called the mitotic spindle. Microtubules, filaments assembled from tubulin, are the building blocks of the spindle and move chromosomes by attaching specialized chromosomal sites termed kinetochores. The interface between kinetochores and microtubules is dynamic; kinetochore-attached microtubules undergo repeated cycles of assembly/disassembly without detaching. A major focus of the lab is to understand how this is possible, and additionally, uncover mechanisms that regulate kinetochore-microtubule dynamics.

The 4 M’s.

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Last modified: May 8, 2010

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