Molecular mechanisms of cytokinesis
Cell division is a fundamental and universal process that is essential for all development. It occurs in a two-step process: first, during mitosis, duplicated sets of chromosomes move to opposite poles of the cell; second, during cytokinesis, the cell physically splits into two cells each containing one set of chromosomes. Scientists have been observing cytokinesis for over a century and have long proposed that defects in the process give rise to cancer. However, we are only beginning to understand how cytokinesis is regulated at the molecular level.
The long-term aim of our lab is to understand how cytokinesis normally occurs, and how its dysfunction can promote cancer. Ultimately, this will lead to better cancer treatments.
Cytokinesis requires the formation of a dynamic actin- and myosin-based structure, the contractile ring, which forms beneath the plasma membrane at the cell equator during anaphase. Constriction of this ring pulls the plasma membrane into the cell interior during cleavage furrow ingression. The contractile ring then hands over the job of holding the plasma membrane to another more stable structure called the midbody ring, which is where the plasma membrane must ultimately pinch off to generate two distinct cells. Our current research efforts are centered on understanding how the midbody ring derives from the contractile ring, as we know very little about this process which is vital to the success of cytokinesis.
We use cultured cells from the fruitfly, Drosophila melanogaster, as a model system. These cells are extremely sensitive to RNA interference, allowing us to inactivate genes at will. Previously, this allowed us to define the set of genes required for cytokinesis in a genome-wide RNAi screen. S2 cells are also ideally suited to high-resolution video-microscopy and are easily transfected to generate stable lines expressing fluorescent versions of proteins of interest. Using this system, we have uncovered many important insights into how cytokinesis is regulated.
Developmental control of cytokinesis
Although all cells divide by cytokinesis, they do not all do so in the same manner in the context of a developing organism. For example, a stem cell divides asymmetrically to ensure that one of the daughter cells remains a stem cell while the other follows its appropriate developmental fate.
We would like to understand how the core cytokinetic machinery is differentially regulated to suit the needs of different developmental contexts. There exist many developmentally regulated variations of cytokinesis and these are particularly well described in Drosophila. We are beginning to explore cytokinesis in these in vivo contexts using high-resolution microscopy and the powerful genetic tools available for Drosophila.