Our laboratory is interested in how cell cycle signals regulate chromosome segregation and polarized morphogenesis. Our experimental approaches include a combination of biochemical, genetic and live-cell imaging. There are ongoing projects using both yeast and animal cell systems.
One area of interest for the laboratory is the mechanism of anaphase B. Many of the proteins involved in anaphase have been identified through genetic screens. One conserved component of the central spindle identified in our laboratory has been purified and its in vitro properties are being characterized. The goal of this work is to understand how the half spindles are held together and how the spindle is disassembled at the end of mitosis. A related project concerns the regulation of spindle function by the cyclin degradation machinery (anaphase promoting complex or APC). Several spindle proteins are degraded through the APC at different times during the cell cycle. We are working on the mechanisms regulating the timing of these degradation events.
A second area of interest is how polarity factors determine the position of the spindle within the cell. Spindle position is regulated during the development of many organisms in order to generate asymmetric cell divisions. Establishing spindle position involves capture of astral microtubules by poorly defined cortical proteins. Through genetic screens we have identified cortical cytoskeletal proteins and G-protein regulators necessary for determining spindle position. We hope to develop a mechanistic understanding of this process by studying the biochemical interactions between these proteins. In addition, a recently described cell cycle checkpoint monitors the successful positioning of the spindle in yeast. Work is in progress to define how the cell recognizes abnormal spindle position and communicates this information to cell cycle regulators.