In order to divide, cells must first duplicate their entire contents and then segregate them into two daughter cells. The cell division cycle can be viewed as the ordered execution of a collection of duplication and segregation events, punctuated by physical division. Failure to perform these events in the proper order can be catastrophic for the cell and contributes to the genesis of diseases such as cancer. The focus of my lab is to elucidate the regulatory processes that ensure the program of duplication and segregation events occurs on schedule.
Early work in frog and marine invertebrate embryos suggested that cell-cycle events are controlled by a biochemical oscillator centered on a family of protein kinases called cyclin-dependent-kinases (CDKs). Using a variety of biochemical, molecular, genetic, genomic, and quantitative approaches, we have been investigating the role of CDKs play in controlling oscillations during the cell cycle. Specifically, we are interested in how the global program of cell-cycle transcription is regulated. Our findings suggest an interconnected network of transcription factors controls the temporal program of transcription and serves as an underlying cell-cycle clock. Using systems-levels approaches, we are investigating how this network oscillator functions to control cell division.
We have been addressing these questions using the budding yeast as a model system because of its experimental tractability and because the cell cycle machinery is highly conserved from yeast to human cells. Additionally, we have begun to expand our research into multi-cellular organisms.