B-Cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast

Our group is broadly interested in understanding the biological clock mechanisms that control the timing of events during the cell division cycle. In 2008, the Haase group proposed a new model in which a complex network of sequentially activated transcription factors regulates the precise timing of gene expression during the cell-cycle, and functions as a robust time-keeping oscillator. Greater than a thousand genes are expressed at distinct phases of the cycle, and the control network itself consists of ~20 components, so this dynamical system is far too complex to understand simply by biological intuition. We rely heavily on the expertise of the Harer group (Dept. of Mathematics, Duke University) for the analysis of complex data, and their understanding of dynamical systems.  Using a collection of tools, including molecular genetics, genomics, mathematical models, and statistical inference, our groups aim to understand how the cell division clock works, how it might be perturbed in proliferative diseases such as cancer, and how the clock components might be targeted for new anti-tumor therapies.  Qualitatively, the clock networks that control the yeast cell cycle look much like the networks controlling circadian rhythms in a variety of organisms. More recently, we have been using our experimental and quantitative approaches to investigate the function of circadian clocks, as well as clocks that control the division and development of pathogenic organisms such as P. falciparum and P. vivax, the causative agents of malaria.