Research
We are interested in mechanisms that integrate the cell cycle, chromosome structure and gene expression to control cell differentiation. We combine genetic, molecular and biochemical approaches in yeast as our model organism. In one project we are examining the role of the Origin Recognition Complex (ORC), which controls both chromosome replication and chromatin-mediated transcriptional regulation. We want to understand how these two different roles of ORC are regulated.
In a second project, we are studying protein-protein interactions between ORC and the Sir1 protein. The Sir1 protein nucleates the assembly of specialized chromatin that represses transcription at only a few chromosomal positions. Interactions between the ORC and the Sir1 protein are confined to these positions. We want to understand what controls a Sir1p/ORC interaction, how this interaction is affected by the cell cycle and how it has evolved in fungal species.
In a third project, we are studying how two evolutionarily conserved DNA binding proteins, Fkh1 and Fkh2, regulate the cell cycle, silencing and a form of pseudohyphal differentiation associated with pathogenic yeast. Interestingly, Fkh proteins have roles in early development, cell-cycle progression and genetic diseases in humans. Studies in yeast should reveal insights by which these proteins function in humans.