Faculty Research

One of the hallmarks of cancer cells is loss of control of cell division, and understanding the regulators of cell division is essential to understanding the nature of cancer. The main focus of work in my laboratory is to understand the molecular and genetic mechanisms that control cell division. Since these mechanisms are highly evolutionarily conserved, cell division can be studied in lower organisms such as yeast and other fungi, and the findings can then be used to understand cell division in higher organisms, including humans. My laboratory uses two fungi, the budding yeast Saccharomyces cerevisiae and the fungus Aspergillus nidulans, to identify and characterize genes and proteins that control cell division, particular mitotic entry, and exit. We are currently studying a gene in yeast, Kin3, which is a poorly understood member of the NIMA family of mitotic regulators. Using high-throughput robotics and molecular techniques, we have screened the entire budding yeast genome to identify genes that interact with Kin3, as part of an ongoing study to reveal genes and cellular processes that Kin3 affects. We are also studying two genes in Aspergillus nidulans which were originally identified in our laboratory and which are involved in regulating cell division. Mutation of one of these genes causes a lethal interaction with a mutation in nimA, the Kin3 homolog of Aspergillus nidulans and the first identified member of this mitotic regulatory family. These studies should lead to a better understanding of the mechanisms that control cell division in these organisms.

Dr. Bernadette Connors

Disruption of the orderly progression of cell cycle events often leads to unrestrained cell growth and predisposition to cancer. Research into the molecular mechanisms that regulate these processes is consequently of great medical and scientific interest. In the budding yeast Saccharomyces cerevisiae, DBF4 and CDC7 encode the regulatory and catalytic subunits of the conserved eukaryotic Dbf4-dependent kinase (DDK), respectively. Although levels of Cdc7p remain constant through the cell cycle, Dbf4p is an unstable protein whose levels peak at the onset of S phase and are maintained until late mitosis, after which the protein is ubiquitinated and ultimately proteolyzed. The carefully timed degradation of Dbf4p and other cell cycle-regulated proteins limits DNA replication to once per cell cycle. I am taking both a genetic and biochemical approach to understand the regulated proteolysis of Dbf4p and selected mitotic proteins in this organism. Current efforts include examining protein-protein interactions among chosen mitotic proteins and known regulators of proteolysis, as well as an assessment of the genetic interactions among these same regulators.