Grant: Project Grant

Most physiological processes in cells are regulated by enzymes known as protein kinases. These enzymes act by adding a small negative charge on proteins, a phosphate group. A large fraction of cancers are caused by misregulation of protein kinases. We propose to study the role of two families of protein kinase known as Polo-like kinases (PLKs) and cyclin-dependent kinases (CDKs), which are strongly associated with cancer development in humans. We have developed a novel way to precisely modulate the activity of CDK and PLK in living cells. This will allow us to identify all the proteins that CDK and PLK modify by phosphate addition during the process of cell division. We will perform this experiment at very high temporal resolution -in the scale of minutes- while cells divide to determine which proteins are favourite targets of CDK and PLK, and which ones are low priority targets for these kinases. We will achieve this objective by using a combination of genetic and biochemical experiments in a model organism. Ultimately, this project will identify which targets of CDK and PLK are more crucial for the process of cell division, and how misregulation of these "high priority" targets can lead to cell division errors and cancer formation.