Cell Cycle Regulation
Cell division is a crucial process for the development, survival and reproduction of all organisms. The events of cell division are coordinated by a complex molecular network that is largely conserved across species. Errors in this coordination can lead to unrestricted proliferation or chromosome segregation defects, two hallmarks of cancer. We use the fruitfly Drosophila melanogaster as a model to study the molecular pathways operating during cell cycle progression.
Regulation of the Polo kinase in the cell cycle
We are currently interested in the regulation of the Polo kinase, a central coordinator of mitosis and cytokinesis. Polo regulates the mitotic functions and behavior of chromosomes and centrosomes, and the cytokinetic machinery by phosphorylating many crucial targets. The human counterpart of Polo, Polo-like kinase 1, is deregulated in many cancers and is the target of anti-cancer drugs in development. We have recently identified novel molecular mechanisms regulating the Polo kinase during the cell cycle in the fly. These involve protein interactions and phosphorylation events. We are working to characterize these pathways and understand their implications for cell division and development.
Pathways directing mitotic entry and exit
Another, emerging axis of research in our group is the regulation of mitotic entry and exit. Recent work by us and others has uncovered a crucial pathway whereby the Greatwall kinase is responsible for the inhibition of Protein Phosphatase 2A at mitotic entry. This results in the accumulation of the phosphorylated forms of the mitotic substrates of Cycin-Dependent Kinase 1. Conversely, the phosphatase must become active again to allow exit from mitosis and completion of cell division. These pathways are conserved in humans and are currently of particular interest since blocking mitotic entry and exit constitute means to interfere with cancer cell proliferation and survival. Several important questions must now be addressed before we can reach a full understanding of this regulation and identify the best therapeutic targets.
Our research unit uses a multidisciplinary approach combining molecular biology, genetics, biochemistry, proteomics, functional genomics and microscopy to gain a better molecular understanding of cell cycle control and cell division. We are keen to explore how the cell cycle machinery is integrated in the different tissues of the whole animal, but we also take advantage of cultured cells from both Drosophila and humans.