2007 Award Winner Dr. Mónica Bettencourt-Dias Instituto Gulbenkian de Ciência, Oeiras, Portugal

Appointment at time of winning the Award
Group Leader, Instituto Gulbenkian de Ciência, Oeiras, Portugal

Abstract
Our research is focused on the regulation of cell proliferation, with an emphasis on the centrosome, the primary microtubule organizing centre in animal cells. Problems with centrosomes and its core structures, the centrioles, are associated with a variety of human diseases, from cancer to infertility. The formation of these structures is highly regulated. They duplicate once every cell cycle, with one centriole, the “daughter”, forming close to an already existing one, the “mother”, so that their number remains stable. To provide new perspectives on cell proliferation we screened by RNAi all the protein kinases from fruit flies. Amongst several novel players, we identified SAK/PLK4, a kinase implicated in tumourigenesis. We showed in flies and humans that SAK/PLK4 is essential for centriole duplication. Strikingly, SAK/PLK4 can trigger centriole formation in the absence of a mother, i.e, de novo, showing the mother centriole is not a bona-fide “template” in daughter formation. Instead, it is a platform for recruitment of regulatory molecules, such as SAK/PLK4, hence triggering the assembly of daughter centrioles close by. This work suggests misregulation of centriole duplication regulators may generate some of the centrosome abnormalities observed in cancer. In that case, those molecules may be used in the diagnostic, prognostic and as targets in cancer treatment.