Comprendre et cibler la régulation spatiotemporelle de la division cellulaire

 

Vincent Archambault

Université de Montréal

 

Domaine : cancer

Programme Chercheurs-boursiers - Senior

Concours 2018-2019

Cancer is a family of diseases caused by excessive proliferation of cells in the human body. Research in my laboratory aims to understand the molecular mechanisms that control cell division. Mutations in genes and proteins that participate in these mechanisms induce cancer. We use the fly Drosophila as a model. This organism allows the use of powerful experimental approaches combining genetics, biochemistry, molecular biology and microscopy to accelerate discovery. Since the molecular mechanisms that control cell division are strongly conserved between species, our findings generally apply to humans and can lead to the identification of new therapeutic avenues.

In order to divide, a cell must coordinate important transformations in chromosomes and other intracellular structures. These processes are triggered by enzymes that chemically modify other proteins to change their activities. We have contributed to the discovery of a new module of enzymes that is essential for this coordination. In a first axis of research, we aim to understand how changes in localization of these enzymes (Greatwall and PP2A-B55) enable them to control different intracellular structures and compartments.  Another goal is to identify the proteins that are modified by these enzymes and to understand in details the resulting effects on the molecular mechanisms at play during cell division.

In a second axis, we are studying the mechanisms that coordinate the activity and localization of another enzyme that is essential for cell division (Polo). Discovered in the fly, this protein is already recognized as a therapeutic target for several cancers. In this part, we are also looking to identify genes whose inactivation makes cancer cells more sensitive to chemical inhibitors of Polo. The results obtained will help better understand the cellular functions of Polo and could help design therapeutic strategies that combine Polo inhibitors with inhibitors of other enzymes that function with Polo.