Vincent Archambault and his team study the molecular mechanisms that regulate the cell division cycle, with a focus on mitosis. Defects in this process can contribute to the production and aberrant proliferation of cancer cells.
Cell division is essential for the development, survival and reproduction of all living species. At each cycle, the cellular components, including chromosomes, must be synthesized and segregated accurately as one cell becomes two cells. This process requires the coordination of several intracellular events by a network of enzymes that has emerged early in the evolution of eukaryotes. Defects in the functions of these enzymes can lead to chromosome segregation errors or excessive cell divisions, which promote the development of cancer.
To understand the molecular mechanisms of cell division, the Archambault lab uses Drosophila as a model organism, as well as cells in culture from Drosophila and human origins. Their multidisciplinary approach combines genetics, molecular biology, biochemistry, chemical biology and various types of microscopy, including live imaging. New mechanisms identified in Drosophila are generally conserved in humans.
The team is particularly interested in the spatiotemporal mechanisms that control mitotic entry and mitotic exit. As a cell enters mitosis, it condenses its chromosomes, breaks its nuclear envelope, and assembles a mitotic spindle onto which chromosomes attach. These events require the coordinated activities of several kinase enzymes including Polo, Greatwall and Cdk1. As the cell completes (exits) mitosis, chromosomes are segregated and the two emerging cells reassemble a nuclear envelope, decondense chromosomes, disassemble the spindle and separate by cytokinesis. These events require other enzymes such as the Anaphase-Promoting Complex and phosphatases, including PP2A-B55. To modify their substrates in an orderly manner, mitotic enzymes communicate with each other and undergo dramatic changes in localization during cell division.
The Archambault lab aims to identify the most crucial substrates of key mitotic enzymes and to determine how the substrates’ modifications translate into physical changes operating during cell division. Another goal is to decipher how mitotic enzymes are themselves regulated in time and in the intracellular space, and how this regulation serves their functions. This fundamental knowledge of cell biology may serve as a basis for the development of new treatments that interfere with the division of cancer cells.