Using Flies to Understand Mitotic Functions of Phosphoprotein Phosphatases

Vincent Archambault, PhD
Professor
Department of Biochemistry and Molecular Medicine
Université de Montréal
Institute for Research in Immunology and Cancer (IRIC)

This conference is hosted by David Hipfner, PhD. This conference is part of the 2024-2025 IRCM conference calendar.

About this conference
Dr. Vincent Archambault is a professor in the Department of Biochemistry and Molecular Medicine of Université de Montréal and a principal investigator at the Institute for Research in Immunology and Cancer. He obtained his PhD at the Rockefeller University in New York and conducted postdoctoral work at the University of Cambridge, UK. Research in Dr. Archambault’s lab aims to understand the molecular mechanisms controlling mitosis, with a particular focus on the roles of kinases and phosphatases. To this end, his team uses Drosophila and human cells in culture as model systems. Their research can help understand how defects in mitotic regulation contribute to cancer and suggest potential therapeutic targets.

About Vincent Archambault
A cell entering mitosis must undergo profound changes including chromosome condensation, nuclear envelope breakdown and spindle assembly. This transition is triggered by specific kinases that phosphorylate effector proteins to modify their activities. When the cell completes and exits mitosis, many of these substrates must be dephosphorylated to allow the emerging daughter cells to enter interphase. How phosphatases function to mediate this transition is still poorly understood. A few members of the Phosphoprotein Phosphatase (PPP) sub-family of Ser/Thr phosphatases, including PP1 and PP2A, are known to be strongly required for mitotic progression. In this seminar, I will present how my group uses a combination of genetic, biochemical, proteomic and imaging approaches in Drosophila as a model system to better understand how PPPs function and are regulated during mitosis. In particular, I will present our recent findings regarding the roles of PP2A in promoting the reformation of the nucleus at the end of mitosis, and how it relies on two regulatory subunits in this process. Finally, I will briefly show some of our early work in the characterization of the roles of additional PPPs in the regulation of other aspects of mitosis. Given the high degree of evolutionary conservation in the genes, proteins and mechanisms controlling mitosis, our findings are likely to be largely applicable to humans. As mitotic PPPs are recognized as potential drug targets to treat cancers and other diseases, a better mechanistic understanding of their functions could help future therapeutic developments.

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