Research Unit

Cell Cycle Regulation

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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.

Research topic

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.

Research objectives

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.

  • Vincent Archambault

    Principal Investigator, Cell Cycle Regulation Research Unit, IRIC

Research topics

Research team

  • Vincent Archambault


    Principal Investigator, Cell Cycle Regulation Research Unit, IRIC

  • Laura Chastant


    Ph.D.. Student

  • Virginie Émond-Fraser


    M.Sc. Student

  • Marine Guelle


    Ph.D Student

  • Jingjing Li


    Ph.D. Student

  • Karine Normandin


    Research Officer

Publications

  • August 28, 2023

    Genetic enhancers of partial PLK1 inhibition reveal hypersensitivity to kinetochore perturbations.

    Normandin K, Coulombe-Huntington J, St-Denis C, Bernard A, Bourouh M, Bertomeu T, Tyers M, Archambault V
    PLoS Genet 2023-08-28 ;19( 8 ):e1010903

  • July 1, 2023

    Identification of PP2A-B55 targets uncovers regulation of emerin during nuclear envelope reassembly in Drosophila.

    Emond-Fraser V, Larouche M, Kubiniok P, Bonneil E, Li J, Bourouh M, Frizzi L, Thibault P, Archambault V
    Open Biol 2023-07-01 ;13( 7 ):230104

  • April 1, 2022

    The spindle assembly checkpoint and the spatial activation of Polo kinase determine the duration of cell division and prevent tumor formation.

    Gallaud E, Richard-Parpaillon L, Bataillé L, Pascal A, Métivier M, Archambault V, Giet R
    PLoS Genet 2022-04-01 ;18( 4 ):e1010145

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News

  • September 6, 2023

    KIF18A: a promising anticancer target for combinatorial therapy with PLK1 inhibitors

    The PLK1 kinase is involved at multiple levels in the control of cell division. Cancer cells are often particularly dependent on the activity of this enzyme. However, the anticancer therapies developed to target PLK1 remain largely ineffective to date. The laboratory of Professor Vincent Archambault, Director of IRIC’s Cell Cycle Regulation Research Unit, collaborated with the laboratory of Professor Michael Tyers, then Director of IRIC’s Systems Biology and Synthetic Biology Research Unit, to better understand the cellular functions of PLK1 and to identify genes whose inactivation interferes with cell proliferation in synergy with existing PLK1 inhibitors. The results suggest that inhibition of the kinesin KIF18A could be a therapeutic avenue to exploit in combination with PLK1 inhibitors. Published in the journal PLOS Genetics, the study was led by research advisor Karine Normandin.

  • August 1, 2023

    Identification of the Emerin protein as a target of the PP2A-B55 phosphatase: a key regulation for mitosis exit

    IRIC’s Cell Cycle Regulation Research Unit and Proteomics and Mass Spectrometry Research Unit, headed respectively by Professors Vincent Archambault and Pierre Thibault, have taken advantage of the fruit fly Drosophila melanogaster to identify PP2A-B55 target proteins. Their results reveal that the nuclear envelope protein Emerin is dephosphorylated by PP2A-B55, a regulation event that is important for nuclear envelope reformation and embryonic development. Conducted jointly by doctoral students Virginie Emond-Fraser and Myreille Larouche, the study is published in the Royal Society‘s Open Biology journal.

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