Prigent Group Research

One of the most fascinating events during cell cycle is when the cell distributes its genetic material to its two daughter cells and divides. This stage, called mitosis, is a tightly controlled and highly regulated process, and any defect can trigger chromosome instability and lead to cancer. At the G2/M transition the cell activates a number of protein kinases required to progress faithfully through mitosis. Their catalytic activity is maximal when chromosomes are aligned on the metaphase plate, and drops at the anaphase onset while protein degradation increases. During these events the cell also coordinately prepares itself for the most critical stage of its life, cytokinesis, the physical separation of the two daughter cells that involves a breakage of the plasma membrane. In the group we study the mechanisms that regulate these different aspects of mitosis. We are particularly interested in the main mitotic structures, which are the centrosomes, the mitotic spindle and the chromosomes. For instance, we try to understand how centrosome maturation proceeds, how bipolar spindles assemble and how chromosomes condense. In parallel, we also study regulatory mechanisms such as cell cycle checkpoints, in relation with DNA repair and sister chromatid cohesion. We are currently focusing on late mitotic events, post metaphase stages. The approaches we use to unravel these mitosis mysteries mainly focus on post-translational modifications of proteins. In particular, we invest a lot of energy to uncover the role of phosphorylation, and ubiquitination, in the regulation of mitosis. The group is also deeply engaged in cancer research. Indeed, defects in cell cycle controls are frequently associated with human cancers, and the proteins that regulate cell cycle appeared to be excellent targets for drug design. Not only do we search for inhibitors of cell cycle controls but also do we try to understand how misregulation of these control mechanisms participates to carcinogenesis.

 

Human Mitotic Chromosome visualised by epifluorescence microscopy. After spreading the chromosome is stained for DNA in blue and for two protein components: the cohesin, localised at centromeres, appears in green and the condensin, localised all along the chromosome axis, appears in red.  Human mitotic spindle visualised by epifluoresence microscopy. After fixation of mitotic cells, the spindle is stained for tubulin to visualise in green the microtubules that insure the dynamic architecture of the spindle, the DNA at the metaphase plate is stained in blue.  Abnormal human cell observed by epifluoresence microscopy. It shows several nuclei and centrosomes, often observed in cancer cells. The cell is fixed and stained for a- and b-tubulin to visualise microtubules in green and for g-tubulin to visualise the centrosomes in red. DNA appears in blue.

 

 

Subscribe to our newsletter