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> Stages de M2 > Liste des stages proposés pour l’année 2016-2017 > Cell Cycle Regulation of the Meiosis I to Meiosis II Transition in (...)

Cell Cycle Regulation of the Meiosis I to Meiosis II Transition in Mammalian Oocytes

proposé par Katja WASSMANN, Biologie du Développement, UMR7622 CNRS

Projet de stage :

We study cell cycle regulation and spindle assembly checkpoint (SAC) control between meiosis I and II. Furthermore we are interested in understanding how Cohesin, which is holding sister chromatids together, is removed in meiosis I and II. This M2 project will focus on the transition from meiosis I to meiosis II. The candidate will address how the cell cycle is controlled during this transition. We want to elucidate how Separase, the protease required for cleavage of Cohesin, is maintained inactive as oocytes enter meiosis II, and again activated at anaphase onset in meiosis II. We have a combination of conditional knock-out mouse models and specific inhibitors at our disposition to dissect the molecular mechanisms of cell cycle progression and Separase inhibition. More specifically we are interested in the role of B-type cyclins at this stage. We have recently developed a biosensor to follow Separase activity by confocal live imaging during progression through the meiotic divisions, and this sensor may now be used to determine how cyclin-dependent kinases control Separase in mouse oocytes. In addition, accessibility of Cohesin for Separase cleavage in meiosis I and II will be determined.

Techniques mises en œuvre par le stagiaire : We want to understand why oocytes missegregate chromosomes at such high rates, using mainly state-of-art imaging approaches, chemical genetics, and conditional knock-out mouse models. Proteins required for Cohesin removal will be analysed by immunofluorescence staining on chromosome spreads. Progression through meiosis I and II will be studied by live imaging of oocytes that have been microinjected with mRNAs coding for proteins of our choice. The candidate will be able to use sophisticated techniques that have been set up in the lab and that are available to adress questions related to human infertility.

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