Nucleus centring and post-transcriptional regulation in mouse oocytes

Nucleus centring and post-transcriptional regulation in mouse oocytes

By In Aiv Internship On June 4, 2018

Internship title: Nucleus centring and post-transcriptional regulation in mouse oocytes

Name: Oocyte Mechanics and Morphogenesis
Affiliation: CIRB, Collège de France, CNRS UMR 7241 INSERM U1050
Address: 11 place Marcelin Berthelot, 75105 Paris

LAB Director
Name: Marie-Hélène Verlhac and Marie-Emilie Terret
Phone number: 0144271082

Name: Maria Almonacid
Phone number: 0144271638

Subject Keywords: Oocyte, meiosis, cytoplasmic flow, mRNA-Protein complexes
Tools and methodologies: Mammalian oocyte culture, microscopy, image analysis, modelling
Summary of lab’s interests: The goal of the lab is to understand how in Mammals, the female gamete, the oocyte, turns into a viable embryo, using morphological and biophysical approaches. Using the mouse oocyte model system, we study the impact of actin meshes in the control of chromosome positioning and on the developmental potential of the oocyte. Current projects in the lab focus on two aspects of the oocyte biology, namely nucleus position and cortical properties, that constitute non-invasive predictors of viability of early embryo development that could be used easily in Assisted Reproduction Technologies.

Project summary: In mouse oocytes, nucleus central position, which is crucial for the success of meiotic divisions, is achieved by a Formin 2 (Fmn2)-nucleated actin cytoplasmic mesh. Post-transcriptional regulation through mRNA translation or degradation is essential in the oocyte since meiotic divisions and the first steps of embryonic development take place without transcription. The internship is part of the global project of understanding the role of nucleus centring in post-transcriptional regulation of gene expression. mRNAs not engaged in polysomes are stored in RNPs granules (mRNA-Protein complexes), waiting for translation at key stages of meiosis. Live labeling of RNPs showed that their size and dynamics are driven by a continuous streaming generated by the cytoplasmic actin mesh. To find a functional link between cytoplasmic streaming and post-transcriptional regulation, we identified in silico RNA binding motifs enriched in the 5’ and 3’ UTR of about 2000 Fmn2 -/- deregulated genes. These motifs correspond to 59 RBPs (RNA Binding Proteins). We will use these RBPs as new tools for live imaging of RNPs. We will also perturb the cytoplasmic streaming by playing with Myosin Vb activity. Together, this will contribute to establish a physical model for the behavior of RNP granules experiencing the cytoplasmic stream.

Interdisciplinary aspect of the project: The student will benefit from the lab expertise in mouse oocyte biology. For the experimental part, he/she will be introduced to mouse oocyte micromanipulation techniques. The student will be proactive in developing tools to analyze RNPs dynamics. For that, he/she will be assisted by the CIRB imaging facility if necessary. The student will be encouraged to propose ideas for elaborating a physical model for RNPs behavior, in collaboration with theoricians at UPMC (Raphaël Voituriez). Although it does not correspond to the main part of the internship, elements of bioinformatics could be useful to browse into datasets from transcriptomic analysis.