Our laboratory uses a combination of mouse genetics and cell biology to answer questions pertinent to improving women’s reproductive helath and furthering our basic understanding of how meiosis is regulated at the molecular level. When an egg makes a chromosome segregation mistake this event can negatively impact an organism’s fertility or result in a developmental disorder like Down Syndrome. The Aurora kinases (AURKs) are highly conserved throughout evolution, and comprise a family of proteins that are well known for their roles in maintaining proper chromosome numbers during the mitotic cell cycle. Mammals contain 3 AURK isoforms: AURKA, AURKB and AURKC. AURKA and AURKB are expressed in nearly all cell types. AURKC is most similar in sequence to AURKB but its expression is largely limited to sperm and egg. Oocytes contain both AURKB and AURKC, but we still know little about the meiotic functions of these critical chromosome segregation regulators.
The student's project will entail determining how AURKB/C are differentially regulated during oocyte meiosis by perturbing the function of an upstream regulatory kinase called Haspin. The student will manipulate mouse oocytes in cell culture in the presence of a chemical inhibitor of Haspin. They will use microscopy to isolate, manipulate and analyze the oocytes. Some of the analysis will include determining chromosome number in the egg after meiosis I, assessing spindle and chromosome morphology and determining cell cycle stages. This project will contribute to the field of understanding how chromosome segregation is regulated during meiosis and why, in females, it is highly prone to errors.
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