Dr Janet Holt
The mammalian oocyte undergoes a unique pair of cell divisions in order to create a mature gamete capable of being fertilised. My research focuses particularly on the first meiotic division, and the molecular events controlling entry in the meiosis after the protracted Prophase I arrest. In particular I am interested in how the protein Cdh1/Fzr1 maintains the mature oocyte in an arrested state until the LH surge at ovulation. Cdh1/Fzr1 is an activator of the E3 Ubquitin E3 ligase, the APC, which is the master controllor of mitosis and meiosis - degrading cell cycle proteins at the appropriate time. Our laboratory discovered Cdh1/Fzr1 plays a unique role in Prophase I arrest of the oocytes by degrading Cyclin B1.
I also have a particular interest in the ageing egg and aneuploidy. We wish to understand why there is such a substantial rise in rates of aneuploidy with a female's age - a very relevant social issue considering the current trend toward having children later in life. We are using ageing mouse models to examine key proteins involved in the timing of Meiosis I and the fidelity mechanism controlling chromosome division (the Spindle Assembly Checkpoint).
Using microinjection of oocytes with fluorescently tagged constructs I study the dynamics of Meiosis I in real-time. Here, Cyclin B1-GFP localizes to the cytoplasm in the mature GV oocyte then translocates to the nucleus in the few minutes preceding Germinal Vesicle Breakdown.