Upcoming Seminars

Viva Seminar - Mahdi Lamb

  • Venue: West Wing Lecture Theatre, Centre for Life
  • Start: Thu, 12 Mar 2020 13:30:00 GMT
  • End: Fri, 20 Mar 2020 14:15:00 GMT
Mahdi Lamb will be giving his pre-viva seminar, "Live-Cell Imaging of Human Oocytes and Regulation of Cohesin Removal in Meiosis II". The thesis covers cell cycle regulation (specifically in female mammalian meiosis) and fluorescence microscopy techniques (with a focus on live-cell time-lapse microscopy). 
The “maternal age effect” describes the striking increase in risk of miscarriage and chromosomally abnormal embryos and children from women older than 35. An increase in age, at least from mouse studies, shows the protein complex Cohesin is reduced with age. This protein complex ensures accurate segregation during both rounds of meiosis, by holding the chromosomes together and providing a counteracting force to spindle microtubules.
Despite a wealth of knowledge generated from human oocytes, there are few live-cell studies, in part due to the paucity of material. In this work, human oocytes specifically donated for research have been used to assess the effect of age on misalignment of chromosomes at metaphase I and -II, a predictor of missegregation. Using high-resolution live-cell microscopy, it is clear that increased age is associated with chromosomes that are misaligned in metaphase I and metaphase II.
At metaphase II, eggs arrest until they are fertilised by sperm. The regulation of how chromosomes separate at this point is poorly understood. While the bulk of Cohesin is removed in anaphase I, a small amount is “protected” and remains between the centromeres to allow for faithful segregation in meiosis II. Currently, there are only a few poorly described hypotheses explaining how the mechanisms that protect Cohesin in meiosis I are removed in meiosis II. One of these is the requirement of spindle tension to separate the protector from Cohesin in meiosis II. Here, I show that spindle tension is not required for deprotection and that alternative models should be considered, such as one which suggests that higher-order regulation around meiosis II is orchestrated by the Anaphase Promoting Complex and its coactivator Cdc20, APC/CCdc20, a protein complex that is active at anaphase onset.

 

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