The role of the kinetochore in meiotic aneuploidy
Year of award: 2021
Grantholders
Dr Gerard Pieper
University of Edinburgh, United Kingdom
Project summary
Meiosis is the process that generates our gametes: eggs and sperm. During meiosis, paternal and maternal chromosomes first duplicate and then segregate away in two consecutive divisions. The kinetochore is a vital molecular structure for this process because it assembles onto chromosomes and connects them to the spindle. In the first meiotic division, kinetochores from duplicated sister-chromatids uniquely face the same direction, allowing different parental chromosomes to segregate. In human eggs, the first meiosis is highly error-prone, often producing gametes with the wrong number of chromosomes. This worsens with advanced age, leading to miscarriages or diseases like Down syndrome, especially in older women. I aim to understand how kinetochores face the same direction, using frog egg extracts to build meiotic kinetochores in a test tube and identify their molecular components. Furthermore, I will use patient donations of human eggs from IVF clinics to determine how kinetochore defects contribute to infertility.