Identifying novel chromosome segregation regulators in human oocytes and embryos

Host: Tony Ly & Tomo Tanaka

Venue Sir Kenneth & Lady Noreen Murray Seminar Room , CTIR 2.84

Abstract

Human embryos have a high rate of chromosomal abnormalities (aneuploidy). Aneuploidy is generated both at the level of the oocyte during meiosis and during the first few mitotic embryonic divisions, all of these are highly error-prone. I will present two projects investigating new players and mechanisms in mediating accurate chromosome segregation in oocytes and embryos.

Firstly, focussing on meiosis, it is known that the kinetochores, large protein complexes that tether chromosomes to spindle fibres, are often deficient in human oocytes. How kinetochores are adapted for the two specific meiotic chromosome segregation events in vertebrates is largely unknown. To solve this, I have set up methods to study the proteomic composition of meiotic kinetochores through in vitro reconstitution in frog oocyte extracts. With this method I have discovered novel kinetochore proteins that also function to mediate correct chromosome segregation in human oocytes. Next, I have focussed on deciphering the origin of multinucleation in 2-cell human embryos, a feature that is of unknown origin but is potentially correlated to low embryo quality. Through live imaging of the first human embryonic mitosis we discovered that multinucleation is a consequence of loss of spindle and metaphase coherence. This highlights unique features of human embryonic mitosis that could be key to understanding their error-prone nature.

Bio

Gerard did his PhD in the lab of Snezhka Oliferenko at the Francis Crick Institute and King’s college London. Here he worked on chromatin-nuclear envelope attachments and nuclear envelope dynamics in the non-standard fission yeast S. japonicus. He then moved to the lab of Adele Marston at the University of Edinburgh where he obtained a Sir Henry Wellcome Fellowship to study the role of kinetochores in meiosis in frog and human oocytes.

https://www.biorxiv.org/content/10.1101/2025.08.20.671312v1

https://www.biorxiv.org/content/10.1101/2023.01.13.523952v1