PhD Training Programme for Clinicians at the University of Cambridge. (360G-Wellcome-087005_Z_08_Z)

There is a high incidence of mosaic aneuploidy in human pre-implantation embryos, however the chance of an affected fetus is very low. We wish to explore the hypothesis that in an embryo which is a mosaic of normal and aneuploid cells, the clone of aneuploid cells might be more likely to contribute to the trophectoderm, an extra-embryonic lineage which gives rise to placenta rather than the embryo itself. First we aim to generate chimeric embryos in which normal and abnormal cells are in contact and follow the fate of both types of cells and their contribution to specific lineages; pluripotent epiblast that give rise to the embryo versus trophectoderm that give rise to placenta by time-lapse microscopy. Second, we will generate normal and aneuploid cells within a single embryo by interfering with the spindle assembly checkpoint proteins, the natural safeguard against aneuploidy and examine the fate of both cell types and mechanisms by which they reach their specific positions within the embryo and thus fate. Finally, we aim to develop and use an in-vivo chromosome marker that will allow us to directly monitor the generation of aneuploid cells in the above experiments.