Are you a PhD candidate intrigued by human embryonic development? Do you see the potential of embryo models and single-cell omics to uncover how embryos handle genetic abnormalities? Join our ZonMW-funded Genetic Plasticity consortium to explore the fate of aneuploid cells in early human development.
Aneuploidy, characterised by an abnormal number of chromosomes in a cell, is highly prevalent in human embryos derived through in vitro fertilization (IVF) and is a major cause of early pregnancy loss. On the other hand, persistent aneuploidies can lead to offspring with genetic syndromes such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 13), or Turner syndrome (XO genotype). To address these issues, pre-implantation genetic testing for aneuploidy (PGT-A) has been introduced into IVF clinical practice to exclude aneuploid embryos from transfer. However, there is growing evidence suggesting that pre-implantation embryos with mixed ploidy, known as mosaic embryos, can result in the birth of healthy babies, questioning PGT-A efficacy.
You will work on using novel stem cell-based embryo models as a proxy to study how human embryos cope with aneuploid cells. You will be expected to lead efforts in characterising cell fate biases of euploid/aneuploid human embryonic stem cells (hESCs) towards the main lineages as are present in the early human embryo, using hESC cell lines and embryo models (blastoids or related models). There will be a strong emphasis on the use of single-cell systems biology approaches, including high-resolution profiling of the transcriptome and open chromatin, and spatial transcriptomics. Assisted by our computational team, you will perform integrative computational analyses of the datasets you generate. Your discoveries will provide insight into how early human embryos develop and will help clinical embryologists make informed decisions when selecting embryos with varying aneuploid signatures for transfer to the uterus.
As part of your PhD training, you will take part in our medical biology educational programme for which you will assist in one or two courses per year and supervise BSc and MSc students within the context of your project.
Would you like to learn more about what it’s like to pursue a PhD at Radboud University? Visit the page about working as a PhD candidate.