Nonsense Mediated Decay in Placental Development

Supervised by: Dr Claire Senner (ces207@cam.ac.uk) and Dr Erica Watson (edw23@cam.ac.uk)

Project Title: Nonsense Mediated Decay in Placental Development

Project description 

Placental development is crucial in the establishment of a healthy pregnancy with poor placentation underlying many pregnancy complications. The molecular mechanisms underpinning the earliest stages of placental development are not well understood, but central to understanding how complications arise. Post-transcriptional regulatory mechanisms are an understudied facet of developmental and reproductive biology but there are several examples of single gene mutations in mouse that disrupt an RNA decay pathway or delete an RNA binding protein that result in placental phenotypes. A clear and comprehensive understanding of the pathways and mechanisms involved and how they shape the transcriptomic landscape is lacking. Preliminary data in the Senner lab show that disruption of the Nonsense Mediated Decay (NMD) pathway results in a severe placental phenotype arising shortly after implantation with defects in the trophoblast stem cell compartment and accompanied by embryonic lethality. The aim of this PhD project is to explore how NMD contributes to placental development and how the trophoblast defect in turn contributes to embryonic lethality. The project will involve the use of cell culture, genetic mouse models, and embryo manipulation, combined with in-depth transcriptomic analysis to address how NMD as a post-transcriptional regulatory mechanism plays a key role in trophoblast stem cell regulation and placental development