RNA Stability in Placental Development 

Early mammalian development is underpinned by a series of cell state transitions as multiple lineages form with distinct transcriptional programmes. There is accumulating evidence that post-transcriptional regulatory mechanisms play a key role in these developmental transitions. Currently this is an understudied facet of developmental biology and in particular placental development. Several publications have reported embryonic lethality with an embryonic or placental phenotype in mice where an RNA binding protein or decay factor has been knocked out. However, detailed phenotyping and in-depth molecular analysis is lacking in most of these examples.

The aim of this PhD project is to use embryonic and trophoblast stem cell lines, as well as in vivo models, to understand changes in RNA stability during normal differentiation events and understand the consequences of disruption of RNA processing or decay pathways. In this way we will be able to elucidate the molecular mechanisms underlying lineage formation defects and embryonic lethality in this context.

Methods: cell culture, RNA-sequencing, transcriptomic analysis, CRISPR gene editing, western blotting, histology, immunofluorescence