*4 Year MRC PhD Programme* mRNA processing in embryonic stem cell pluripotency and differentiation

Embryonic stem cells are pluripotent cells derived from early embryos that retain the ability to differentiate into all somatic cells. Pluripotency is dependent on the expression of key pluripotency regulators. On receiving signals to differentiate, gene expression profiles are reshaped to repress pluripotency factors and to express the proteins required of the new cell lineage. We investigate how cellular signalling pathways influence the gene expression machinery during differentiation and pluripotency to determine which proteins are expressed. Our focus is on understanding how cellular signalling pathways regulate the mRNA cap, a structure added to transcripts which is critical for gene expression. The mRNA cap recruits protein complexes which mediate processing and translation initiation. We have recently found that formation of the mRNA cap is regulated during neural differentiation which co-ordinately represses pluripotency genes and upregulates neural genes.

The PhD project would be to investigate how the mRNA cap is regulated during different differentiation programmes in human and mouse embryonic stem cells, and the impact that this has on gene expression and cell physiology. The student will be culturing and differentiating embryonic stem cells, performing genome editing, and analysing transcription and translation using next generation sequencing and mass spectrometry. The student will work within the laboratories of Victoria Cowling and Marios Stavridis, integrated in the Centre for Gene Expression and Division of Cell and Developmental Biology, at the University of Dundee. Dr Cowling provides expertise in gene expression analysis and Dr Stavridis provide expertise in Embryonic Stem Cell Biology.