MRC DTP 4 Year PhD Programme: mRNA cap regulation in embryonic stem cell function

This project is part of our exciting and challenging University of Dundee 4-year MRC DTP Programme in Quantitative and Interdisciplinary approaches to biomedical science. This PhD programme brings together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. Further information on the programme structure and training can be found at https://www.dundee.ac.uk/study/pg/phds/dtp/mrc-dtp/

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 the role of the mRNA capping enzymes in embryonic stem cell pluripotency and differentiation. Which genes do the capping enzymes control? What is the impact of the capping enzymes on embryonic stem cell differentiation? Should the capping enzymes be considered as therapeutic targets?

The student will be investigating T cell differentiation and function, 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. Prof Cowling provides expertise in gene regulation and Dr Stavridis provides expertise in embryonic stem cell biology.