Regulation of mRNA capping by pluripotency signalling pathways in embryonic stem cells.

Supervisors: Victoria Cowling, Greg Findlay

Project Description
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.  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 student will investigate how cellular signalling pathways influence the mRNA capping enzymes during differentiation and pluripotency. 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 of embryonic stem cells which co-ordinately represses pluripotency genes and upregulates neural genes. 

The PhD project would be to investigate how the mRNA cap is regulated by signalling pathways 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 Prof Cowling in the Centre for Gene Expression and Dr Findlay in the MRC Protein Phosphorylation Unit at the University of Dundee.

References:

  1. mRNA Cap Methylation in Pluripotency and Differentiation Cell Rep. 2016 Aug 2;16(5):1352-65. doi: 10.1016/j.celrep.2016.06.089. Epub 2016 Jul 21.
  2. Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity. Cell Rep. 2016 Aug 16;16(7):1820-8. doi: 10.1016/j.celrep.2016.07.033. Epub 2016 Aug 4.
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