University of Dundee

MRC DTP 4 Year PhD Programme: Investigating mRNA cap regulation in pluripotency and differentiation

This project is offered as part of the University of Dundee 4-year MRC DTP Programme “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.  The outstanding biomedical research at the University of Dundee was recognised by its very high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK.  A wide range of projects are available within this programme crossing exceptional strengths in four key areas: Infection and Disease; Responses to Cellular Stresses; Development, Stem Cells and Neurobiology; and Big Data and Translation.  All students on this programme will receive training in computational biology, mathematical biology and statistics to equip with the quantitative skills in tackling complex biological questions.  In the 1st year, students will carry out 3 rotation projects prior to selection of the final PhD project.

We are interested in how cells co-ordinate the expression of hundreds or thousands of genes. In particular we are interested in the gene expression changes which drive new cell functions when cells receive external signals, e.g. when a T cell encounters an antigen orwhen an embryonic stem cell receives a developmental signal. Our focus is on the role of the mRNA capin co-ordinating gene expression. The capprotects RNA during transcription and recruits the factors that mediate RNA processing and translation. The project will involve investigating the impact of the mRNA capping enzymes on transcription, RNA processing and translation in embryonic stem cells and/orT cells. The student will use the latest next generation sequencing technologies to map gene expression profiles and use advanced computational methodologies to analyse the data.Training for all aspects of the project is available in the lab and on university and external courses. 

Victoria Cowling is a group leader in the Centre for Gene Regulation and Expression.  Her group investigates how regulation of the mRNA cap influences cell function and fate.  The project will be supported by postdoctoral researchers working in cell biology, biochemistry, bioinformatics and physiology.

Tom Owen Hughes is also a group leader in the Centre for Gene Regulation and Expression, with expertise in the analysis of gene expression, including biochemistry and bioinformatics.

Recent work from the lab can be found in the following references: Grasso L, SuskaO, Davidson L, Gonatopoulos-Pournatzis T, Williamson R, Wasmus L, WiedlichS, PeggieM, StavridisMP and Cowling VH (2016) 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 PMID 27452456

Varshney D, Lombardi O, Schweikert G, Dunn S, Suska O and Cowling VH(2018) mRNA cap methyltransferase (RNMT-RAM) is required for RNA pol II-dependent transcription Cell Rep. 2018 May 1;23(5):1530-1542. doi:10.1016/j.celrep.2018.04.004 PMID: 29719263

Aregger M, KaskarA, Fernandez-Sanchez ME, Simone Weidlich S andCowling VH (2016)CDK1-cyclinB activates RNMT co-ordinating mRNA cap methylation with G1 phase transcription Molecular Cell2016 Mar 3;61(5):734-46. doi: 10.1016/j.molcel.2016.02.008 PMID: 26942677