Mark Ashe was brought up in Cannock, Staffordshire where he attended Cardinal Griffin Comprehensive School. He obtained a first class honours degree in Biochemistry from Liverpool University and Professor Nick Proudfoot gave him the opportunity to perform his doctoral studies at Oxford University working on RNA processing.  Mark obtained his DPhil in 1995 and continued his work with Prof. Proudfoot as a post-doctoral research scientist until 1997.  Mark published four papers from his time in the Proudfoot lab, which enabled him to successfully apply for an EMBO long term fellowship to work with Professor Alan Sachs at the University of California, Berkeley.  

Here he worked on protein synthesis and RNA stability in yeast.  He also developed an interest in various stress responses and how these impact upon the post-transcriptional control of gene expression: an interest that remains to this day. In 2000, Mark moved to Manchester to take up a University Lectureship; he was promoted to Senior Lecturer in 2006 and Reader in 2011.

Mark's research group have been funded by The Wellcome Trust, the BBSRC and the Leverhulme Trust.  He has focussed on understanding mechanisms of post-transcriptional control and  this has led towards a more defined interest in the localisation and dynamics of mRNAs and translation initiation factors. More recently, Mark has applied his knowledge of gene expression and stress tolerance to synthetic biology approaches with a view to the production of biofuels and commodity chemicals in yeast. Mark has co-organised several national conferences and he serves on the editorial board of Molecular Biology of the Cell.

The regulation of translation and mRNA localisation

The Ashe lab focus on the mechanisms by which translation initiation and mRNA localisation are controlled and the signal transduction pathways which connect this process to cellular stress. In the past we have worked on novel mechanisms of translational control, including how glucose removal and the addition of fusel alcohols cause the rapid inhibition of translation initiation. Glucose starvation appears to taregt the eIF4A RNA helicase step whereas fusel alcohols inihibit the eIF2B guanine nucleotide exchange reaction. 

In a complementary approach the lab have assessed the intracellular localisation of translation initiation factors and mRNAs. A key controlled guanine nucleotide exchange step catalysed by eIF2B in the translation initiation pathway is localised to a very specific cytoplasmic focus that they has been termed the 'eIF2B body'. All of the five eIF2B subunits and all three subunits of the eIF2 G-protein for eIF2B localise to the same body (Figure 2).  In addition, similar bodies have been found in higher cells (Figure 3). This localisation could have important implications for both normal and regulated rates of translation initiation.

Severe translational stress (e.g. glucose starvation) also causes mRNAs and the translation initiation factors associated with them to relocalise to sites of mRNA degradation P-bodies and to alternative bodies which do not harbour mRNA decay enzmes.  These bodies have been termed EGP bodies after the principal components thus far found to reside in them i.e. eIF4E, eIF4G and Pab1p, or stress granules.

In more recent developments, we have expanded into utilising our knowledge of translational control in various projects including the production of biopharmaceuticals and biofuels, studies on the pathogenic yeast Candida albicans and the investigation of oocyte and early embryonic development in Drosophila.

Funding:

BBSRC.

Lab Members

Dr Jennifer Lui,  Gabriella Forte, Hassan Ahmed, Reem Swidah, Mariavittoria Pizzinga, Henry Oamen, Olugbenga Ogunlabi, Fabian Morales, Tawni Dornelles, Sarah Sheaik, 

Proteins are key molecules within cells, catalysing most of the biochemical reactions as well as serving numerous structural and regulatory roles. We are studying one of the fundamental questions in biology as to how proteins are made from the genetic messenger, mRNA, in a process termed translation and how this process is regulated. In particular, we are interested in the global down-regulation of translation that is observed under conditions of stress in yeast (e.g. alcohol stress and nutrient depletion). We study: the precise mechanism of control for a number of stresses: the fate of the mRNA under such conditions: and the fate of the translation factors. Our studies have expanded into many different areas, including the production of biopharmaceuticals and biofuels, the cellular organisation of mRNAs and translation factors into P-bodies and stress granules, and the role of translational control in the development of the Drosophila oocyte/embryo.