; University of Manchester
Mark Ashe was brought up in Cannock, Staffordshire he went to Liverpool University where he obtained a first class honours degree in Biochemistry. Professor Nick Proudfoot at the Sir William Dunn School of Pathology in Oxford gave him the opportunity to undertake a DPhil 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, Reader in 2011 and Professor in 2016. 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. Most of this work uses yeast as a model organism, but some has either been extended into mammalian cells or applied to industrial projects.
Across many biological systems, mRNA localisation and translation form part of a strategy allowing for polarised protein production. However, our recent research shows that mRNAs encoding proteins that are not necessarily thought of as polarised are also translated at discrete sites within the cell. We and others have termed these sites 'translation factories', since functionally related mRNAs are colocalised and translated at such sites. For instance, using a range of live cell and fixed cell imaging techniques, we have demonstrated that glycolytic and translation factor mRNAs are actively translated in discrete factories. In past work, we have investigated possible functions for this localised translation of specific functional classes of mRNA including improved translation efficiency, co-ordinated posttranscriptional regulation and orchestrated inheritance of mRNA. In this talk I will cover our recent work where this co-ordinated mRNA localisation and translation could have implications for the formation of protein complexes. Formation of protein complexes within translation factories would overcome issues surrounding proteins locating one another within a sea of macromolecules and potential nonproductive interactions. Co-translational mRNA interactions within granules could therefore favour native assembly of protein complexes. Understanding the requirements for the formation of translation factories and the extent of co-translational complex production within them could provide vital information regarding protein complex activity and the influences of inappropriate formation of protein aggregates.
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