Regulation of the expression dynamics of the ergosterol pathway in Saccharomyces and Candida yeasts.

This PhD project aims to dissect at the post-transcriptional level the pathway by which ergosterol and aromatic amino acids are synthesized in fungi. As well as being a critical plasma membrane component, ergosterol is used to generate a range of steroid pharmaceuticals and the synthesis pathway is targeted by various medically important anti-fungal compounds. Aromatic amino acids are also produced by pathways that are not present in animal cells. Preliminary work on these pathways in our labs suggests that the mRNAs encoding the components of the pathways are localised to discrete foci in bakers yeast. This localisation is highly reminiscent of our recent discoveries of translation factories in yeast. These represent cytoplasmic sites where functionally related mRNAs are translated allowing regulation of the levels, location and interactions of the encoded proteins. In this project, we will use a range of microscopic techniques in both live and fixed cells to study the localisation and translation of all of the pathway mRNAs. We will dissect mechanisms by which these mRNAs are localised and address what the purpose of the localisation is. We will investigate the localisation in both Saccharomyces and Candida yeast species, and we will challenge these yeasts with different stresses and antifungal agents to ascertain the impact on mRNA localisation and ergosterol/ aromatic amino acid synthesis.