Molecular Adaptation: Probing how Candida glabrata evolved to be a human pathogen.

Background and significance of research

In this exciting, post-genomic era biologists are obtaining significant insights into the molecular
composition of life. Using comparative genomics we are for the first time, able to identify sequence
differences between species that allow us to make hypothesis as to the molecular basis of their
differences. This provides us with insights into how evolution and adaptation works at the molecular
level.
We are interested in applying these techniques to understand how the yeast species, Candida
glabrata adapted to surviving within a human host. Furthermore, C. glabrata accounts for
approximately 20-25% of cases of candidiasis in the UK, a human infectious disease, and therefore
insights gained into the adaptation of C. glabrata, have potential therapeutic value through the
identification of novel anti-fungal targets.
Using comparative phylogenetic approaches we have previously identified 19 C. glabrata genes that
are predicted to be involved in its adaptation. Each gene functions to maintain chromatin integrity
within C. glabrata. The goal of this PhD is to seek experimental evidence to validate our
computational predictions, by asking whether these 19 chromatin genes contribute to the known
adaptive phenotypes of C. glabrata.

Research aims

1. Using the CRISPR-Cas9 system to edit the genome of C. glabrata and remove each of the
19 chromatin-related genes.
2. To assay the effects of removing each of the 19 chromatin-related genes on C. glabrata
fitness under adaptive conditions, using a fluorescence based growth assay.
3. To monitor gene expression and chromatin integrity in each strain lacking one of the 19
genes, using RNA-seq and ChIP-seq respectively.

For an application form and full details on how to apply, please visit https://dap.qub.ac.uk/portal/user/u_login.php . Applicants should also upload a CV and a project proposal.