How fungi manage stress: the role of RNA binding proteins in post-transcriptional adaptations to heat shock

Fungal pathogens are a major worldwide health burden, killing more people each year than malaria or tuberculosis. However, fungal pathogenesis and, in particular, how fungi adapt to human hosts at the start of infection, is poorly understood. On infecting their host, fungal pathogens are subject to stresses, such as heat shock, which they have to adapt to in order to grow and cause disease. We have recently characterized massive changes in RNA-protein interactions during heat shock, and are investigating how these changes allow cells to survive stress. We hypothesize that conserved RNA binding proteins (RBPs) are early responders in stress adaptation and that rapid change in post-transcriptional control of mRNAs by RBPs allows a rapid alteration of the proteome.

This project is a mixture of lab-based molecular biology and computational studies that will use quantitative, time-resolved methods to study changing populations of mRNA bound to RBPs. Using rapid cross-linking and cDNA analysis (CRAC) the student will generate RNAseq libraries that will give high resolution datasets (in time and sequence space) of changing RNA-protein interactions over the course of heat stress in budding yeast. These findings will give a mechanistic insight into stress adaptation that can be extended to pathogenic fungal models. There will be opportunities to integrate structural data on RNA-protein complexes, arising from studies in the Cook group. Finally, the data sets will be used to inform mathematical models of stress adaptation that can give systems level insights into mechanisms of fungal stress responses.

The successful candidate will be excited to combine experimental (yeast, RNA, proteins) with computational (bioinformatics, statistics, quantitative modeling) methods. You will have demonstrated basic skills in at least one of wet and dry work, and during the PhD will be trained to a high level in both. Both the Wallace and Cook groups will support your career development including laboratory, programming, presentation and writing skills. You will be encouraged to build a network of scientific colleagues in Edinburgh and more widely, including presenting your work at conferences.

This project will be jointly supervised by Edward Wallace (https://ewallace.github.io/) and Atlanta Cook (http://cook.bio.ed.ac.uk/). Interested candidates should enquire to us by email, describing your interest in this project in specific terms (see https://www.ed.ac.uk/informatics/postgraduate/apply/contacting-supervisors). The ideal email would say why you are interested in the subject matter (i.e. some combination of fungi, pathogens, stress adaptation, RNA, and sequencing methods), and also briefly describe your experimental and computational skills.