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


   School of Biological Sciences

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  Dr A Cook  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Interested individuals must follow Steps 1, 2 and 3 at this link on how to apply
http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

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 enthusiastic about combining experimental (yeast genetics, RNA and protein biochemistry) with computational (bioinformatics, statistics, quantitative modeling) methods.

Further Information
This project will be joint supervised by Atlanta Cook and Edward Wallace
http://www.wcb.ed.ac.uk/research/cook
http://cook.bio.ed.ac.uk/

https://scholar.google.co.uk/citations?user=7FLIJBAAAAAJ&hl=en

Funding Notes

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

If you would like us to consider you for one of our scholarships you must apply by 12 noon on Monday 5th January 2018 at the latest.

References

Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress. Wallace, et al., Cell 2015. doi:10.1016/j.cell.2015.08.041

Stress Adaptation. Brown, et al., Microbiol Spectr 2017. doi:10.1128/microbiolspec.FUNK-0048-2016
Protein-RNA interactions: new genomic technologies and perspectives.

König, et al., Nat Rev Genet 2012. doi:10.1038/nrg3141

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