Identify new suppressors of disease-causing proteasome mutations

• Funding – self-funded/externally sponsored applicants   (PhD Fees can be found here)
• Applications are accepted year round
• Standard Entry dates – January and September
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.

The proteasome degrades most cellular proteins in a controlled and timely manner and thereby controls many key processes. Proteasomes are also essential for maintaining intracellular protein quality control by removing misfolded, damaged, or aggregation-prone proteins. Thus, the proteasome is vital in all eukaryotes, with its dysfunction associated with various human diseases, including cancer and neurodegeneration. However, the impact of disease-causing mutations in proteasome genes on proteasome integrity and cell survival remains poorly understood. The use of the budding yeast Saccharomyces cerevisiae as a model system has been instrumental to understanding the physiological functions and mechanistic attributes of the proteasome. Using budding yeast, this project will aim to discover new suppressor genes rescuing disease-causing mutations of the proteasome. This will involve (1) generating CRISPR-Cas9 mutations in proteasome genes and monitor their impact on proteasome assembly and activity, (2) performing a genome-wide suppressor screen in proteasome mutants to identify new genes rescuing proteasome mutations, and (3) unravelling the underlying mechanisms behind the phenotypic suppression of proteasome mutations. Finally, suppressor genes having the strongest phenotypic rescue of proteasome mutations in yeast will be investigated in human cells.  

This PhD project will employ genome editing, biochemistry, molecular and cell biology and proteasome engineering to discover new suppressor genes rescuing proteasome mutations observed in diseases. This will pave the way for defining new strategies to restore protein homeostasis in disease. 

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.