University of Dundee

A strategy to kill cancer cells by inducing proteotoxic stress

Cancer cells are heavily reliant on their ubiquitin proteasome system (UPS) to maintain proteostasis and cell survival. This is because cancer genomes have many mutations in protein coding sequence, deletions, translocations as well as copy number variations. This results in the expression of mutant proteins and disruption of stoichiometric complexes, which have to be degraded. Moreover, malignant cells have high rates of proliferation and protein synthesis. Thus, cancer cells are dependent on protein quality control systems for survival. The available projects build on the Kulathu lab’s main interests in understanding how protein degradation and proteostasis are modulated by the ubiquitin system.

The overall aims of the projects in this area will be to get a detailed understanding of how ubiquitylation regulates the stability and degradation of oncogenic proteins and how strategies can be designed to modulate them. Specifically, we are interested in exploring a newly identified pathway in the lab that disrupts protein degradation, thus inducing proteotoxic stress. In this project, you will determine how this pathway works and develop strategies to modulate this pathway in cancer cells. During this project, you will have opportunities to learn and apply a wide range of cell biological methods including CRISPR/Cas9 genome engineering, proximity-labelling based identification of interacting proteins, proteomics, high-resolution microscopy, live cell imaging and access to mouse models.

At the MRC PPU, as well as the possibility of a PhD in one particular lab, we offer the possibility of two 4.5-month rotations in labs of their choice. A range of other projects from MRC PPU scientists are advertised on this website. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group.

To apply, please send a CV with contact details of three referees to and a cover letter explaining why you have chosen to apply to MRC PPU to mrcppu-phd-admin@dundee.ac..uk. The closing date for this round of applications is March 31st, with interviews in April.

Eligibility