3.5 Year MRC PhD Programme: Activating MINDY DUBs to kill cancer cells: A new strategy to kill cancer cells

Cancer cells are heavily reliant on their ubiquitin proteasome system (UPS) to maintain proteostasis and cell survival (1). This is because cancer genomes have many mutations in protein coding sequence, deletions, translocations as well as copy number variations (2). This results in the expression of mutant proteins and disruption of stoichiometric complexes, which have to be degraded. Thus, cancer cells are dependent on protein quality control systems for survival. Our lab recently discovered a new family of DUBs, that we named MINDY (3). These MINDY DUBs are evolutionarily conserved and are highly selective at cleaving K48-linked polyubiquitin, the signal that targets proteins for degradation. Our unpublished results show important roles for these DUBs in maintaining proteostasis in a cell. Importantly, overexpression of MINDY DUBs is toxic to cells. We therefore wondered if we could exploit these findings to impair proteostasis in cancer cells to kill them. Excitingly, we have uncovered a novel pathway that can activate MINDY DUBs in cells that results in cell death. However, the underlying mechanisms are still unclear. In this PhD project, a student with interest in signalling mechanisms and biochemistry will dissect how MINDY DUBs can be activated and apply this to cancer cell lines. After dissecting this pathway in detail and establishing the approach in cell lines, the student will also have the opportunity to prove their findings using mouse models. The student will be co-supervised by Prof. Victoria Cowling, at the Centre for Gene Regulation. We envisage establishing collaborations with pharmaceutical companies to translate this novel approach.


The University of Dundee is delighted to be recruiting for five PhD studentships, funded for 3.5 years, to start in September 2017. These projects bring together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK.

Eligibility: Applications for these MRC studentships are invited from excellent UK* students expected to hold (or be about to achieve) at least a 2:1 Honours degree in a relevant subject.
*Some EU students may be eligible for a full award if you meet Research Council residency criteria and other exceptions may apply.