Deciphering the role of UBE2Q1 and non-canonical ubiquitylation in tumorigenesis

• Funding – TENOVUS funded 3-year studentship, providing tuition fees, training/research costs and an annual tax free stipend of £21, 403
• Start Date – 14th September 2026
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a subject relating to biomedical sciences

Ubiquitylation is a central Post-Translational Modification (PTM) that regulates protein stability, signalling, and many core aspects of cell biology. Classically, ubiquitin is attached to lysine residues on target proteins via isopeptide bonds. However, it is now clear that this view is incomplete. Ubiquitin can also be linked to alternative amino acids, including serine and threonine (via ester bond), and in some contexts to non-protein substrates such as carbohydrates and nucleic acids.

This expanded, “non-canonical” ubiquitylation challenges the traditional framework of ubiquitin biology and points to a much greater chemical and functional diversity than previously appreciated. It suggests that cells have additional, largely unexplored mechanisms to control protein function and signalling dynamics. Understanding these pathways offers new opportunities to uncover how cellular pathway operate under normal conditions and how their disruption contributes to disease.

This PhD project will investigate how non-canonical ubiquitylation contributes to cancer. It focuses on the ubiquitin-conjugating enzyme UBE2Q1, a recently identified mediator of non-canonical ubiquitylation that is often upregulated in aggressive tumours and associated with poor clinical outcomes. By defining the cellular targets and functions of UBE2Q1-driven ubiquitylation, the project aims to uncover previously unrecognised disease mechanisms and identify new opportunities for biomarker development and targeted therapies.

The project will address the following key questions:

• Which proteins are targeted by UBE2Q1, and which residues are modified?
• How does non-canonical ubiquitylation influence protein function and cellular behaviour?
• Can this pathway be leveraged for cancer diagnosis, prognosis, or therapeutic intervention?

To address these questions, the student will combine molecular biology, protein biochemistry, and omics approaches, including proteomics and genomics. You will reconstitute enzymatic reactions in vitro, map ubiquitylation sites using high-resolution LC-MS/MS, and investigate the functional consequences of non-canonical ubiquitylation in cancer cell lines using genome editing and cell biology assays. Integration with large-scale cancer datasets will further link molecular discoveries to clinical relevance.

You will be based at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), University of Dundee, a world-leading centre for signal transduction research. The environment is highly collaborative and interdisciplinary, offering access to cutting-edge facilities and expertise. The project is further strengthened by active collaborations with leading research institutes, including the Cancer Research UK Scotland Institute in Glasgow.

The student will also benefit from training through the University of Dundee Doctoral Academy, developing both scientific and transferable skills.

Overall, this PhD provides a unique opportunity to contribute to a rapidly emerging field, uncover new principles of cellular regulation, and generate insights that could ultimately transform our understanding and treatment of cancer.

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.