Understanding the beginning of life: the biological role of UBE2Q1 and non-canonical ubiquitination in mouse embryonic cells

• 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.

Ubiquitination is a fundamental post-translational modification (PTM), which profoundly impacts diverse cellular functions, including protein degradation, localization, quality control, DNA repair, cell signalling, and immune response. 

Ubiquitin has been conventionally associated with lysine residues, however recent evidence challenges this view, revealing the attachment of ubiquitin to serine, threonine, and other biomolecules (non-canonical ubiquitination). Non-canonical ubiquitination is now emerging as fascinating and multifaceted PTM with the potential to interact and cross talk with other PTM (phosphorylation, glycosylation).

E2 conjugating enzymes (E2s) are central to the attachment of ubiquitin to its substrate. In recent breakthroughs, the De Cesare lab has identified a family of non-canonical E2s, namely UBE2Q1, UBE2Q2, and UBE2QL1, with the extraordinary ability to attach ubiquitin to serine, threonine, and other hydroxyl-containing biomolecules (non-canonical E2s). Importantly, removal of UBE2Q1 in mice has a profound impact and renders them infertile due to embryo implantation failure. These findings have shed light on the vital role played by non-canonical E2s in expanding the reach of ubiquitylation. 

This PhD research project focuses on understanding the role that these fascinating and poorly understood non-canonical E2s play within the cell. Our PhD candidate will harness cutting-edge technologies and methodologies, including mass spectrometry and molecular biology tools, to identify and characterize non-canonical E2s, their substrates and cellular functions. This is an exceptional opportunity to make ground-breaking discoveries and a substantial scientific contribution to the ubiquitin field.

Recently awarded the prestigious UKRI Future Leaders fellowship, the De Cesare Lab is part of the renowned MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU). Our laboratory benefits from state-of-the-art facilities and diverse technology platforms. These encompass molecular and cell biology, biochemistry and structural biology, empowering researchers to conduct experiments at the forefront of scientific discovery.

The successful PhD candidate will receive comprehensive training spanning mass spectrometry, high-throughput MALDI-TOF MS, biochemistry, cell and structural biology, and drug discovery. These acquired skills pave the way for exciting career opportunities in both academia and industry.   Beyond academia, the Life Sciences PhD Students' Association (PiCLS) offers a vibrant community with sports, social events, annual retreats, pub nights, and cultural festivities, enhancing the overall student experience.

If you are interested in becoming part of our non-canonical research endeavour, please get in touch ([email protected]) 

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.