PhD-Exploring Non-Canonical Ubiquitination and Its Biological Roles
PhD @University of Dundee posted 2 days agoJob Description
- 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) crucial for a wide range of cellular processes, including protein degradation, localization, quality control, DNA repair, cell signaling, and immune responses. Traditionally, ubiquitin attaches to lysine residues via isopeptide bonds. However, recent advances have uncovered a novel form of ubiquitination – non-canonical ubiquitination – where ubiquitin binds to serine, threonine, and other hydroxyl-containing biomolecules through ester bonds. This dynamic and less stable modification challenges established paradigms and opens up new possibilities for interactions with other PTMs, such as phosphorylation and glycosylation. Investigating non-canonical ubiquitination promises to deepen our understanding of cellular mechanisms and identify new therapeutic targets for diseases linked to dysfunctional ubiquitination.
The De Cesare Lab has identified several non-canonical ubiquitin conjugating enzymes (E2s) – UBE2Q1, UBE2Q2, and UBE2QL1 – that mediate ubiquitin attachment to non-lysine residues. Notably, UBE2Q1 knockout mice exhibit infertility due to defective embryo implantation, highlighting the critical role of these non-canonical E2s in early developmental processes and reproductive biology. Additionally, altered expression of UBE2Qs has been observed in various human cancers, raising important questions about their roles in human health and disease.
Research Questions
This PhD project will address the following key questions:
- Roles of Non-Canonical Ubiquitination: How does non-canonical ubiquitination affect cellular processes and human health, including links to infertility and cancer?
- Biological Functions of Non-Canonical E2s: What are the substrates and functional roles of non-canonical E2s (UBE2Q1, UBE2Q2, UBE2QL1) in different cellular contexts?
- Interactions with Other PTMs: How does non-canonical ubiquitination interact with and regulate other PTMs such as phosphorylation and glycosylation?
Methodology and Training Opportunities
This project offers flexibility to align with the student’s specific interests and incorporates a range of advanced methodologies:
- Mass Spectrometry: Use MALDI-TOF and LC/MS to identify and analyze substrates of non-canonical E2s, providing detailed insights into their interactions and modifications.
- Protein Biochemistry: Employ cutting-edge techniques to study protein interactions, modifications, and functional properties of non-canonical E2s and their substrates.
- Structural Biology: Utilize X-ray crystallography and cryo-electron microscopy to reveal the structural details of non-canonical E2-substrate interactions.
- Molecular Biology: Perform gene editing, expression analysis, and functional assays to elucidate the roles of non-canonical E2s and their substrates.
- Cell Biology: Conduct cellular assays to evaluate the impact of non-canonical ubiquitination on cellular functions and disease models.
This comprehensive training will provide the student with valuable skills across multiple disciplines, preparing them for successful careers in both academic and industrial settings.
Application
To apply or for more information about this PhD position, please contact Dr. Virginia De Cesare at vdecesare@dundee.ac.uk. Join us to explore the innovative field of non-canonical ubiquitination and contribute to pioneering research.
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.
How to apply
Please contact the principal project supervisor to discuss your interest further, see supervisor details below.
For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk
