Decoding the Bystander Effect in Protein Complex Degradation

• 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.

The “bystander effect” in protein ubiquitination — where both a target substrate and its binding partners are ubiquitinated by an E3 ligase — has been observed in several systems but remains poorly understood. This gap in understanding stems from a lack of effective chemical tools to dissect the molecular details of protein complex degradation.
This PhD project aims to uncover the molecular features that drive bystander ubiquitination within protein complexes. By developing and applying novel chemical tools, the project will advance our mechanistic understanding of E3 ligase–dependent protein degradation and guide the design of next-generation targeted degradation therapeutics.
You will combine small molecule synthesis, molecular biophysics, and structural biology to design chemical probes that both capture a protein complex and recruit it to E3 ligase machinery. These tools will be used to address key biophysical questions, including:
1) How do protein complex features—such as morphology, disorder, orientation, and stoichiometry—affect ubiquitination and degradation?
2) How does cooperativity between different E3 ligases (e.g., Cereblon and von Hippel–Lindau) influence polyubiquitination of a protein complex?
3) What chemical properties govern E3 ligase recruitment, and how can these be optimized?
4) Can cooperative binding drive selective ubiquitination of a specific protein within a multi-protein complex?
Training Environment:
The Cossar Lab, based within the Centre for Targeted Protein Degradation (CeTPD) at the University of Dundee, offers a multidisciplinary and collaborative environment equipped with world-class facilities. You will gain expertise in organic synthesis, molecular biophysics, and chemical and structural biology. The lab’s research integrates molecular glue, covalent, and fragment-based drug discovery approaches to tackle complex biological questions.
As a PhD candidate, you will collaborate closely with Professor Alessio Ciulli (second supervisor), a leader in targeted protein degradation. The project will focus on synthesizing heterobifunctional molecules and applying them to investigate the chemical and molecular biology of multicomponent protein complex degradation. You will receive tailored mentorship to build both technical excellence and professional development.
Candidate Profile:
We welcome motivated and ambitious candidates with a background in chemistry, biochemistry, or a related discipline. A strong interest in chemical biology and drug discovery is essential.
Why Dundee?
The University of Dundee hosts a vibrant, inclusive research community and is internationally recognized for excellence in life sciences. The CeTPD provides an outstanding environment for training the next generation of scientists in targeted protein degradation.

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.