MSc by Research: Designing Molecular Glue Stabilizers to Restore Tumour Suppressor Function

About the Project

Molecular glues, small molecules that facilitate the assembly of biomolecular complexes, have emerged as a transformative drug discovery strategy for treating diseases such as cancer and neurodegeneration. Their gain-of-function mechanism has demonstrated remarkable therapeutic potential. Among these, molecular glue degraders are the most well-characterized approach, highlighting the significant promise of this drug technology.

However, this represents only the tip of the iceberg for this drug discovery technology.

Cancer cells often employ strategies to destabilize critical regulatory proteins, such as the tumour suppressor p53. This destabilization frequently arises from point mutations that lead to protein degradation, allowing cancer cells to bypass essential regulatory checkpoints. Stabilizing these mutated proteins by capturing them within biomolecular complexes offers a compelling opportunity to restore tumour-suppressor function.

In this master’s research project, you will explore a molecular glue stabilizer approach to enhance p53, and it’s isoforms, with it’s interact endogenous partner proteins.

In this research project you will.

1. Screen and identify the hit molecules that bind to the tumour suppressor complex.
2. Biophysically and structurally characterize tumour suppressor complex stability.
3. Develop a structural-activity relationship to investigate cooperative multi-component complex assembly
4. Study how molecular glue stabilization influence protein stability in vitro.

The Cossar Lab, based within the Centre for Targeted Protein Degradation at the University of Dundee, provides a multidisciplinary environment with world-class facilities. Here you will be exposed to both academic and industry scientist across the breadth of Medicinal Chemistry to Cellular Biology. This includes exposure to researchers from leading biotechnology companies such as Boehringer-Ingelheim, Eisai, and Tocris.

This project will equip you with expertise in organic synthesis, biophysical assay screening, protein production, and small-molecule design. Through a combination of hands-on research and collaborative opportunities, you will develop an in-depth understanding of molecular biophysics, chemical biology, and drug discovery. Training will also focus on professional development, including presenting your scientific work, collaborating within multidisciplinary teams, networking, and scientific writing.

The Cossar lab research uses molecular glue-, covalent-, and fragment-based drug discovery approaches to address intricate biological questions, giving you a comprehensive training experience.

The successful candidate will have foundational knowledge in drug discovery, synthetic chemistry, or chemical biology. While the project focus areas can be tailored to your interests, you will receive dedicated support in honing technical skills and professional competencies.

The University of Dundee’s inclusive research community is an ideal setting for ambitious individuals. We welcome applications from all talented candidates, particularly those with the drive and potential to make a significant impact in the field of drug discovery.

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.