University of Dundee

Ubiquitin E3 ligases: function, structure and therapy

All proteins become posttranslationally modified during their lifetime and this orchestrates a large part of cellular biology. Nature’s gamut of posttranslational modifications (PTMs) is vast and the list continues to grow. A PTM which is known to regulate essentially every aspect of cell biology, in both health and disease, is ubiquitylation. Ubiquitylation involves the covalent attachment of the small protein ubiquitin to substrate proteins. This earmarks the proteins for degradation or modulates some other aspect of their function. This process lies at the heart of many diseases, hence there is huge therapeutic potential for the treatment of a broad range of diseases including cancer, neurodegeneration and autoimmune disorders. The Virdee lab study the remarkable enzymatic machinery that is tasked with transferring ubiquitin to specific substrates. These enzymes are known as E3 ligases and our lab develops novel technologies that coax them into divulging important insights into their mechanism and cellular function.  The lab is highly interdisciplinary as we use an array of techniques such as X-ray crystallography, proteomics and even organic chemistry. Inquisitive and technically minded applicants should find the lab a stimulating environment to conduct research. This ranges from establishing the cellular function of poorly characterized E3 ligases, discovery of entirely novel family members, or the development of state-of-the-art technology.

References

Pao et al., Nature Chemical Biology 2016, 12 (5), 324.

Pao et al., Nature 2018, 556 (7701), 381.

 

Eligibility