Lab focus: ubiquitination in health and disease

Proteins, the machines that regulate all tasks within our cells, are constantly modified after they are made. These modifications can be highly tunable. 

We study such modifications to:

• Discover new principles and pathways they regulate 
• Develop new tools and techniques to study modifiers, and
• Harness the system and turn our insights into new medicines.

In the past five years we have focused on neurodegenerative disorders, including Parkinson’s disease, that affect the ageing population. We hope to uncover new diagnostics and treatments to stop or delay these incurable conditions. 

Research interest

We focus on the modifier ubiquitin, a small protein that modifies other proteins in a variety of distinct ways, known as the ‘ubiquitin code’.

Ubiquitination most commonly leads to destruction of the modified protein, but can also change its activation, interactions or localisation. Much of our work aims to enable studies of ubiquitin signals. 

A biological focus of the lab are deubiquitinases (DUBs) that remove ubiquitin from proteins. Using structural biology and biophysics, we have unraveled many mechanistic and regulatory principles of how DUBs cleave ubiquitin modifications.

Using preclinical models and in collaboration with human geneticists, we ascribe cellular and physiological function to select enzymes. Finally, in collaboration with industry, we are developing the first enzyme-specific DUB inhibitors, which may become new treatments for cancer and neurodegeneration.