Irreversible inactivation of ubiquitin and ubiquitin-like proteins

Host: Dario Alessi

Venue: MSI Small Lecture Theatre SLS

Abstract:

The post-translational modification of substrates with ubiquitin and ubiquitin-like proteins is one of the most prevalent and complex signalling events in eukaryotic cells. As a result, many diseases are caused by mutations or mis-regulation of the proteins involved in controlling these signalling pathways. Over the years, we have uncovered several unexpected findings on how these signals are regulated and mis-regulated in cells. One such finding was the discovery of an unusual viral protease that cleaves the C-terminus of ubiquitin and ubiquitin-like proteins. This activity ‘inactivates’ these modifiers since they can no longer be attached to substrates. In this seminar, I will discuss the discovery, characterisation, and utility of this protease for dissecting the complexity of the ubiquitin and ubiquitin-like systems. Lastly, I will discuss how I plan to use the Lister Award to study the consequence of this activity in cells and explore whether similar proteases exist in other disease-relevant areas of biology.

Bio:

Kirby obtained his PhD in Biochemistry from the University of Missouri, USA, under the guidance of Prof Jay Thelen. Here, his PhD research focused on applying state-of-the-art mass spectrometry techniques to study the phosphorylation networks of seed development in the model plant species Arabidopsis thaliana.

After completing his PhD, Kirby joined Prof David Komander’s lab at the MRC Laboratory of Molecular Biology in Cambridge, UK, to study the complexity of the ubiquitin system. Here, he developed innovative proteomic approaches to identify and understand the architecture of polyubiquitin chains, which provided critical insights into how these complex signals function in cells. In 2018, he joined Prof Brenda Schulman’s Department at the Max Planck Institute of Biochemistry in Munich, Germany, to pursue his interests in structural biology of multiprotein complexes. Since 2022, Kirby has been a Principal Investigator in the MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee. In 2023, he was awarded a Lister Prize Fellowship.

About the Seminar:

This is a Lister Institute of Preventative Medicine’s New Fellow Seminar and Award Presentation event. The Lister Institute Chair Prof John Iredale and Director Dr Sally Burtles will be in attendance to present the Lister Prize to Kirby and hear about his ongoing research. A celebration will be held after the seminar, and all are welcome!