Lister New Fellow Seminar

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. One process that is heavily reliant on these signals is the cell’s defence response against viral infection. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein, which is highly upregulated upon viral infection and interferon stimulation, resulting in the attachment of ISG15 to a vast array of substrates. In turn, many viruses have evolved sophisticated mechanisms to disarm this host defence system. However, a lack of available tools to study ISG15 and mechanistic information on how these signals result in specific cellular outcomes has obstructed our understanding of this ubiquitin-like protein. In my seminar, I will present our recent progress in this area and discuss key outstanding questions and future directions. Finally, I will discuss how the Lister Award is enabling us to extend upon these discoveries to further our understanding of this critical and enigmatic post-translational modification of the immune system.

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 Sir 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!