Dr David Komander
Specificity in the Ubiquitin System
David Komander studied in Germany and Scotland, and worked on protein kinase structures during his PhD in Dundee. As a postdoc in London, he initiated work on tumour suppressor deubiquitinases, leading to the first structures of CYLD and A20. In 2008, he started his lab at the MRC Laboratory of Molecular Biology in Cambridge, where he has since worked on E3 ligases, ubiquitin binding domains and deubiquitinases, that make, bind and break unstudied ubiquitin chains. David is a Lister Fellow and EMBO member.
The Komander lab tackles the complexity in the ubiquitin system by focussing on the different forms of the modification. Identifying proteins and enzymes that provide specificity for e.g. distinct ubiquitin chain types, enabled a detailed molecular understanding and insights into mechanisms of linkage-specificity, and has led to the discovery of new enzymes, such as the Met1-linkage specific deubiquitinase OTULIN. Functional characterisation of OTULIN recently provided new insights into the biology of Met1-linked ubiquitin chains. A current focus of the lab are ubiquitination events on mitochondria and in mitophagy, where a defined set of proteins establishes an exciting set of ubiquitin signals, including phospho-ubiquitin and unstudied Lys6-linked polyubiquitin chains. In this and other settings, pharmacological targets in the ubiquitin system are emerging, and the first translational projects are now coming to fruition.