We will offer some thoughts about the ubiquitin code as an emergent property of our understanding of the ubiquitin system. We will discuss the rationale for targeting deubiquitylases (DUBs) in cancer and neurodegeneration and for systematic analysis of the family. Illustrative examples of functional studies will include regulation of endocytosis, mitophagy/cell death and hedgehog signaling pathway.
Michael Clague obtained a PhD in biological chemistry from University of Essex. For post-doctoral work he moved to NIH, Bethesda USA to study the biophysics of membrane fusion and later obtained an EMBO long term fellowship to study cell biology (membrane trafficking) at EMBL. He was then appointed to a faculty position at University of Liverpool and is currently Professor of Molecular and Cellular Physiology.
Early work at Liverpool focused on the role of phosphoinositide metabolism along the endocytic pathway. He has defined the endosomal degradation pathway of the c-Met receptor and undertaken further mechanistic studies of EGFR trafficking and signaling. Working together with
Sylvie Urbé he characterised endosomal deubiquitylases, providing the first example of a ubiquitin chain-linkage specific enzyme. This has lead to a broader interest in ubiquitin biology and the deubiquitylase family as potential drug targets. Current work investigates these enzymes in pathways germane to cancer and neurodegeneration, uses mass spectrometry to investigate cell signaling networks and various cell biology approaches to study membrane organisation in breast cancer cells.
Sylvie Urbé obtained a Diploma in Biology from the University of Heidelberg/EMBL where she began to study small GTPases of the rab family. For her post-graduate work, she moved to ICRF, London, UK, where she established an in vitro assay measuring homotypic fusion events between secretory granules in neuroendocrine cells. Her post-doctoral work was conducted at the University of Liverpool, studying the endosomal scaffold protein, HRS, and its role in the regulation of growth factor receptor trafficking. She was able to establish her own laboratory through a Wellcome Trust Career Development Award and a subsequent Cancer Research UK Senior Fellowship, to study the regulation of growth factor receptor trafficking and signalling by endosomal deubiqutylases (DUBs). She is currently Professor of Molecular and Cellular Physiology. Current work is focused on understanding DUB function and validation of these enzymes as potential drug targets.
