David Komander

New ubiquitin modifications in mammalian cells analysed by mass-spectrometry
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Ubiquitination affects all cellular pathways, and deregulation of the ubiquitin system is tightly linked to infection, inflammation, neurodegeneration and cancer. Indeed, the ubiquitin system represents a large untapped resource for new therapeutics. Yet, the complexity of the ubiquitin system is high, and indeed it is now currently known how many different ubiquitin modifications exist and are independently used in physiological processes. In particular, discoveries in 2014 by us and others have revealed that ubiquitin is phosphorylated and acetylated, but enzymes that regulate these modification are unknown.

We have recently developed a new method to study ubiquitin modifications in cells comprehensively and with relative ease, using mass-spectrometry. In your PhD, you will identify new ubiquitin modifications, and reveal signalling pathways and cellular contexts in which ubiquitin modifications are upregulated. This part will require you to become an expert in mass-spectrometry, and you will perform experiments on our dedicated instruments. Identification of cellular signalling contexts will enable you to discover machineries that regulate particular ubiquitin modifications in vitro and in vivo. We routinely apply structural biology techniques (X-ray crystallography and NMR), biophysical techniques to study binding partners and enzyme kinetics, cell biological methods and gene targeting techniques (CRISPR/Cas) to interrogate signalling. Your work will break open new areas of ubiquitin biology.


References:

  1. Swatek, K.N. and Komander, D. (2016)
    Ubiquitin modifications
    Cell Res  26(4), 399-422.