Satpal Virdee has been awarded a BBSRC Responsive Mode award of £650,000 allowing his lab to further develop technology they pioneered that enables the activity-based profiling of E3 ligases.

The ubiquitin system is involved in many aspects of cellular biology and defects within this system often give rise to diseases such as cancer, neurodegeneration and autoimmune disorders. E3 ligases confer substrate specificity and have become attractive drug targets. These enzymes demonstrate regulated activity but tools for the multiplexed profiling of their activity on a proteome scale, across broad cell and tissue types, are absent.

Furthermore, 1000's of proteins are known to be ubiquitinated at distinct sites yet our understanding of which of the >600 RING E3 ligases might be responsible is often poor.

This BBSRC award will help Dr Virdee's lab to establish a chemical proteomic platform for profiling E3 ligases, and thereby assign them to diverse (patho)physiological processes. A novel class of probe will also be developed that will covalently crosslink substrates to their cognate RING E3s.

Upon receiving news of the prize Dr Virdee said, 'We, and others, are very excited about the proof of concept work my lab has already carried out and this award will allow us to develop it further. Some aspects of this proposal were high risk and I am delighted that the BBSRC were still prepared to back us.'

Professor Dario Alessi, Director of the MRC unit stated, 'Fantastic news that Satpal has been awarded this highly sought after BBSRC grant to develop new classes of probes to unbiasedly analyse the activity state of E3 ligases. This is an important and innovative project that has the potential to transform our understanding of the regulation and function of E3 ligases in health and disease. I am confident that many future breakthroughs will be made possible by work such as this, which is focused on crafting cutting-edge chemical tools to better interrogate biological pathways'.

Satpal is advertising for PhD students and Postdocs to work on this and other projects in his lab. For enquiries please contact Satpal: s.s.virdee@dundee.ac.uk.