Activity-based Profiling of E3 Ligases

E3 ligases impart the specificity in ubiquitin attachment and are also dysregulated in a number of diseases. As a result, E3s have become attractive therapeutic targets. A PhD project is available in the Virdee lab working on the application and further development of revolutionary new chemical probe technology. We have devised activity-based probes which can be used to profile the activity of ~50 E3 ligases in a single experiment1. E3 activity is typically regulated by posttranslational mechanisms and is difficult, if not impossible, to measure by conventional proteomic and transcriptomic approaches. Our probes provide a unique opportunity to study the regulation of E3 activity in a number of disease-relevant contexts such as cancer, autoimmunity and neurodegeneration2.

We have a PhD project that will apply our technology for the identification of aberrantly activated E3s that are present in disease-relevant cellular systems thereby gaining biological insight and potentially uncovering novel therapeutic targets.