University of Dundee

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. PhD projects are 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 PhD projects 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. We also have projects that will involve the development of efficient platforms for screening and selectivity profiling for small molecule modulators of E3 ligases2

References

  1. Pao, K.-C. et al. Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation. Nature Chemical Biology 12, 324–331 (2016).
  2. Niphakis, M. J. & Cravatt, B. F. Enzyme inhibitor discovery by activity-based protein profiling. Annu Rev Biochem 83, 341–377 (2014).