"Illuminating” Ubiquitin-dependent Disease Pathways

Protein ubiquitination is a posttranslational modification which regulates almost all aspects of eukaryotic biology. Defects within this system give rise to numerous diseases including neurodegeneration, inflammation and cancer. We have an incomplete understanding of the ubiquitin system because the protein-protein interactions which orchestrate it cannot be detected by current techniques. Characterization of the ubiquitin-related protein-protein interactions in defined disease-related pathways will further our biological understanding and reveal new drug targets.
This project will use state of the art unnatural amino acid mutagenesis in live mammalian cells allowing the precise incorporation of photocrosslinking amino acids into targeted proteins. These photocrosslinking amino acids can thought of as retracted fishing hooks. Exposing the cells to light leads to exposure of the hook allowing the protein to stably capture any transiently interacting proteins. By using this technology we will be able to detect otherwise intractable information and make significant advances in the field of ubiquitin signalling. This project is multidisciplinary and will involve bacterial /mammalian cell culture, unnatural amino acid mutagenesis in various host organisms, microscopy and mass spectrometry. There is also the option of learning synthetic chemistry techniques.

Please direct any informal enquiries by email to Satpal Virdee ([Email Address Removed])