A chemical biology approach to identify novel substrates of the cell surface protein acyl transferase ZDHHC5
Supervisors:
Prof Nicholas C.O. Tomkinson, University of Strathclyde
Prof Will Fuller, University of Glasgow
Summary:
A prominent protein modification found in all eukaryotic species is S-acylation, the attachment of hydrophobic acyl chains onto cysteine side chains. S-Acylation regulates the localisation, stability, interactions, and function of numerous proteins, and thereby affects cellular processes like growth, migration, differentiation, and communication. S-Acylation is reversible and is regulated by many zDHHC (on) and APT/ABHD (off) enzymes, however, in contrast to many other enzymes that mediate the post-translational regulation of proteins, we currently lack fundamental knowledge about these proteins and their contribution to cell physiology.
This project will provide training in synthetic chemistry, chemical biology, cell biology and biological assays to enable the dissection and understanding of the substrate network of the acyl transferase enzyme zDHHC5. You will design, prepare and deploy novel tool compounds and adopt cutting-edge molecular and cellular analyses through an ambitious research programme to define the substrate network of an individual S-acylation enzyme. The complementary expertise of the supervisory team will allow you to tackle this fundamental question through interdisciplinary research and provide the foundation for the translation of these enzymes to validated targets for drug discovery. The project will provide you the skill set necessary to pursue a rewarding career at the chemistry-biology interface.