Intracellular Targeting of Acyltransferase Enzymes
Supervisors:
Luke Chamberlain, University of Strathclyde
George Baillie, School of Cardiovascular & Metabolic Health, University of Glasgow
Summary:
S-acylation is an essential chemical modification that regulates the localization, stability and functions of a wide range of cellular proteins. S-acylation has also been linked to a range of different diseases and there is growing interest in targeting the “zDHHC” enzymes that mediate S-acylation as a potential novel therapeutic strategy. However, we currently lack an understanding of fundamental aspects of zDHHC enzyme biology and this is essential to resolve if we are to unlock the full therapeutic potential of these enzymes.
An important area of zDHHC enzyme biology that is poorly defined at present is how these enzymes are targeted to specific intracellular compartments including the endoplasmic reticulum, Golgi and endosomes. This project will use a broad range of techniques including chemical biology (click chemistry), microscopy including FRET and super-resolution, and trap-and-release assays to explore mechanisms underpinning zDHHC enzyme targeting. Furthermore, by applying a library of clickable fatty acid probes, the project will also explore how enzyme localization impacts substrate selection. The successful candidate will also receive additional training in data analysis and presentation, and there will be ample opportunities to attend various conferences and meetings.