Exploring enzyme-substrate S-acylation networks and their role in cell physiology

Supervisors: 

Prof Luke Chamberlain, Strathclyde Institute of Pharmacy and Biomedical Sciences (University of Strathclyde)

Prof Helen Walden, School of Molecular Biosciences, (University of Glasgow)

Prof Will Fuller, School of Cardiovascular and 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. The importance of S-acylation is highlighted by links to a range of different diseases including cancer and neurological conditions, and there is growing interest in targeting the “zDHHC” enzymes that mediate S-acylation as a potential novel therapeutic strategy. However, there are several thousand S-acylated proteins that are modified by 23 distinct zDHHC enzymes and we lack an understanding of the substrate networks of individual enzymes and how enzyme-substrate specificity is achieved. This knowledge is essential if we are to unlock the full therapeutic potential of these enzymes. The successful candidate will address these questions using a range of molecular and cellular techniques including click chemistry, confocal microscopy, protein interaction analysis and enzyme-substrate network mapping. There will be opportunities throughout the PhD to present research findings at national and international meetings, to engage with scientists from other disciplines, participate in outreach, and undertake other professional development activities, providing a broad range of relevant training.