PhD Opportunity: Structural and Functional Analysis of Metabolic Serine Hydrolases Regulating Dynamic S-acylation

Protein function is tightly controlled in cells to ensure physiological processes are correctly coordinated. One way that proteins regulate their function is through the addition of chemical groups that affect their activity. Fatty-acids are one type of chemical group that are reversibly attached onto proteins in a process termed S-acylation (palmitoylation).

This process is important for human health, as dysregulated S-acylation is linked to diseases such as cancer and diabetes, and brain disorders such as schizophrenia, Huntington’s disease and Alzheimer’s disease. A group of enzymes called ‘ABHD’ proteins have been discovered recently as novel regulators of dynamic protein S-acylation. It is important to identify the proteins these ABHD enzymes modify to explore their potential to be targeted in new drug treatments.

This multi-disciplinary project will combine computational chemistry (including bioinformatics, comparative modelling and molecular dynamic simulations) with recently developed chemical-biology techniques, and cell and molecular biology, to determine how ABHD enzymes coordinate this essential process and to develop compounds that modulate the activity of ABHD enzymes.

Ultimately, this research will explore the potential of these ABHDs as therapeutic targets for the discovery of novel drugs to treat a range of diseases that threaten global human health.