Honorary Associate Professor Brian Monk

Research

It is imperative that new ways are discovered to combat infectious disease, especially where clinically significant drug resistance has emerged. Dr Monk uses molecular genetic manipulation of yeast and bacterial systems to express drug targets for effective screening of compound libraries. Most of the antifungal targets he has developed are membrane proteins. These include essential P-type ATPases, fungal glucan synthase, cytochrome P450 enzymes and drug efflux pumps. Other targets include fungal transcription factors and enzymes involved in fungal riboflavin biosynthesis. For example, we recently determined the X-ray structure of the riboflavin biosynthetic enzyme lumazine synthase from the fungal pathogen Candida glabrata. The challenge of obtaining monodisperse membrane proteins for structurally resolution by X-ray crystallography is well advanced. The structure of yeast lanosterol 14α-demethylase has been determined and other targets of interest are in crystal trials. The yeast expression system patented by Dr Monk in 2003 is used widely to express membrane proteins from a range of sources including pathogenic fungi, plants, and humans. Related research interests include defining and overcoming mechanisms of echinocandin, anthelmintic and antimalarial resistance, expressing human drug targets for drug screening, and equipping yeast biofactories with efflux pumps to improve productivity by protecting against toxic substrates, products, and metabolites.