Monday 1 July 2013 4:51pm
Congratulations to Dr Brian Monk of the SJWRI's Molecular Microbiology research programme on being awarded a three-year Project grant worth $1.19M in the 2013 HRC Funding Round, for his project 'Structure-directed antifungal discovery'. Other named investigators from the SJWRI involved in this project are Professor Richard Cannon and Dr Mikhail Keniya, along with Dr Joel Tyndall of the School of Pharmacy. Dr Monk describes this project as follows:
"There is an urgent need to augment the widely-used and well-tolerated but drug resistance-susceptible triazole drugs with broad-spectrum antifungals that target fungal lanosterol 14-alpha-demethylase (Erg11p) and not human CYP51. We have obtained high-resolution X-ray crystal structures of yeast Erg11p with substrates and triazole inhibitors bound. We will apply our unique knowledge of cytochrome P450 structure and function and use a comprehensive set of screens to identify new antifungals. Our research will confirm key biochemical properties of the enzyme, identify a product egress pathway, and resolve the structures of the Erg11ps of several important fungal pathogens and human CYP51. Computer aided drug design, yeast-based high throughput screens, secondary screens, counterscreens plus a combinatorial chemistry capacity will be used to identify efficiently optimal hits as Erg11p-specific drug candidates. The identification of new classes of antifungals will provide models for drug discovery and development that circumvent the ubiquitous activities of cytochrome P450 enzymes."
Dr Brian Monk (foreground) with Dr Joel Tyndall (background left) and Dr Mikhail Keniya (background right)