Identification, characterisation and validation of microbial drug targets.
Current antimicrobial therapies such as antibiotics and antivirals are increasingly becoming redundant due to the rapid development of anti-microbial resistance (AMR).
This global phenomenon could potentially result in deaths from infectious diseases increasing to 10 million per year in 2050 (Review on Antimicrobial Resistance, O’Neill, 2014). The issue is heightened because of the very small numbers of new antimicrobials that are currently in development and in preclinical stages. This emphasises need to identify new antimicrobial targets for the generation of new antimicrobials is essential.
This research seeks to understand specific bacterial components that are known to cause disease in humans. This involves proteins within the bacterial cells that are important for bacterial cell wall formation, survival and ability to infect humans.
These proteins are characterised at the molecular and cellular levels to gain a detailed understanding of how they function in bacteria. Furthermore the structures of the proteins are solved and then assessed as targets in a drug discovery pipeline.
Drug discovery and screening
This research seeks to identify and/or design novel drugs to our bacterial targets and test the effect of these drugs against our pathogens of interest.
The drug discovery pipeline has been formed in collaboration with world leading experts in chemical synthesis and medicinal chemistry at the University of Wurzburg and experts in protein engineering in Seattle Structural Genomics Center for Infectious Diseases (SSGCID). This research group has established a range of infection models to test novel inhibitors in diseases including melioidosis, and a range of bacteria that causes pneumonia.
In collaboration with A/Prof Charlene Kahler, we have developed meningococcal and gonococcal infection models and with A/Prof Chris Peacock we have been investigating cell leishmaniasis infection models. This enables us to test the broad spectrum activity of the novel inhibitors against a range of tropical and medically important pathogens that can cause human diseases.
Once a promising drug candidate has been validated, the next stage involves testing in whole systems. We are in the fortunate position to be able to participate in such studies with my collaborator Prof Tim Atkins at Defence Science Technology Laboratory, UK.