Super macrophages: new drugs that up regulate nitric oxide and enhance killing of tuberculosis and other bacteria

Our group has developed the first inhibitors of the nitric oxide-regulating protein family known as SPSB. These inhibitors cause increased NO levels in macrophages and improve macrophage killing of bacteria, including M. tuberculosis. Tuberculosis is a devastating disease that infects one third of the world’s population. Tuberculosis is resistant to all known antibiotics and until now there has been no effective treatment for sufferers of this disease. We are currently developing a range of SPSB inhibitors that include cyclic peptides and small molecules. This project will involve a synthetic component but may, depending on the student’s interests, include some computational modeling or chemical biology such as synthetic membrane permeability assays and surface plasmon resonance experiments.

We are also developing a new polymer-based drug delivery system that selectively delivers our new inhibitors to macrophages. This arm of the project involves synthesise of fluorescent molecular tools for cell targeting and controlled endosomal release. This work will involve the analysis of fluorescent constructs in macrophages using live fluorescence imaging. An Honours student embarking on this projecting can expect to acquire a good grounding in peptide chemistry and small molecule chemistry as well as a good understanding of the drug discovery process and the dynamics of an interdisciplinary research group.