Dr Danny Wilson

Half of the world’s population is at risk of infection with mosquito-borne malaria parasites of the genus Plasmodium. These complex eukaryotic parasites that live inside human cells cause widespread sickness and death throughout tropical and sub-tropical regions of the world including countries neighbouring Australia. The majority of the >400,000 malaria related deaths that occur each year are caused by the parasite Plasmodium falciparum in children under 5 years in Africa, Asia and South America.

Unfortunately, resistance has developed to our most effective anti-malarial drugs, resulting in poorer treatment outcomes for clinical cases of this deadly parasite. There is an urgent need to identify novel drugs to partner with current first-line treatments to fill this looming treatment gap. In addition, development of an effective vaccine would reduce the burden of disease and greatly facilitate efforts to eradicate malaria. Unfortunately, a highly effective vaccine to protect against malaria has not been developed to date and efforts to identify the best vaccine targets are ongoing.

My laboratory seeks to identify and characterise novel parasite proteins for their suitability as both drug and vaccine targets. We focus on invasion of the human red blood cell by the small invasive merozoite stage of the parasite lifecycle as a therapeutic target. By developing therapeutics (drugs and vaccines) that inhibit merozoite invasion of the red blood cell we can instantly disrupt the lifecycle of the parasite in the stage that causes all the symptoms of the disease. We apply a breakthrough P. falciparum merozoite purification method (PNAS, 2010) that is superior to alternatives for studying malaria parasite invasion biology, opening up new opportunities to study this previously intractable lifecycle stage (Figure 1).

Antimalarials that inhibit invasion

By applying state of the art methods, we aim to develop invasion inhibitory antimalarials as viable drugs in a climate of increasing resistance to frontline treatments. Using a highly reproducible flow cytometry approach (Antimicrobial Agents & Chemotherapy, 2013; Figure 2 A & B), we have screened traditional antimalarial therapies, protease inhibitors, kinase inhibitors, a range of antibiotics and identified several compounds and there analogues that rapidly inhibit merozoite invasion (BMC Biology, 2015). To understand how drug-like compounds target the essential process of merozoite invasion, we apply mutation analysis of gene targets, phenotypic screens of related Apicomplexan parasites, modifications and screens of analogues, fluorescence microscopy localisation and proteomic identification of drug binding targets. Importantly, many of the invasion inhibitory compounds identified in our research also kill at other stages of the parasites complex lifecycle, increasing there utility as broad acting antimalarials. Development of these invasion inhibitory compounds and identification of the mechanisms by which they inhibit invasion is the subject of ongoing research in the laboratory.

Functional characterisation of poorly defined merozoite vaccine targets

The function of nearly 50% of the genes in P. falciparum parasites is poorly described or not known altogether. Malaria proteins involved in invasion are no exception with a large number of potential vaccine targets having no known function. We apply gene-editing techniques to examine the potential role of some of these proteins in invasion and parasite growth. Using fluorescence microscopy, flow cytometry, genetic manipulation and proteomic techniques, we are characterising the localisation, interactions and functions of merozoite antigens with no known function to test their suitability as therapeutic targets.

Postgraduate and undergraduate opportunities

Honours, summer-student, masters and PhD projects are available to explore the biology of the malaria parasite and to develop new therapies against this deadly infectious organism. We are a small, supportive, research team that is applying new technologies to discover new ways of ending the burden of malaria disease. If you would like to find out more about our current research opportunities and whether our research is right for you, please contact Dr. Danny Wilson (danny.wilson@adelaide.edu.au).