AsPr Tania De Koning-Ward
|Faculty or Division:||Faculty of Health|
|Department:||School of Medicine|
|Campus:||Geelong Waurn Ponds Campus|
|Phone:||+61 3 522 72923 +61 3 522 72923|
- Bachelor of Science, University of Melbourne, 1992
- Doctor of Philosophy, University of Melbourne, 1996
- Graduate Certificate of Higher Education, Deakin University, 2011
Profile of Associate Professor de Koning-Ward
The consistent theme of A/Prof de Koning-Ward’s research has been to investigate virulence mechanisms of, and immunity to human and animal model pathogens, using molecular genetics as a primary tool. A/Prof de Koning-Ward has developed experience in both rodent and human malaria transgenesis systems during postdoctoral stints at Leiden University (The Netherlands) and The Walter and Eliza Hall Institute, the latter commencing with an NHMRC Howard Florey Centenary Fellowship. Following these postdoctoral positions, A/Prof de Koning-Ward was appointed as Senior Lecturer within Deakin University’s Medical School, a combined research and teaching position, with the latter involving the coordination of the Infection, Defence and Repair Unit for 1st year medical students. Since 2011 she has relinquished this teaching component to take up an NHMRC fellowship to expand her independent research program at Deakin University. She was awarded the Commonwealth Health Minister’s Prize for Excellence in Health and Medical Research in 2011.
Malaria is one of the world’s most devastating human health problems, with Plasmodium falciparum, the most lethal of the human malaria species, causing ~660 000 deaths annually. Unfortunately there is no licenced malaria vaccine and resistance to currently available anti-malaria drugs is now very widespread. Thus, there is a desperate need to identify new intervention strategies to reduce the global malaria parasite burden.
The focus of our research is investigations into the virulence mechanisms of, and development of immunity to, malaria parasites using a range of molecular, biochemical and microscopy approaches. We utilise both human (P. falciparum) and rodent (P. berghei) malaria transgenesis systems to genetically modify malaria genes to dissect gene function or to introduce reporter genes to study the localisation of parasite proteins within the infected red blood cell (RBC). The use of both transgenesis systems enables the characterisation of proteins in the clinically relevant human malaria parasite, which is predominantly cultured in blood cells in vitro, and the dissection of the functional significance and contribution of these proteins to pathogenesis and immunity using an in vivo mouse model of malaria infection. By understanding the key mechanisms by which parasites are able to survive within their host and cause disease, we aim to discover new drug targets that can be used to prevent the large morbidity and mortality associated with malaria infections.
We are now recruiting Honours and PhD Students to work on the following project areas. Please email expressions of interest to A/Prof de Koning-Ward.
1. Understanding how malaria parasites remodel their host red blood cell (RBC).
Malaria parasites spend nearly their entire cell cycle within RBCs and to thrive inside the bloodstream the parasites export ~ 8% of their encoded genome (~350 proteins) into the host RBC. Here, the exported proteins are involved in the acquisition of nutrients from host serum or have virulence-associated roles. In 2009, we made a significant breakthrough in our understanding of protein export through the identification of a novel protein machinery that exports parasite proteins into the host RBC (de Koning-Ward et al, Nature, 2009). Since this machinery provides a common portal through which all or most of the exported proteins must pass and these proteins are involved in processes crucial to parasite virulence and viability, this translocon represents an outstanding target for malaria chemotherapeutic intervention. Our work is now aimed at characterising the various components of this machinery so that the mechanistic details of how proteins are trafficked from the parasite and into to RBC can be unravelled.
2. Characterisation of exported proteins
In addition to understanding the trafficking pathways that are used by the malaria parasite to export its proteins into its host cells, we are also characterising different classes of exported proteins to delineate their role in host cell remodelling and pathogenesis.
3. Dissecting the contribution of key malaria proteins to pathogenesis and immune evasion
We use reverse genetics to modify malaria parasites in combination with infection studies, post-genomic, biochemical, and cell biology approaches to identify and validate new drug and vaccine targets.
4. Dissecting the role of rhoptry body proteins in parasite invasion and establishment of new permeation pathways in the infected RBC.
5. Dissecting the molecular mechanisms by which malaria parasites are able to cause severe anemia in susceptible individuals.