Prof. Tania F. de Koning-Ward

School of Medicine, Deakin university, Geelong, Victoria, Australia

Prof. Tania F. de Koning-Ward

School of Medicine, Deakin university, Geelong, Victoria, Australia

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Academic Career Length

33Years (1994-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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18 June 2009 in Nature

Journal Article

A newly discovered protein export machine in malaria parasites

Tania F. de Koning-Ward

Paul R. Gilson

Justin A. Boddey

Melanie Rug

Brian J. Smith

Brendan S. Crabb

Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. The trafficking machinery responsible for this export is unknown. Here we identify in Plasmodium falciparum a translocon of exported proteins (PTEX), which is located in the vacuole membrane. The PTEX complex is ATP-powered, and comprises heat shock protein 101 (HSP101; a ClpA/B-like ATPase from the AAA+ superfamily, of a type commonly associated with protein translocons), a novel protein termed PTEX150 and a known parasite protein, exported protein 2 (EXP2). EXP2 is the potential channel, as it is the membrane-associated component of the core PTEX complex. Two other proteins, a new protein PTEX88 and thioredoxin 2 (TRX2), were also identified as PTEX components. As a common portal for numerous crucial processes, this translocon offers a new avenue for therapeutic intervention.

4 February 2010 in Nature

Journal Article

An aspartyl protease directs malaria effector proteins to the host cell

Justin A. Boddey

Anthony N. Hodder

Svenja Günther

Paul R. Gilson

Heather Patsiouras

Alan F. Cowman

Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease.

16 July 2014 in Nature

Journal Article

PTEX is an essential nexus for protein export in malaria parasites

Brendan Elsworth

Kathryn Matthews

Catherine Q. Nie

Ming Kalanon

Sarah C. Charnaud

Tania F. de Koning-Ward

+11

15 January 2006 in Nature Immunology

Journal Article

Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity

Nicholas S Wilson

Georg M N Behrens

Rachel J Lundie

Christopher M Smith

Jason Waithman

Jose A Villadangos

+10

18 June 2001 in Journal of Experimental Medicine

Journal Article

Antibodies against Merozoite Surface Protein (Msp)-119 Are a Major Component of the Invasion-Inhibitory Response in Individuals Immune to Malaria

Rebecca A. O'DOnnell

Tania F. de Koning-Ward

Rachel A. Burt

Moses Bockarie

John C. Reeder

Brendan S. Crabb

Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-1₁₉ from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-1₁₉, we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum–immune humans and P. chabaudi–immune mice. In some individual human sera, MSP-1₁₉ antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-1₁₉–based vaccines.

23 September 2008 in Proceedings of the National Academy of Sciences

Journal Article

Blood-stage Plasmodium infection induces CD8 ⁺ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α ⁺ dendritic cells

Rachel J. Lundie

Tania F. de Koning-Ward

Gayle M. Davey

Catherine Q. Nie

Diana S. Hansen

William Ross Heath

Although CD8 ⁺ T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ECM). At present, there is no direct evidence that the CD8 ⁺ T cells mediating ECM are parasite-specific or, for that matter, whether parasite-specific CD8 ⁺ T cells are generated in response to blood-stage infection. To resolve this and to define the cellular requirements for such priming, we generated transgenic P. berghei parasites expressing model T cell epitopes. This approach was necessary as MHC class I-restricted antigens to blood-stage infection have not been defined. Here, we show that blood-stage infection leads to parasite-specific CD8 ⁺ and CD4 ⁺ T cell responses. Furthermore, we show that P. berghei -expressed antigens are cross-presented by the CD8α ⁺ subset of dendritic cells (DC), and that this induces pathogen-specific cytotoxic T lymphocytes (CTL) capable of lysing cells presenting antigens expressed by blood-stage parasites. Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM.

About Me

Prof. Tania de Koning-Ward is a Professor of molecular microbiology in the School of Medicine and the Deakin Institute for Mental and Physical Health and Clinical Translation at Deakin University. She is currently the leader of the Infection, Immunity, and Cancer Theme at IMPACT, and she also heads a vibrant research team of postdocs, research assistants, PhDs, and honours students focused on understanding the molecular basis of malaria. She has been awarded the Commonwealth Health Minister’s Prize for Excellence in Health and Medical Research (2011), the Smart Geelong Network Biotechnology Award (2012), the Smart Geelong Network Researcher of the Year Award (Highly Commended) (2012), the Deakin University Health Faculty Award for Innovation in Teaching (2012), an NHMRC Senior Research Fellowship (2018–2022) as well as the Australian Society for Parasitology ‘Bancroft Mackerras’ Medal for Excellence. Her research is focussed on investigations into the mechanisms by which pathogens, particularly Plasmodium parasites that cause malaria, can survive and evade the host immune response to cause disease. Her research uses sophisticated molecular genetics, biochemical and cell biology techniques, as well as animal models as core tools.

Prof. Tania F. de Koning-Ward

Prof. Tania F. de Koning-Ward

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