The Walter and Eliza Hall Institute of Medical Research

Dr Justin Boddey

Details

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Division: Infection and Immunity

Research Overview

Malaria infects hundreds of millions of people all over the world every year, causing severe morbidity and perpetuating the poverty cycle. The World Health Organization estimates that 655,000 people died of malaria in 2010 (with an uncertainty range of 537,000 to 907,000). Research that illuminates precisely how the malaria parasite survives within human cells will help guide the development of new antimalarial therapies and a vaccine.

Malaria parasites live in two human cell types: liver cells and red blood cells. Following a bite from an infected mosquito, parasites quickly home to the liver and invade it. Here they grow silently, developing into tens of thousands of parasites per liver cell without the immune system detecting the infection. This remarkable intracellular secrecy is crucial to the parasite’s success, allowing the parasites to eventually depart the liver, transformed, and ready to find a new home – red blood cells. Inside red blood cells, parasites renovate the cell by exporting several hundred proteins into the cell. This remodeling process is crucial for parasite survival but also causes the red blood cells to become sticky, blocking blood flow and causing death. A key question is whether liver cells are transformed using a similar strategy.

We are interested in understanding how malaria parasites live inside host cells and manipulate their intracellular environment. We study the mechanisms of protein export into host cells and the roles of these important proteins once they reach the host. Our research also involves the development of small molecule inhibitors aimed at blocking protein export, thereby disarming the malaria parasite from modifying their host cells.

We use molecular genetics, cell biology, biochemistry, chemical biology and an insectary to study human and rodent malaria parasites. We welcome applications from prospective Honours and PhD students, or postdoctoral scientists looking to undertake liver-stage malaria research.

The Boddey Laboratory is supported by funding from the ARC, the NHMRC, the Human Frontier Science Program, the CASS Foundation and OzEMalaR.

Research Interests

• The mechanisms of protein export during liver-stage malaria
• Role of exported malarial proteins in modifying infected liver cells
• Molecular mechanisms of cell traversal by Plasmodium falciparum
• Plasmepsin V inhibitors as new protein export-blocking antimalarial agents
• Understanding how effector proteins are exported to the malaria-infected erythrocyte (with Professor Alan Cowman)

Selected Publications

1. Boddey JA, Carvalho TG, Hodder AN, Sargeant TJ, Sleebs BE, Marapana D, Lopaticki S, Nebl T, Cowman AF. Role of Plasmepsin V in Export of Diverse Protein Families from the Plasmodium falciparum Exportome. Traffic. 2013 Feb 6. doi: 10.1111/tra.12053. [Epub ahead of print] PMID: 23387285
2. Wawra S, Agacan M, Boddey JA, Davidson I, Gachon CM, Zanda M, Grouffaud S, Whisson SC, Birch PR, Porter AJ, van West P. Avirulence protein 3a (AVR3a) from the potato pathogen Phytophthora infestans forms homodimers through its predicted translocation region and does not specifically bind phospholipids. J Biol Chem. 2012 Nov 2;287(45):38101-9. PMID: 22977236
3. Kappe SHI, Vaughan AM, Boddey JA, Cowman AF. That Was Then But This Is Now: Malaria Research in the Time of an Eradication Agenda. Science. 2010;328: 862-6. PMID: 20466924
4. Boddey JA, Hodder AN, Gunther S, Gilson PR, Patsiouras H, Kapp EA, Pearce JA, de Koning-Ward TF, Simpson RJ, Crabb BS, Cowman AF. An aspartyl protease directs malaria effector proteins to the host cell. Nature. 2010;463: 627-31. PMID: 20130643
5. deKoning-Ward TF, Gilson PR, Boddey JA, Rug M, Smith BJ, Papenfuss AT, Sanders PR, Lundie RJ, Maier AG, Cowman AF, Crabb BS. A newly discovered prtein export machine in malaria parasites. Nature. 2009;459: 945-9. PMID: 19536257
6. Richard D, Kats LM, Langer C, Black CG, Mitri K, Boddey JA, Cowman AF and Coppel RL. Identification of rhoptry trafficking determinants and evidence for a novel sorting mechanism in the malaria parasite Plasmodium falciparum. PLoS Pathogens. 2009;5: e1000328. PMID: 19266084
7. Boddey JA, Moritz RL, Simpson RJ, Cowman AF. Role of the Plasmodium export element in trafficking parasite proteins to the infected erythrocyte. Traffic. 2009;10: 285-99. PMID: 19055692

Click here to view more PubMed publications

Current Laboratory Members

Laboratory Head: Justin Boddey, BBiomedSc(Hons) PhD Griffith

Senior Postdoctoral Fellow: Brad Sleebs, BSc(Hons) PhD LaT

Postdoctoral Fellow: Jennifer Armistead, BSc George Mason MSc Florida PhD MPH Johns Hopkins

Research Assistant: Matthew O'Neill, BSc(Hons) Melb

Research Assistant: Sash Lopaticki, BSc(Hons) VUT

PhD Student: Pravin Rajasekaran, BBiomed(Hons) Melb

PhD Student: Michelle Gazdik, BMedChem(Hons) LaT/Melb

PhD Student: Annie Yang, BBiomedSc(Hons) Auckland