Dr Chris Tonkin
Division: Infection and Immunity
Apicomplexan parasites cause a wide range of disease of medical and agricultural significance. Plasmodium species are the cause of malaria and infect about 300 million people a year killing approximately 2 million. Cryptosporidium parasites inflict severe gastrointestinal disease and are partly responsible for diarrhoea as a leading cause of death in the developing world. Toxoplasma gondii is the most ubiquitous of all Apicomplexa, infecting 30-80 per cent of the world's population. Toxoplasma can cause toxoplasmosis, which normally occurs in immunocompromised individuals such as transplant recipients and AIDS patients. Toxoplasma infection of the eye can cause retinochoroiditis and is a leading cause of blindness in some developing nations.
All apicomplexan parasites must invade their cognate host cells for survival and replication. Plasmodium species are highly selective in the host cells they will invade - for example, hepatocytes in the liver stage or red blood cells in the pathogenic blood stage. Toxoplasma, on the other hand, will invade almost any nucleated cell and often resides in neural and muscle tissue for long-term survival. Although these different parasites use different receptors the common thread between all Apicomplexa is that they all appear to use a conserved set of internal machinery to drive the invasion process. Revealing conserved fundamental aspects of invasion in these parasites might lead to new treatments for diseases such as malaria, cryptosporidiosis and toxoplasmosis.
Apicomplexan invasion comprises a highly complex set of events including recognition of an appropriate host cell, sequential release of invasion organelles and activation of the actin-myosin based invasion machinery. We use the genetic and cellular tractability of Toxoplasma to reveal fundamental aspects of invasion that are common to all Apicomplexan parasites. We then apply this information to Plasmodium falciparum, which is the form of malaria most lethal to humans, to reveal the importance of these novel components in the pathogenesis of this deadly malaria parasite.
We use the latest in proteomics, molecular and cellular biology as well as high end imaging platforms to reveal the processes that mediate host cell invasion and how these take place in time and space.
- Characterisation of molecules controlling the initiation of host cell invasion
- Phosphorylation networks mediating apicomplexan host cell invasion
- Spatiotemporal dynamics of host cell invasion
- Nebl T, Prieto JH, Kapp E, Smith BJ, Williams MJ, Yates 3rdJR, Cowman AF, Tonkin CJ. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex. PLoS Pathogens, 2011 In press
- Foth BJ*, Ralph SA*, Tonkin CJ*, Struck NS, Fraunholz M, Roos DS, Cowman AF, McFadden GI. Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum. Science, 2003. 299(5607): p. 705-8. PMID: 12560551 [PubMed - indexed for MEDLINE]
- Tonkin CJ, Carret CK, Duraisingh MT, Voss TS, Ralph SA, Hommel M, Duffy MF, Silva LM, Scherf A, Ivens A, Speed TP, Beeson JG, Cowman AF. Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum. PLoS Biol. 2009 Apr 14;7(4):e84. PMID: 19402747 [PubMed - indexed for MEDLINE]
- Tonkin CJ, Foth BJ, Ralph SA, Struck N, Cowman AF, McFadden GI. Evolution of malaria parasite plastid targeting sequences. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4781-5. PMID: 18353992 [PubMed - indexed for MEDLINE]
- van Dooren GG*, Marti M*, Tonkin CJ*, Stimmler L, Cowman AF, McFadden GI. Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum. Mol. Micro. 2005, 57(2):405-19. PMID: 15978074 [PubMed - indexed for MEDLINE]
- Tonkin CJ, Roos DS, McFadden GI. N-terminal positively charged amino acids, but not their exact position, are important for apicoplast transit peptide fidelity in Toxoplasma gondii. Mol. Biochem. Parasitol. 2006 Dec;150(2):192-200. PMID: 16963133 [PubMed - indexed for MEDLINE]
- Baum J, Tonkin CJ, Paul AS, Rug M, Smith BJ, Gould SB, Richard D, Pollard TD, Cowman AF. A malaria parasite formin regulates actin polymerization and localizes to the parasite-erythrocyte moving junction during invasion. Cell Host Microbe. 2008 Mar 13;3(3):188-98. PMID: 18329618 [PubMed - indexed for MEDLINE]
- Tonkin CJ, Struck NS, Mullin KA, Stimmler L, McFadden GI. Evidence for Golgi-Independent transport from the early secretory pathway to the plastid in malaria. Mol Micro 2006; 61(3): 614-630. PMID: 16787449 [PubMed - indexed for MEDLINE]
- Tonkin CJ, Kalanon M, McFadden GI. Protein targeting to the malaria parasite plastid. Traffic. 2008 Feb;9(2):166-75. PMID: 17900270 [PubMed - indexed for MEDLINE]
- Bullen HE, Tonkin CJ, O'Donnell RA, Tham WH, Papenfuss AT, Gould S, Cowman AF, Crabb BS, Gilson PR. A novel family of apicomplexan glideosome associated proteins with an inner-membrane anchoring role. J Biol Chem. 2009 Jun 26. [Epub ahead of print] PMID: 19561073 [PubMed - indexed for MEDLINE]
*authors contributed equally
Current Laboratory Members
Faculty Member: Chris Tonkin BSc(Hons) PhD Melb
Postgraduate student: James McCoy BSc(Hons) Melb
Postgraduate student: Rebecca Stewart BSc(Hons) WA
Honours student: Melanie Williams BSc RMIT
UROP Student: Clare Bradin