What makes Toxo tick?
Our interests are not limited to apicoplasts and mitochondria. Toxoplasma and related apicomplexan parasites are fascinating parasites. They get their name from the presence of a distinctive apical complex that serves as an invasion machine to enable the parasites to gain entry into their hosts. They contain many other unique, unusual and uncharacterised organelles and cellular structures. Their intracellular existence means that much of their metabolism can be acquired from their host organisms, and in many cases these metabolites can either replace or complement the parasite’s existing biochemical pathways. Elucidating the role of these unique aspects of parasite biology promises to reveal novel therapeutic targets. We apply our expertise in cell biology and parasite genetics in examining diverse biological processes, and always welcome new ideas to use Toxoplasma as a model to characterise unique aspects of parasite biology.
Some examples of the types of projects we are currently working on include:
- Characterising novel vacuoles in Toxoplasma parasites. We recently initiated a project to characterise the Toxoplasma homologue of the chloroquine-resistance transporter (TgCRT), a transport protein that functions in mediating resistance of the malaria-causing parasite Plasmodium to chloroquine, a major anti-malarial drug. TgCRT localises to an intriguing set of intracellular vesicles, the function(s) and importance of which are not known (see image; courtesy of Sally Warring). They are often highly motile within the parasite, are possibly acidic, and undergo a series of rapid changes (becoming smaller and greater in number) following invasion of a parasite into a new host cell. We are now commencing a series of experiments to better characterize these unique organelles.
- Characterising the role of Toxoplasma proteins that contain repeat amino acid motifs. We work in collaboration with Ross Waller’s group in the School of Botany at the University of Melbourne to characterise Toxoplasma proteins that contain amino acid repeat elements in their protein structure. This project stems from work done in the Waller group to characterise amino acid repeat motif-containing proteins in cilates (distant cousins of Apicomplexa). When we localised homologues of these proteins in Toxoplasma, they revealed a fascinating localisation to the apical complex of these parasites, suggesting they may have a role in parasite invasion. We are now further characterising the role of these and other amino acid repeat motif-containing proteins, as well as examining the functions of the amino acid repeat elements in these proteins.
Recent papers from these projects that summarise the sorts of questions we are interested in:
- Gould SB, Kraft LG, van Dooren GG, Goodman CD, Ford KL, Cassin AM, Bacic A, McFadden GI, Waller RF (2011) Ciliate pellicular proteome identifies novel protein families with characteristic repeat motifs that are common to alveolates. Mol Biol Evol 28(3): 1319-31.
- van Dooren GG, Ralph SA (2010) Novel vacuoles in Toxoplasma. Mol Microbiol 76(6): 1335-9
- Striepen B, Jordan CN, Reiff S, van Dooren GG (2007) Building the perfect parasite: cell division in Apicomplexa. PLoS Pathogens, 3(6): e78