Regulation of host cell invasion in Toxoplasma parasites
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
| (Primary) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
Details of project
Our lab is offering projects in either Plasmodium falciparum or Toxoplasma. Upon host cell contact, apicomplexan parasites must activate the molecular machinery required for invasion. Evidence is starting to emerge that calcium-mediated signal transduction pathways activate this process. Using the latest genetic techniques, cell biology, proteomics and high-resolution microscopy we have recently revealed a set of molecules that are potentially important components of this invasion-activating pathway. These components include a set of plant-like calcium dependent protein kinases and molecules involved of the inositol phospholipid signalling pathway, all of which represent promising drug targets. PhD/Honours projects are offered in this area and would comprise of functional characterisation of one/some of these components and/or the identification of new molecules involved in the activation of invasion.
Project references
- Nebl, et al (2011) Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex. PLoS Pathogens, In Press (Please email for a copy)
Research interests
The phylum Apicomplexa comprises a group of obligate intracellular parasites of huge medical significance. Toxoplasma, for example, infects between 30-80% of the population and is the cause of toxoplasmosis. Plasmodium parasites on the other hand are the cause of 300 million malaria cases and 3 million deaths a year.
All Apicomplexa must invade host cells for survival and proliferation and thus this process represents an excellent target for new anti-parasitic infection. We are in interested in revealing key molecules that are involved in host cell invasion within these parasites in order to reveal new potential drug targets to combat infection and alleviate the huge burden that these apicomplexan parasites place on human health. Our lab works on both Toxoplasma and Plasmodium falciparum. We work on Toxoplasma, to utilize its superior genetic and cellular tractability. This allows us to reveal molecular detail of apicomplexan invasion at a resolution not possible in any other parasite. Our findings can then be translated into the most deadly of all apicomplexan parasites - P. falciparum.
We use state-of-the-art techniques including; proteomics, microscopy and molecular genetics (transgenic parasites, conditional mutants) to answer our important fundamental questions. Our long-term goal is to rationally identify new molecules that vaccines and drugs could be targeted against to relieve the huge burden that this group of parasites places on humanity.
For more details please see http://www.wehi.edu.au/faculty_members/dr_chris_tonkin.
Selected publications
- Nebl, et al. 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 (Please email for a copy)
- Billker O, Lourido S, & Sibley LD. Calcium-dependent signaling and kinases in apicomplexan parasites. Cell Host Microbe. 2009;5(6):612-622.
- Lourido S, et al. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature. 2010;465(7296):359-362.
Research theme
Infectious diseases
Scientific discipline
- Cell Biology
- Genetics
- Microbiology
- Molecular Biology
- Proteomics
Keywords
Toxoplasma, Plasmodium, malaria, infectious diseases, signal transduction, signaling, invasion, calcium