Center for Animal Biotechnology  CAB : Infectious diseases: Schistosoma research
 
CENTRE FOR ANIMAL BIOTECHNOLOGY  

Schistosoma research

Scope

The aim of this area of research is to identify novel ways of controling Schistosomiasis.

A pair of adult schistosomes

Research outline

Blood flukes that cause schistosomiasis are endemic in 76 countries; it is estimated that as many as 300 million people are infected, and that another 600 million live at risk of infection. The parasitic worms deposit eggs into the blood vessels of the human gut and liver causing chronic inflammation. The disease kills only a small proportion of patients however the long-term pain and suffering creates a huge economic burden on developing countries that surpasses that of most other endemic diseases. Control largely relies on the drug praziquantel however its wide scale use has led to concerns that drug resistance will develop. New Drugs or control strategies will soon be required. In 1994 the World Health Organisation Schistosome Genome Project was initiated aiming at identifying target genes that will enable scientists to develop new drugs and vaccines. It is anticipated the complete genome of the worm will be reported within the next 12 months and methods are desperately needed to determine the importance of each gene in the pathways that may make good candidates for drugs and vaccines aimed at killing the parasite.

Transduction of Schistosoma mansoni using Boudicca

Bernd Kalinna

In our studies we are using an endogenous retrotransposon/retrovirus (Boudicca) of schistosomes that we have identified in the parasite as a vehicle to genetically manipulate the worm. This will help to understand the function and importance of novel antigens that have been discovered by the genome project. To test this method we will use RNA interference (RNAi) to analyse gene function. This technology employs a naturally occurring pathway that uses short RNA molecules to very specifically control the formation of gene products. We propose to construct virus-like elements to deliver these RNAs. The flukes feed on blood and we will inhibit key digestive enzymes to determine if they might make effective targets for drugs and vaccines.

In a parallel project we are also using Mouse Moloney Leukeamia Virus constructs to deliver DNA into schistosomes.

Our research is funded by NH&MRC and NIH.


Schematic representation of transduction of a schistosome cell

Key publications

  • Kines, K. J., Mann, V. H., Morales, M. E., Shelby, B. D., Kalinna, B. H., Gobert, G. N., Chirgwin, S. R. & Brindley, P. J. (2006). Transduction of Schistosoma mansoni by vesicular stomatitis virus glycoproteinpseudotyped Moloney murine leukemia retrovirus. Experimental Parasitology, 112, 209-220.
  • Hartmann S., Sereda M.J., Sollwedel A., Kalinna B.H., Lucius R. (2006). A nematode allergen elicits protection against challenge infection under specific conditions. Vaccine, 24, 3581–3590.
  • Copeland, S. C., Brindley, P. J., Michael, S. F., Johnston, D. A., Williams, D.J., Heyers, O. & Kalinna, B. H. (2003). Boudicca, a retrovirus-like, LTR retrotransposon from the genome of the human blood fluke, Schistosoma mansoni. Journal of Virology, 77, 6153-6166
  • Kalinna, B. H., Brindley, P. J., Wong, J. Y. M., Bogitsch, B. J., King, L. T., Smyth, D. J., Verity, C. K., Abbenante, A., Brinkworth, R. I., Fairlie, D., Smythe, M. L., Milburn, P. J., Bielefeldt-Ohmann, H., Zheng, Y. & McManus, D. P. (2001). Proteolysis of human hemoglobin by schistosome cathepsin D. Mol. Biochem. Parasitol., 112, 125-137.
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