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Corporate entry Infection and Immunity Division (1996 - )

The Walter and Eliza Hall Institute of Medical Research

From
1996
Functions
Medical Research
Website
http://www.wehi.edu.au/research/divisions/inf/index.html

Summary

The Infection and Immunity Division took over from the Immunoparasitology Unit in 1996/1997. Today the Division's major research areas are in disease mechanisms and vaccines, functional parasite genomics and parasite cell biology. The goal of this Division is to improve methods for preventing and treating two important parasitic diseases - malaria and leishmaniasis. By developing a better understanding of the basic mechanisms of immunology, cell biology and genetics of these parasites, the Division hopes to develop vaccines and novel chemotherapeutic treatments.

Details

In 1996/97 the Infection and Immunity Division achieved the first gene knockout in P. Falciparum malaria. The technology used has allowed the Division to assess candidate vaccine molecules. One such candidate is glycosylphosphatidylinositol (GPI), the major toxin released by the malaria parasite. The Division demonstrated that vaccination with a synthetic form of GPI protects mice from severe malaria. In 1997/98 the Division, in collaboration with the Papua New Guinea Institute of Medical Research, ran trials in PNG on another candidate malaria vaccine. That same year the Division set about defining the molecular mechanisms of malarial resistance to the sulfa group of drugs. In 1999/2000 the Division began a new initiative, with the Biomolecular Research Institute, to determine the 3-dimensional structure of malaria antigens.

When human erythrocytes become infected by the malaria parasite P falciparum they gain the ability to adhere to organs such as the brain. This cytoadherence is an important factor in deaths caused by malaria. The Infection and Immunity Division has identified elements which bring about these alterations in infected erythrocytes. They also showed that parasite-derived structures, known as Maurer's clefts, are important in assembling the cytoadherence complex. The role of cytokines and their regulation in promoting fatal cerebral malaria in a mouse model is another area of research within the Division.

The Division's work on leishmaniasis focuses on the molecules used by the parasite to over-ride the host immune responses. It also looks at those host genes involved in determining resistance or susceptibility to infection. The main group of genes studied encode a group of proteophosphoglycans (PPGs) and have been shown to subvert the function of macrophages and exacerbate disease. In collaboration with the Genetics and Bioinformatics Division, the three genetic loci involved in susceptibility to leishmaniasis in a mouse model have been mapped. Development of a nucleic acid prophylactic and therapeutic vaccine for leishmania continues.

Published resources

Online Resources

Emily Geraghty & Annette Alafaci