Infectious Diseases
Influenza
Three influenza pandemics killed tens of millions of people in the 20th century. Many important early studies of influenza virus were carried out at the institute and Macfarlane Burnet developed the procedure for growing the influenza virus in chick embryo cavities. The procedure is still in use today to produce influenza vaccine. Milestone discoveries include:
Discovery that influenza virus is an RNA virus that genetically reassorts
- Ada GL, Perry BT (1954) The nucleic acid content of influenza virus. Aust J Exp Biol Med Sci. 1954 32(4):453-68.
- Burnet FM and Lind PE (1949) Recombination of characters between two influenza strains Aust J of Science 12 109
Recognition of the importance of influenza neuraminidase
- Burnet FM (1952) Haemagglutination in relation to host cell-virus infection Ann Rev Microbiology 6 229
- Gottschalk A (1958) Neuraminidase: its substrate and mode of action Advances in Enzymology 20 135 (1958)
Malaria
Malaria has been a scourge of humanity since antiquity and remains so today. More than a third of the world's population is at risk and more than five hundred million people develop clinical malaria each year, with the loss of at least two to three million lives. Malaria is caused by infection with the parasite Plasmodia, which is transmitted between humans by the bite of a female mosquito. Milestone discoveries made at the institute include:
First cloning of blood-stage antigens of the most pathogenic malaria parasite that infects humans, P. falciparum.
The identification of malaria proteins recognised by antibodies from immune individuals led directly to vaccine trials and an explosion in understanding of malaria genes and proteins.
- Kemp DJ, Coppel RL, Cowman AF, Saint RB, Brown GV, Anders RF (1983) Expression of Plasmodium falciparum blood-stage antigens in Escherichia coli: detection with antibodies from immune humans. Proc Natl Acad Sci USA 80(12): 3787-91. PMID: 6304737
Elucidation of the mechanism of resistance of P. falciparum to major antimalarial drugs.
These discoveries have provided the means to detect drug-resistant malaria parasites and monitor their spread, enabling informed selection of the most effective antimalarial drugs for deployment in endemic areas.
- Cowman AF, Morry MJ, Biggs BA, Cross GA, Foote SJ (1988) Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. Proc Natl Acad Sci USA. 85(23):9109-13
- Foote SJ, Thompson JK, Cowman AF, Kemp DJ (1989) Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P falciparum Cell 57(6) 921-930
- Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF. (2000) Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature. 2000 Feb 24;403(6772):906-9. PMID: 10706290
First gene knockout in P. falciparum.
This technological breakthrough initiated reverse genetics in P. falciparum, showed that the malaria protein KHARP is essential for knob formation in infected red cells and provided evidence that the knobs are responsible for cytoadherence in the microvascalature.
- Crabb BS, Cooke BM, Reeder JC, Waller RF, Caruana SR, Davern KM, Wickham ME, Brown GV, Coppel RL, Cowman AF (1997) Targeted gene disruption shows that knobs enable malaria-infected red cells to cytoadhere under physiological shear stress. Cell 89(2):287-96. PMID: 9108483
Identification of glycosotidyl phosphoinositol (GPI) as a toxin in malaria.
This work has opened up a new vaccine approach for malaria.
- Schofield L, McConville MJ, Hansen D, Campbell AS, Fraser-Reid B, Grusby MJ, Tachado SD. (1999) CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science. 283(5399):225-9.
- Schofield L, Hewitt MC, Evans K, Siomos MA, Seeberger PH. (2002) Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 418(6899):785-9. PMID: 12181569
Leishmaniasis
Leishmaniasis affects as many as 12 million people worldwide, with 1.5–2 million new cases each year. It is caused by Leishmania parasites, which are transmitted to humans by the bite of certain species of sand fly. The most common form causes major lesions on the skin and the most severe form affects vital organs and is often lethal. Milestone discoveries include:
Discovery of phosphoglycans as Leishmania ligands for host cells
This work identified a potential ‘Achilles heel’ for the leishmania parasite
- Handman E, Goding JW (1985) The Leishmania receptor for macrophages is a lipid-containing glycoconjugate. EMBO J. 4(2):329-36
- McConville MJ, Bacic A, Mitchell GF, Handman E (1987) Lipophosphoglycan of Leishmania major that vaccinates against cutaneous leishmaniasis contains an alkylglycerophosphoinositol lipid anchor. Proc Natl Acad Sci USA 84(24):8941-5.