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04/02/10
Walter and Eliza Hall Institute researchers have identified a key protein used by the malaria parasite to transform human red blood cells, ensuring the parasite’s survival.
Their discovery means researchers have a clear target against which to develop a new class of anti-malarial drugs that destroy the parasite.
Each year more than 400 million people contract malaria, and more than one million people, mostly children, die from the disease. The most lethal form of the disease is caused by the parasite Plasmodium falciparum, which invades red blood cells and drastically modifies them so it can survive.
Professor Alan Cowman, head of the institute’s Infection and Immunity division, said the parasite remodels the red blood cells by exporting hundreds of so-called ‘effector’ proteins into the cytoplasm of the red blood cell. “These are key virulence proteins that allow the parasite to survive in the human and hide from the human immune system,” Professor Cowman said.
“There has to be a mechanism that allows these effector proteins to be exported but until now we haven’t known what it is.”
Dr Justin Boddey, Dr Tony Hodder, Dr Svenja Gunther, Dr Andrew Pearce and Professor Cowman from the institute, in collaboration with Professor Richard Simpson, Dr Heather Patsiouras and Dr Eugene Kapp of the Ludwig Institute for Cancer Research, Professor Brendan Crabb and Paul Gilson at the Burnet Institute and Dr Tania de Koning-Ward at Deakin University, have identified a protein called Plasmepsin V as being essential for effector proteins to be exported into the red blood cell.
Their research has been published today in the international journal Nature.
Professor Cowman said experimentation had shown that the action of Plasmepsin V on the effector proteins was the first step in priming the proteins to be exported beyond the parasite’s membrane into the red blood cell cytoplasm.
“Plasmepsin V is responsible for determining that all the hundreds of effector proteins are exported. If we could find drugs to block Plasmepsin V the malaria parasite would die,” he said.
Professor Cowman said because Plasmepsin V was a protease it was an attractive drug target. “Drugs that target proteases have been very effective in combating HIV so, by analogy, drugs that impede the function of Plasmepsin V should also show promise,” he said.
The research was funded by the National Institutes of Health, the National Health and Medical Research Council and the Howard Hughes Medical Institute.
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Download high resolution image of Professor Cowman and Dr Boddey Credit: Cameron Wells, Walter and Eliza Hall Institute
Download high resolution artist's impression of the malaria parasite invading a red blood cell Credit: Drew Berry, Walter and Eliza Hall Institute
19/01/10
Walter and Eliza Hall Institute researchers have uncovered a group of proteins that could form the basis of an effective vaccine against malaria.
Presently there is no malaria vaccine available, and these new findings support the development of a vaccine against the blood-stage of malaria.
Malaria is an infection of blood cells and is transmitted by mosquitoes. The most common form of malaria is caused by the parasite Plasmodium falciparum. Malaria parasites burrow into red blood cells by producing specific proteins. Once inside red blood cells, the parasites rapidly multiply, leading to massive numbers of parasites in the blood stream that can cause severe disease and death.
Dr James Beeson, Dr Freya Fowkes and Dr Jack Richards from the institute’s Infection and Immunity division, along with Dr Julie Simpson from the University of Melbourne, have identified proteins produced by malaria parasites during the blood-stage that are effective at promoting immune responses that protect people from malaria illness.
Their findings are published today in the international journal PLoS Medicine.
Drs Fowkes and Beeson identified these proteins by reviewing and synthesising data from numerous scientific studies that had looked at the relationship between antibodies produced by the human immune system in response to malaria infection and the ability of these antibodies to protect against malaria.
Dr Beeson said malaria caused by Plasmodium falciparum was a leading cause of death and disease globally, particularly among young children. “As well as presenting an enormous health burden, malaria also has a major impact on social and economic development in countries where the disease is endemic,” Dr Beeson said. “Vaccines are urgently needed to reduce the burden of malaria and perhaps eventually eradicate the disease.
“A malaria vaccine that stimulates an efficient immune response against the proteins that malaria parasites use to burrow into red blood cells would stop the parasite from replicating and prevent severe illness.”
Dr Fowkes said the review of existing studies had illustrated how little was known about blood-stage malaria proteins and their suitability for use in vaccine development.
“Only about six blood-stage malaria proteins have been well studied out of a potential 100 proteins,” she said. “There is an urgent need for malaria researchers to better coordinate their research efforts on these proteins. This will take us one step closer to developing an effective vaccine.”
The research was funded by the National Health and Medical Research Council of Australia and a Victorian Government Operational Infrastructure Support grant.
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Penny Fannin
Strategic Communications Manager
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Download PLoS Medicine research paper
04/01/10
Malaria researcher Professor Alan Cowman from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, has been awarded the 2010 Howard Taylor Ricketts Award by the University of Chicago.
The annual award recognises outstanding accomplishment in the field of medical sciences. It was established in 1913 in memory of Howard Taylor Ricketts, the University of Chicago scientist who demonstrated that Rocky Mountain spotted fever is transferred to man by ticks.
Professor Cowman joins an illustrious list of recipients of the Howard Taylor Ricketts award. Previous recipients include 1993 Nobel Prize winner Phillip Sharp, who co-discovered split genes; Bert Vogelstein; for his work on the tumour suppressors that protect cells from cancerous growth; and Stanley Falkow, who discovered the molecular nature of antibiotic resistance.
Professor Cowman was selected to receive the Howard Taylor Ricketts award by an interdisciplinary faculty committee of the University of Chicago. He learnt of his selection when he unexpectedly received an email from the committee’s chair, Professor Bernard Roizman. “It was a very nice surprise and a great honour to join a list that includes such stellar scientists,” Professor Cowman said.
For the past 30 years Professor Cowman has studied Plasmodium falciparum, the parasite that causes the most deadly form of human malaria. Each year more than 400 million people contract malaria, and more than one million people, mostly children, die from the disease. “Malaria presents an enormous health burden but also has a major impact on social and economic development in countries where the disease is endemic,” Professor Cowman said. “New therapies are urgently needed.”
Professor Cowman’s research has led to better understanding of how the malaria parasite evades the human immune system as well as anti-malarial drugs. It has also revealed much about how the malaria parasite invades and remodels the human red blood cell. Collectively, this knowledge is being used to identify vaccine and drug candidates against malaria.
As a recipient of the Howard Taylor Ricketts award Professor Cowman will give a named lecture on his research to staff of the University of Chicago’s Division of Biological Sciences and School of Medicine in May 2010. He also receives US$10,000 and a medal.
The lecture will have special significance next year as 2010 marks the 100-year anniversary of Howard Taylor Ricketts’ premature death. Dr Ricketts, after demonstrating that Rocky Mountain spotted fever is transferred to man by ticks, described the small bipolar bodies that cause the disease. Later he found – at the cost of his life – the related organism that causes typhus fever.
For further information
Penny Fannin
Strategic Communications Manager
Ph: +61 3 9345 2345
Mob: 0417 125 700
Email: .(JavaScript must be enabled to view this email address)
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