The Walter and Eliza Hall Institute of Medical Research

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$USD1.05 million award to study liver-stage malaria

 

Malaria researcher Dr Justin Boddey from the Walter and Eliza Hall Institute has won a $USD1.05 million Human Frontier Science Program (HFSP) Young Investigator Grant to study the early stages of malaria infection, in the hopes of finding new ways to treat malaria.

Dr Boddey studies the liver-stages of infection with Plasmodium falciparum, the most deadly form of malaria. The three-year HFSP grant will establish a collaboration between Dr Boddey, from the institute’s Infection and Immunity division, Dr Rhoel Dinglasan from the Johns Hopkins Bloomberg School of Public Health, USA, and Dr Philipp Jost from the Technical University of Munich, Germany.

Dr Boddey said the research team would study the proteins involved in the ‘clinically silent’ liver-stage of infection.

“Prior to the symptomatic blood-stage of malaria, parasites hide and develop in the liver,” Dr Boddey said. “Within minutes of a bite from a parasite-infected mosquito, the parasites invade the liver. They develop here for about a week, before thousands of parasites erupt from the liver and infect the bloodstream, causing clinical symptoms. We are looking for proteins which are essential for parasite stealth in this early stage of infection, that could be a good target for new treatments or whole-organism vaccines to prevent malaria.”

Dr Boddey said malaria was one of the most important parasitic infections of humans.

“Every year more than 250 million people contract malaria and more than one million die, mostly African children. Plasmodium falciparum causes the most severe disease.”

He said a key to the success of P. falciparum infection was the parasite’s ability to evade the immune system. “The parasites develop in the liver without eliciting much of an immune response. Studies that have disarmed the liver-stage parasite through genetic mutation allowed the immune system to kill the parasites, which provided protective immunity against subsequent infection. Identifying proteins involved in the liver-stage of malaria is therefore very important for developing potential vaccines,” Dr Boddey said.

“During the blood stage of malaria infection, parasites live in an isolated compartment in the cell and export several hundred proteins into it to ‘renovate’ it. Prior to this, parasites develop in a similar compartment in liver cells and we are interested in knowing whether the same mechanism occurs. It may be that liver cells are manipulated using the same parasite ‘export machinery’ employed within blood cells,” Dr Boddey said.

The research team is particularly interested in investigating whether exported proteins protect the infected cell from stress and programmed cell death.

“Programmed cell death has developed during evolution to prompt the cell to ‘self-destruct’ when it becomes infected, cancerous or damaged. The ability to block the infected cell from suicide is closely linked to parasite survival and, thus, malaria transmission,” Dr Boddey said.

Professor Phil Hodgkin, head of the institute’s Immunology division, will also collaborate on a $USD1.35 million HFSP research grant led by Professor Ton Schumacher from the Netherlands Cancer Institute in association with Professor Andrew Cohen from the University of Wisconsin – Milwaukee and Dr Ken Duffy from the National University of Ireland, Maynooth. The research team will trace single blood cells from their early stages of development to unravel the cellular and molecular mechanisms that control cell fate.

HFSP research grants are awarded for innovative research projects that involve extensive collaboration among teams of independent scientists working in different countries and in different disciplines.

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