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Malaria research close to understanding parasite lifecycle

July 30, 2014

News

Life Sciences

Biological Sciences, Microbiology, Virology

A Nottingham researcher who had malaria seven times as a child is close to understanding the life-cycle of the parasite which causes the disease. Dr Rita Tewari has studied the roles of 30 protein phosphatases and 72 kinases as the malaria parasite develops in the body and then in the mosquito gut. She believes this means her team are closer than ever to disrupting the life-cycle of the malaria-causing parasite. “This latest study identifies how protein phosphatases regulate parasite development and differentiation,” she said. “Our research provides a systematic functional analysis for all 30 phosphatases in Plasmodium berghei – the parasite responsible for causing malaria in rodents. These enzymes work in tandem with the protein kinases identified in a complementary study carried out in 2010. If we can find out what proteins are essential for these parasites to develop and divide, maybe we can target those proteins and arrest them with drugs or vaccines.” Dr Tony Holder, Head of the MRC-NIMR Division of Parasitology, said: “Inhibitors of protein kinases are already used in treatments for other diseases and there is growing interest to develop phosphatase inhibitors as drugs. Identifying the key kinases and phosphatases in the parasite life cycle will define the targets for drug development to treat human malaria and prevent its transmission in communities by the mosquito.” It has taken eight years to identify all the phosphatases and kinases involved in malaria parasite development, and it is still not fully understood. Using a number of molecular cell biology and biochemical techniques, Tewari and her team are trying to understand the basic developmental biology of these parasites.

Malaria mosquitoes in Tewari’s lab. Credit: University of Nottingham.

Half the phosphatases genes (16) could not be knocked out, the team found, suggesting some of these could be future drug targets as their presence is critical to parasite growth. “Interestingly, out of the genes that could be knocked out, six were found to be crucial for sexual development and hence could be drug targets for parasite transmission to and from the mosquito,”Tewari said. There are two dominant types of malaria in humans, Plasmodium vivax which is common in Asia, and Plasmodium falciparum, the most deadly and is rife in Africa. There are currently only two drugs effective against the disease and they are developing resistance. “Resistance to anti-malarial drugs is increasing,” said Tewari. “As a result, the race to uncover new vaccines and more effective drugs to treat disease and block malarial transmission is becoming ever more important.” The work, published in Cell Host and Microbe, was supported by over £1.2m from the Medical Research Council, who are also involved in the research, along with colleagues at the University of Oxford, Imperial College London and King Abdullah University of Science and Technology. Genome-wide Functional Analysis of Plasmodium Protein Phosphatases Reveals Key Regulators of Parasite Development and Differentiation Dr Tewari on her work: