The 'yin and yang' of malaria parasite development
9 Jul 2014
Image © Nottingham University
Scientists searching for new drug and vaccine targets to stop transmission of Plasmodium, the parasite responsible for one of the world’s deadliest diseases, believe they are closer than ever to disrupting its life-cycle.
Dr Rita Tewari at the School of Life Sciences at the University of Nottingham has completed what she describes as a ‘Herculean study’ into the roles played by the 30 protein phosphatases and 72 kinases – enzymes that act as the ‘yin and yang’ switches for proteins – of the malaria parasite as it develops in humans and mosquitoes.
Dr Tewari’s research in funded by the Medical Research Council (MRC) and was carried out in collaboration with the MRC National Institute for Medical Research (MRC-NIMR) in London, together with colleagues at the University of Oxford, Imperial College London and King Abdullah University of Science and Technology, Saudi Arabia, and is published in the academic journal Cell Host and Microbe.
Malaria parasite development and cues controlling the malaria parasite lifecycle are still not fully understood. Dr Tewari’s team is trying to understand the basic developmental biology of these parasites in order to identify new drug targets for malaria. As with so many antimicrobial agents, the malaria parasite has developed resistance to almost all drugs available to treat the disease. This research is therefore more important than ever.
Dr Tewari said:
“This latest study identifies how protein phosphatases regulate parasite development and differentiation. Our research provides a systematic functional analysis for all the 30 phosphatases in Plasmodium berghei – the parasite responsible for causing malaria in rodents. These enzymes work in tandem with the protein kinases identified by the same team 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.”
Using a number of molecular cell biology and biochemical techniques, Dr Tewari and her team found that half the phosphatase genes (16) could not be ‘knocked out’ suggesting some of these genes could be future drug targets as their presence is critical to parasite growth.
Dr Tewari said:
“Interestingly, out of the genes that could be knocked out (14), six were found to be crucial for sexual development and hence could be drug targets for parasite transmission to and from the mosquito. The research gathered here using the mouse malaria parasite can be directly related to the human malaria parasite, as many of the genes in mouse and human malarias are remarkably similar.
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 targets for drug development to treat human malaria and prevent its transmission in communities by the mosquitoes
For further information, contact the MRC press office on +44 (0)20 7395 2345 or email@example.com.
Images are available on request. Please credit The University of Nottingham 2014.
Rita’s laboratory has received over £1.2m from the MRC, UK for its research into malaria parasite biology.