Scientists at Nottingham University and the Wellcome Trust Sanger Institute near Cambridge have pinpointed the 72 molecular switches that control the three key stages in the life cycle of the malaria parasite, and discovered that over a third of these can be disrupted in some way, providing a number of potential new targets to control transmission of the disease.
Until now little was known about the cellular processes involved in the development of the disease. The research involved the very first comprehensive functional analysis of protein kinases in any malaria parasite. It is also the largest gene knock-out study in Plasmodium berghei, a malaria parasite that infects rodents.
Rita Tewari of the School of Biology at Nottingham, who led the research, said blocking parasite transmission is recognised as an important element in the global fight to control malaria. “Kinases [...] contribute to the control of nearly all cellular processes and have already become major drug targets in [...] cancer and other diseases. Now we have identified some key regulators that control the transmission of the malaria parasite.”
Tewari said work to develop drugs to eradicate malaria can now focus on the best targets. “This study shows how systematic functional studies not only increase our knowledge in understanding complexity of malaria parasite development but also gives us the rational approach towards drug development.”
The life cycle of the malaria parasite is complex. Once the mosquito has feasted on infected blood, fertilisation takes place within the mosquito. The parasites are then injected back into another host in large numbers when the mosquito bites again. Once inside its mammalian host, the parasite first infects the liver where it replicates again. After 48 hours millions of parasites are released into the red bloods cells of its host where they produce high fever and sickness.
Oliver Billker, an expert in pathogen genetics at the Wellcome Trust Sanger Institute, said, “This is a major leap forward. We can now set aside 23 functionally redundant genes. This act of prioritisation alone has narrowed the set of targets for drug searches by a third. Our study demonstrates how a large-scale gene knockout study can guide drug development efforts towards the right targets.References
The Systematic Functional Analysis of Plasmodium Protein Kinases Identifies Essential Regulators of Mosquito TransmissionTewari, R. et al.
Cell Host & Microbe, Volume 8, Issue 4, 377-387, 21 October 2010
http://dx.doi.org/10.1016/j.chom.2010.09.006
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