Investigating the biological consequences of genetic variation in Plasmodium populations
The Plasmodium parasites that cause malaria have a remarkable talent for survival. They can evade the human immune system, develop resistance to antimalarial drugs, and cope with changes in the Anopheles vector and other environmental fluctuations. This biological tenacity stems from the continual accumulation of small variations in the parasite genome, which allows the parasite population to adapt to new circumstances by evolutionary selection.
The continual evolution of the parasite genome is a major obstacle to malaria control. MalariaGEN investigators are working on different aspects of this problem in four projects:
- Plasmodium falciparum Community Project
- Plasmodium falciparum genetic crosses
- Plasmodium vivax genome variation
The rapid pace of progress in genome sequencing technology coupled with advances in statistics and informatics have transformed our ability to study genetic variation in Plasmodium parasites. We’ve also developed methods for deep sequencing of Plasmodium parasites extracted from blood samples drawn from infected patients. Taken together, these advances are paving the way for large-scale, high-resolution monitoring of genetic variation in malaria parasites.
Through our multi-centre projects, MalariaGEN provides malaria researchers around the world with access to these new technologies, allowing them to investigate the biological consequences of genetic variation in Plasmodium populations at the level of the whole genome. Together, we're building rich data resources and using them to characterise parasite genome variation in different geographical locations and under recent evolutionary selection, as well as investigating factors that determine gene flow between locations, such as rates of inbreeding and population structure.
Our long-term goal is using this information to develop more effective methods of surveillance for the emergence and spread of drug resistance, and, when a malaria vaccine is introduced, to provide early warning of parasite mutations that might render it ineffective. Forewarned is forearmed, and we aim to improve the sustainability and efficacy of malaria control measures by providing public health agencies with real-time information about how parasite populations are evolving.
- Miotto O. et al. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat. Genet. 2013 Apr 28;45(6): 648-5. PMID 23624527
- Manske M., Miotto O. et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature. 2012 July 19; 487: 375-379. PMID 22722859