Enhanced and Scalable Identification of Malaria Drug Targets Through Conditional Gene Expression

Jacquin Niles of the Massachusetts Institute of Technology in the U.S. is developing a method to switch individual genes on and off in the malaria-causing parasite Plasmodium falciparum for evaluating candidate and existing antimalarial drugs. In Phase I, they built and tested a scalable TetR-aptamer system for rapidly and easily manipulating gene expression in the parasite genome, and showed that it could be used to validate the target of a 4-aminoquinoline antimalarial drug. In Phase II they will use the system to produce a reference panel of over 150 stable parasite lines in which target genes of interest can be conditionally regulated. This resource, which can be expanded, will be valuable for investigating basic parasite biology as well as for drug development. They will use these lines to screen known and candidate antimalarial compounds to identify their targets and help improve their activity.