A synthetic biology platform for malaria parasites based on orthogonal transcriptional control

Abstract

Malaria is responsible for half a million deaths each year in some of the poorest communities around the world. Furthermore, the evolution of drug resistance among malaria parasites threatens to continue this trend. However, our understanding of malaria parasite biology is held back by a lack of tools with which to study the function of their genes. In light of this, we have created systems that control gene expression in the malaria parasite Plasmodium falciparum using bacterial repressor proteins. These are the first tools to reliably control malaria parasite transcription and offer the most robust method of conditional gene expression in Plasmodium parasites to date. We develop automated DNA design software to apply this technology to study essential parasite genes for functional genomics and confirm compound-protein interactions for drug discovery. We hope these tools advance efforts to engineer and control malaria parasites in the future.