Synthetic transcriptional control in the malaria parasite Plasmodium falciparum
Malaria is responsible for over half a million deaths each year. However, our understanding of malaria parasite biology is hampered by a lack of molecular tools, particularly at the level of transcriptional control. In light of this, we have created two orthogonal systems for inducible transcriptional repression in the malaria parasite Plasmodium falciparum using bacterial repressor proteins. We…
Malaria claims over half a million lives annually. The complexity of malaria parasite biology is hindered by the absence of molecular tools, particularly concerning transcriptional control. To address this, researchers have developed two independent systems for inducible transcriptional repression in the malaria parasite Plasmodium falciparum, employing bacterial repressor proteins.
These systems achieve a remarkable 200- to 800-fold reduction in gene expression, surpassing previous attempts by two orders of magnitude and outperforming existing translational/post-transcriptional regulation systems.
The team also created automated DNA design software to facilitate the application of this transcriptional repression tool to the conditional regulation of native gene expression in Plasmodium falciparum. This validation confirms the system's utility in essentiality studies and chemogenetic interactions. The system effectively interacts with two parasite lipid kinases and PfKelch13, a protein linked to artemisinin resistance.
By providing these advanced tools, researchers can now enhance their understanding and manipulation of malaria functional genomics, elucidate drug mechanisms, and refine gene regulation strategies.
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