Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis

Zhang, M. et al. (2018) Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science, 360(6388), eaap7847. (doi: 10.1126/science.aap7847) (PMID:29724925)

Abstract

Malaria is caused by eukaryotic Plasmodium spp. parasites that classically infect red blood cells. These are difficult organisms to investigate genetically because of their AT-rich genomes. Zhang et al. have exploited this peculiarity by using piggyBac transposon insertion sites to achieve saturation-level mutagenesis for identifying and ranking essential genes and drug targets (see the Perspective by White and Rathod). Genes that are current candidates for drug targets were identified as essential, in contrast to many vaccine target genes. Notably, the proteasome degradation pathway was confirmed as a target for developing therapeutic interventions because of the several essential genes involved and the link to the mechanism of action of the current frontline drug, artemisinin.

• Item Type: Articles
• Additional Information: This work was supported by the Wellcome Trust grant 098051 (J.C.R.), the National Institutes of Health grants R01 AI094973, R01 AI117017 (J.H.A.), and F32 AI112271 (J.O.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas
• Authors: Zhang, M., Wang, C., Otto, T. D., Oberstaller, J., Liao, X., Adapa, S. R., Udenze, K., Bronner, I. F., Casandra, D., Mayho, M., Brown, J., Li, S., Swanson, J., Rayner, J. C., Jiang, R. H. Y., and Adams, J. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Science
• Publisher: American Association for the Advancement of Science
• ISSN: 0036-8075
• ISSN (Online): 1095-9203
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Science 360(6388): eaap7847
• Publisher Policy: Reproduced in accordance with the publisher copyright policy