Large-scale RNAi screening uncovers therapeutic targets in the parasite Schistosoma mansoni

Jipeng Wang, Carlos Paz, Gilda Padalino, Avril Coghlan, Zhigang Lu, Irina Gradinaru, Julie N.R. Collins, Matthew Berriman, Karl F. Hoffmann, James J. Collins

Research output: Contribution to journalArticlepeer-review

40 Citations (SciVal)
169 Downloads (Pure)

Abstract

Schistosome parasites kill 250,000 people every year. Treatment of schistosomiasis relies on the drug praziquantel. Unfortunately, a scarcity of molecular tools has hindered the discovery of new drug targets. Here, we describe a large-scale RNA interference (RNAi) screen in adult Schistosoma mansoni that examined the function of 2216 genes. We identified 261 genes with phenotypes affecting neuromuscular function, tissue integrity, stem cell maintenance, and parasite survival. Leveraging these data, we prioritized compounds with activity against the parasites and uncovered a pair of protein kinases (TAO and STK25) that cooperate to maintain muscle-specific messenger RNA transcription. Loss of either of these kinases results in paralysis and worm death in a mammalian host. These studies may help expedite therapeutic development and invigorate studies of these neglected parasites.

Original languageEnglish
Article numbereabb7699
Pages (from-to)1649-1653
Number of pages5
JournalScience (New York, N.Y.)
Volume369
Issue number6511
DOIs
Publication statusPublished - 25 Sept 2020

Keywords

  • Animals
  • Anthelmintics/chemistry
  • Genes, Helminth
  • Genetic Testing
  • Helminth Proteins/antagonists & inhibitors
  • Molecular Targeted Therapy
  • Protein Serine-Threonine Kinases/antagonists & inhibitors
  • RNA Interference
  • Schistosoma mansoni/drug effects
  • Schistosomiasis mansoni/drug therapy
  • Transcription, Genetic/drug effects

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