Large-scale RNAi screening uncovers therapeutic targets in the parasite <em>Schistosoma mansoni</em>

doi:10.1126/science.abb7699

GSTDTAP > 气候变化

DOI	10.1126/science.abb7699
	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
	2020-09-25
发表期刊	Science
出版年	2020
英文摘要	Schistosomiasis is caused by a parasitic flatworm about which little is known. Therefore, options to combat human disease caused by schistosome infection are limited. To aid in our quest to develop treatments, two studies undertook molecular investigations of the parasite Schistosoma mansoni . By generating a single-cell atlas, Wendt et al. identified the developmental trajectory of the flatworm, including the blood-feeding gut required for its survival in the host. From these data, they found a gene required for gut development that, when knocked out through RNA interference, confers reduced pathology in infected mice. Wang et al. performed a large-scale RNA interference survey of S. mansoni and identified an essential pair of protein kinases that can be targeted by approved pharmacological intervention (see the Perspective by Anderson and Duraisingh). These molecular investigations add to our understanding of the schistosome parasite and provide biological information that may help to combat this neglected tropical disease. Science , this issue p. [1644][1], p. [1649][2]; see also p. [1562][3] 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. [1]: /lookup/doi/10.1126/science.abb7709 [2]: /lookup/doi/10.1126/science.abb7699 [3]: /lookup/doi/10.1126/science.abe0710
领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：40[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/296530
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jipeng Wang,Carlos Paz,Gilda Padalino,et al. Large-scale RNAi screening uncovers therapeutic targets in the parasite Schistosoma mansoni[J]. Science,2020.
APA	Jipeng Wang.,Carlos Paz.,Gilda Padalino.,Avril Coghlan.,Zhigang Lu.,...&James J. Collins.(2020).Large-scale RNAi screening uncovers therapeutic targets in the parasite Schistosoma mansoni.Science.
MLA	Jipeng Wang,et al."Large-scale RNAi screening uncovers therapeutic targets in the parasite Schistosoma mansoni".Science (2020).