The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Trends Parasitol. 2022 Feb;38(2):160-173. doi: 10.1016/j.pt.2021.09.002. Epub 2021 Sep 24.
Genome-scale genetic screens allow researchers to rapidly identify the genes and proteins that impact a particular phenotype of interest. In African trypanosomes, RNA interference (RNAi) knockdown screens have revealed mechanisms underpinning drug resistance, drug transport, prodrug metabolism, quorum sensing, genome replication, and gene expression control. RNAi screening has also been remarkably effective at highlighting promising potential antitrypanosomal drug targets. The first ever RNAi library screen was implemented in African trypanosomes, and genome-scale RNAi screens and other related approaches continue to have a major impact on trypanosomatid research. Here, I review those impacts in terms of both discovery and translation.
基因组规模的遗传筛选使研究人员能够快速识别影响特定感兴趣表型的基因和蛋白质。在非洲锥虫中,RNA 干扰 (RNAi) 敲低筛选揭示了耐药性、药物转运、前药代谢、群体感应、基因组复制和基因表达控制的机制。RNAi 筛选在突出有前途的潜在抗锥虫药物靶点方面也非常有效。第一个 RNAi 文库筛选在非洲锥虫中实施,并且基因组规模的 RNAi 筛选和其他相关方法继续对锥虫研究产生重大影响。在这里,我从发现和转化两个方面来回顾这些影响。