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基因组学和遗传学方法在抗疟药物耐药性和疟原虫生物学研究中的应用。

Genomic and Genetic Approaches to Studying Antimalarial Drug Resistance and Plasmodium Biology.

机构信息

Department of Microbiology & Immunology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Department of Microbiology & Immunology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.

出版信息

Trends Parasitol. 2021 Jun;37(6):476-492. doi: 10.1016/j.pt.2021.02.007. Epub 2021 Mar 11.

Abstract

Recent progress in genomics and molecular genetics has empowered novel approaches to study gene functions in disease-causing pathogens. In the human malaria parasite Plasmodium falciparum, the application of genome-based analyses, site-directed genome editing, and genetic systems that allow for temporal and quantitative regulation of gene and protein expression have been invaluable in defining the genetic basis of antimalarial resistance and elucidating candidate targets to accelerate drug discovery efforts. Using examples from recent studies, we review applications of some of these approaches in advancing our understanding of Plasmodium biology and illustrate their contributions and limitations in characterizing parasite genomic loci associated with antimalarial drug responses.

摘要

近年来基因组学和分子遗传学的进展为研究致病病原体中的基因功能提供了新的方法。在人类疟疾寄生虫疟原虫中,基于基因组的分析、靶向基因组编辑以及允许基因和蛋白质表达的时间和定量调节的遗传系统的应用,对于确定抗疟药物耐药性的遗传基础和阐明候选靶点以加速药物发现工作具有重要意义。我们使用最近的研究实例,回顾了这些方法中的一些在推进我们对疟原虫生物学的理解方面的应用,并说明了它们在描述与抗疟药物反应相关的寄生虫基因组位点方面的贡献和局限性。

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本文引用的文献

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Genomic Approaches to Drug Resistance in Malaria.基因组学方法在疟疾耐药性中的应用。
Annu Rev Microbiol. 2020 Sep 8;74:761-786. doi: 10.1146/annurev-micro-012220-064343.
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Humanized Mice and the Rebirth of Malaria Genetic Crosses.人源化小鼠与疟疾基因杂交的重生。
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