Harnessing the power of new genetic tools to illuminate Giardia biology and pathogenesis.

IF 3.3 3区 生物学
Genetics Pub Date : 2024-04-16 DOI:10.1093/genetics/iyae038
Kari D Hagen, Christopher J S Hart, Shane G McInally, Scott C Dawson
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引用次数: 0

Abstract

Giardia is a prevalent single-celled microaerophilic intestinal parasite causing diarrheal disease and significantly impacting global health. Double diploid (essentially tetraploid) Giardia trophozoites have presented a formidable challenge to the development of molecular genetic tools to interrogate gene function. High sequence divergence and the high percentage of hypothetical proteins lacking homology to proteins in other eukaryotes have limited our understanding of Giardia protein function, slowing drug target validation and development. For more than 25 years, Giardia A and B assemblages have been readily amenable to transfection with plasmids or linear DNA templates. Here, we highlight the utility and power of genetic approaches developed to assess protein function in Giardia, with particular emphasis on the more recent clustered regularly interspaced palindromic repeats/Cas9-based methods for knockdowns and knockouts. Robust and reliable molecular genetic approaches are fundamental toward the interrogation of Giardia protein function and evaluation of druggable targets. New genetic approaches tailored for the double diploid Giardia are imperative for understanding Giardia's unique biology and pathogenesis.
利用新的基因工具来阐明贾第虫的生物学和致病机理。
贾第虫(Giardia)是一种流行的单细胞嗜微气肠寄生虫,可引起腹泻病,对全球健康产生重大影响。贾第虫滋养体的双二倍体(本质上是四倍体)对开发分子遗传工具以研究基因功能提出了严峻的挑战。高度的序列差异和与其他真核生物蛋白质缺乏同源性的假定蛋白质的高比例限制了我们对贾第鞭毛虫蛋白质功能的了解,减缓了药物靶点的验证和开发。25 年多来,贾第虫 A 型和 B 型集合体很容易被质粒或线性 DNA 模板转染。在此,我们将重点介绍为评估贾第虫蛋白质功能而开发的遗传方法的实用性和强大功能,尤其是最近基于聚类规则间隔回文重复序列/Cas9的基因敲除和基因敲除方法。稳健可靠的分子遗传方法是研究贾第虫蛋白质功能和评估药物靶点的基础。为双二倍体贾第虫量身定制的新遗传方法对于了解贾第虫独特的生物学和致病机理至关重要。
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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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