Recent advances in functional research in Giardia intestinalis.
Recent advances in functional research in Giardia intestinalis.
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DOI：
10.1016/bs.apar.2019.12.002
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发表时间：
2020
影响因子：
--
通讯作者：
Dawson SC
中科院分区：
文献类型：
--
作者：
Jex AR;Svärd S;Hagen KD;Starcevich H;Emery-Corbin SJ;Balan B;Nosala C;Dawson SC
本文就贾第鞭毛虫的功能生物学、编码和非编码基因、特性以及细胞和分子生物学的研究进展作一综述。我们认为目前对寄生虫的认识存在主要差距，并讨论了目前在体内和体外培养的最新技术。电子计算工具方面的进展，包括非编码RNA和基因组元件的建模，以及通过推断与模型生物体的同源性对编码基因的详细探索，提供了重要的初级洞察力。改进的蛋白质三维结构建模方法为蛋白质的功能以及与配体、其他蛋白质或前体药物的结合相互作用提供了新的见解，并为优先考虑蛋白质进行进一步研究和实验提供了大量机会。这些方法可以得到越来越多和高度可用的基于系统的方法的补充，这些方法现在应用于贾第虫，以基因组、转录组和蛋白质组学方法为首，但迅速纳入用于实时转录检测、染色质状态评估和直接测量大分子复合体的先进工具。近年来，直接询问和干扰基因功能的方法取得了重大进展，现在可以使用CRISPR干扰。这些方法，再加上蛋白质过度表达、荧光标记和体外和体内成像，将给该领域带来革命性的变化，并预示着一个激动人心的时期，在此期间，该领域可能最终实现贾第虫作为模式寄生虫和真核生物的长期潜力。
This review considers current advances in tools to investigate the functional biology of Giardia, it’s coding and non-coding genes, features and cellular and molecular biology. We consider major gaps in current knowledge of the parasite and discuss the present state-of-the-art in its in vivo and in vitro cultivation. Advances in in silico tools, including for the modelling non-coding RNAs and genomic elements, as well as detailed exploration of coding genes through inferred homology to model organisms, have provided significant, primary level insight. Improved methods to model the three-dimensional structure of proteins offer new insights into their function, and binding interactions with ligands, other proteins or precursor drugs, and offer substantial opportunities to prioritise proteins for further study and experimentation. These approaches can be supplemented by the growing and highly accessible arsenal of systems-based methods now being applied to Giardia, led by genomic, transcriptomic and proteomic methods, but rapidly incorporating advanced tools for detection of real-time transcription, evaluation of chromatin states and direct measurement of macromolecular complexes. Methods to directly interrogate and perturb gene function have made major leaps in recent years, with CRISPr-interference now available. These approaches, coupled with protein over-expression, fluorescent labelling and in vitro and in vivo imaging, are set to revolutionize the field and herald an exciting time during which the field may finally realise Giardia’s long proposed potential as a model parasite and eukaryote.
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