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CRISPR之父张锋2017年开年综述:生与死的选择

2016-12-31 MedSci MedSci原创

Broad研究员的CRISPR技术先锋张锋,与美国国立健康研究院Eugene V. Koonin研究员合作发表了一篇综述。在文中他们指出,CRISPR-Cas的盛行主要是因为其在基因组编辑与调控中可以作为新一代的研究工具,但是CRISPR-Cas系统本身也令人着迷,尤其是作为一种独特的免疫系统机制,可以说,CRISPR-Cas功能中最绚烂的部分就是它是唯一一种已知的,携带可遗传基因组记忆的获得性免

Broad研究员的CRISPR技术先锋张锋,与美国国立健康研究院Eugene V. Koonin研究员合作发表了一篇综述。在文中他们指出,CRISPR-Cas的盛行主要是因为其在基因组编辑与调控中可以作为新一代的研究工具,但是CRISPR-Cas系统本身也令人着迷,尤其是作为一种独特的免疫系统机制,可以说,CRISPR-Cas功能中最绚烂的部分就是它是唯一一种已知的,携带可遗传基因组记忆的获得性免疫系统,即拉马克理论中获得性性状遗传机制。

几乎所有的细胞生命形式都有多种抗击寄生生物的防御系统,比如改变自身遗传组成,阻挡寄生生物入侵,天然免疫系统,获得性免疫系统,还有就是程序性死亡(programmed cell death,PCD)。CRISPR页方式一种细菌的防御系统,这一全称为规律成簇的间隔短回文重复(Clustered Regularly Interspaced Short Palindromic Repeats)的结构与内切酶Cas9一道,帮助细菌组成防御系统对抗外来侵略者,也就是说CRISPR-Cas9能够在引导RNA的指引下,靶标并切割入侵者的遗传物质。

近期Broad研究员的CRISPR技术先锋张锋,与美国国立健康研究院Eugene V. Koonin研究员合作发表了一篇综述:Coupling immunity and programmed cell suicide in prokaryotes: Life-or-death choices。在文中他们指出,CRISPR-Cas的盛行主要是因为其在基因组编辑与调控中可以作为新一代的研究工具,但是CRISPR-Cas系统本身也令人着迷,尤其是作为一种独特的免疫系统机制,可以说,CRISPR-Cas功能中最绚烂的部分就是它是唯一一种已知的,携带可遗传基因组记忆的获得性免疫系统,即拉马克理论中获得性性状遗传机制。

同时CRISPR-Cas系统的发现也刺激了原核生物防御系统的研究,在这个过程中,免疫力与程序性死亡之间千丝万缕的关系变得更为明确了,从而这两种防御系统之间的功能偶联关系理论也逐渐形成。这篇综述就主要探讨了这两者之间的关联,并从目前的研究发现出发,介绍了一些防御系统,免疫力与程序性死亡的有限融合。

2015年,张锋研究组在Molecular Cell杂志上公布了新的CRISPR-Cas基因组编辑系统(详情),他们采用了一种新生物信息学方法发现了被命名为C2c1、C2c2和C2c3的新蛋白,这些蛋白系统具有自身一些独特的性质,并在之后的研究中鉴别并确定了能够靶向和降解RNA的一种RNA引导酶——C2c2的功能特征(详情)。

研究组成员将这些新系统定义为第6类CRISPR-Cas 系统(VI CRISPR-Cas systems),这一系统具有双重免疫力-自杀功能,比如说C2c2这一种第一个确定只靶向RNA的自然CRISPR系统,能帮助保护细菌对抗了病毒感染,研究人员指出C2c2揭示出了细菌利用来防御病毒的一个全新生物机制,这也是研究防御系统融合的一个新材料。

目前CRISPR-Cas系统可分为两个不同的种类,每种包含三大类型和多个亚型。结合生物化学与分子遗传学大大推动了揭示不同CRISPR-Cas类型许多独特的特征。此外,结构分析和单分子研究进一步增进了我们对CRISPR-Cas功能分子基础的认识。但是我们对CRISPR-Cas系统的认识还有许多问题有待揭示,比如对于近期发现并确定了新CRISPR-Cas类型的特征表明,以我们当前的知识来预测亲缘关系遥远的CRISPR-Cas变体的功能细节能力还相对有限。因此,需要彻底地剖析新发现的CRISPR-Cas系统认识它们的生物学作用,揭示它们的分子机制,利用它们的潜能来开发生物技术。

原始出处:

Koonin EV, Zhang F. Coupling immunity and programmed cell suicide in prokaryotes: Life-or-death choices. Bioessays. 2017 Jan;39(1):1-9. doi: 10.1002/bies.201600186.

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    2017-02-09 依way

    收藏起来备用

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    2017-01-02 yuandd
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    2017-01-01 yafeiliutjh

    要学习的

    0

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    2017-01-01 inter158

    学习这文章了

    0

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    2017-01-01 半夏微凉

    学习了!继续努力!

    0

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    2017-01-01 wolixiang2012

    很厉害的文章

    0

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    2016-12-31 知难而进

    学习了!!!!!!

    0

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    2016-12-31 九九消寒

    这就是活着

    0

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    2016-12-31 sucess1314

    大家都很好的结局的结局是教师节

    0

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