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在Trypanosoma brucei中对定数感应信号通路的全基因组剖析

Binny M Mony¹, Paula MacGregor¹, Alasdair Ivens¹

¹Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, EH9 3JT, United Kingdom.

|December 17, 2013

概括

研究人员确定了控制Trypanosoma brucei分化成传染性形式的关键信号通路. 这一发现为非洲三虫病提供了新的治疗点,三虫病是撒哈拉以南非洲的一个重要疾病.

科学领域:

寄生虫学的寄生虫学
分子生物学分子生物学
细胞信号传递细胞信号传递

背景情况:

在撒哈拉以南非洲,Trypanosoma brucei会引起人类和牲畜的疾病.
寄生虫分化为"瘦"和""的形式对于疾病传播至关重要.
"的诱导因子" (SIF) 和它的信号通路在很大程度上仍然没有特征.

研究的目的:

为了确定参与Trypanosoma brucei形的信号组件.
阐明调节密度依赖差异化的细胞内途径.
为了发现潜在的治疗点对非洲试虫病.

主要方法:

全基因组RNA干扰 (RNAi) 图书馆屏幕在实验室适应的三子体中.
选择对cAMP和AMP类似物无反应的寄生虫,以确定信号缺陷.
基于Ion Torrent的RNAi目标测序以识别涉及的基因.
在自然形成树的寄生虫中确定基因的验证.

主要成果:

鉴定了参与精氨酸代谢,信号转导 (激酶,酸酶) 和基因表达调节的基因.
在体内确认了这些基因在密度感应中的作用.
证明RNA结合蛋白RBP7对于定数感应至关重要,并且在过度表达时促进茎的形成.

结论:

试管体中的定数感知与真核生物静止路径有相似之处.
已识别的信号组件代表了新疗法的潜在目标.
干扰定数感应可以提供一种新的策略来打击非洲三虫病.

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