Studying gene expression in model microbial organisms.

研究模型微生物中的基因表达。

• 批准号: RGPIN-2019-06143
• 负责人: Golshani, Ashkan
• 金额: $ 3.06万
• 依托单位: Carleton University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714817
• 关键词: Studying; gene; expression; model; microbial

The overall goal of the research program in my laboratory is to achieve a better understanding of how gene expression is regulated, resulting in the synthesis of proteins from mRNA molecules. Protein synthesis, also known as translation, is an essential requirement for the survival of a cell, and the cellular machinery responsible for translation is highly conserved throughout the course of evolution. Translation control is used to regulate the expression of a variety of mRNAs under different physiological conditions such as cell transformation, stress, and apoptosis. Abnormalities in translation have been linked to pervasive human conditions such as cancer and diabetes, among others. My laboratory is particularly interested in identification of mechanisms and novel factors that affect protein synthesis, as well as the regulations and cross-communications between different cellular processes that govern protein synthesis. For this, we use the model prokaryotic and eukaryotic organisms Escherichia coli, and the baker's yeast, Saccharomyces cerevisiae, respectively. In the upcoming grant period, we propose to build on our previous work and to investigate how a eukaryotic translation initiation region can function in prokaryotes. We are also interested in studying the influence of an mRNA binding protein Dom34 on non-standard (mRNA cap-independent) eukaryotic translation initiation. mRNA recognition and binding to mediate translation initiation is one of the most notable differences between prokaryotic and eukaryotic translations. In a recent study, it was illustrated that prokaryotic and eukaryotic mRNA recognition and binding may not be as distinct as previously thought. The authors showed that a non-standard eukaryotic Internal Ribosome Entry Site (IRES) can mediate alternative translation initiation in prokaryotes. Using E. coli as a model system, we plan to study the mechanism of prokaryotic translation initiation mediated by this eukaryotic signal. This is an important evolutionary question and can significantly impact our current understanding of the field at a mechanistic level. In addition, we have previously shown that the mRNA binding protein Dom34 can influence the activity of certain IRESs. We also plan to further investigate the activity of Dom34 as a general regulator of cap-independent protein synthesis in yeast. Establishing Dom34 as a novel regulator of IRESs that may function indiscriminately will be a very interesting finding as it is generally accepted that different IRESs require different regulators. Our expertise in large scale genome-wide studies and approaches will further enable us to identify factors that influence certain IRES mediated translations in both prokaryotes and eukaryotes.

我实验室研究项目的总体目标是更好地了解基因表达是如何调节的，从而从mRNA分子合成蛋白质。蛋白质合成，也称为翻译，是细胞生存的基本要求，负责翻译的细胞机制在整个进化过程中高度保守。翻译控制用于在不同的生理条件如细胞转化、应激和凋亡下调节多种mRNA的表达。翻译的缺失与人类普遍存在的疾病有关，如癌症和糖尿病等。我的实验室特别感兴趣的是识别影响蛋白质合成的机制和新因素，以及管理蛋白质合成的不同细胞过程之间的调节和交叉通信。为此，我们分别使用原核和真核生物大肠杆菌和面包酵母酿酒酵母作为模型。在即将到来的资助期间，我们建议建立在我们以前的工作，并调查如何真核生物的翻译起始区可以在原核生物中发挥作用。我们也有兴趣研究的影响，mRNA结合蛋白Dom34非标准（mRNA帽独立）真核生物翻译起始。mRNA识别和结合介导翻译起始是原核和真核翻译之间最显著的差异之一。在最近的一项研究中，表明原核和真核mRNA的识别和结合可能不像以前认为的那样不同。作者表明，非标准的真核内部核糖体进入位点（IRES）可以介导原核生物中的替代翻译起始。使用大肠coli作为模型系统，我们计划研究该真核信号介导的原核翻译起始机制。这是一个重要的进化问题，可以显著影响我们目前在机械水平上对该领域的理解。此外，我们以前已经表明，mRNA结合蛋白Dom34可以影响某些IRES的活性。我们还计划进一步研究Dom34作为酵母中帽非依赖性蛋白质合成的一般调节剂的活性。将Dom34确定为可不加区别地发挥作用的IRES的新型调节剂将是一个非常有趣的发现，因为人们普遍认为不同的IRES需要不同的调节剂。我们在大规模全基因组研究和方法方面的专业知识将进一步使我们能够确定影响原核生物和真核生物中某些IRES介导的翻译的因素。