Studying gene expression in model microbial organisms.

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控的，从而从mRNA分子合成蛋白质。蛋白质合成，也被称为翻译，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。翻译调控是在细胞转化、应激和细胞凋亡等不同生理条件下调节多种mRNAs的表达。翻译中的异常与普遍存在的人类疾病有关，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讯。为此，我们分别使用了模式原核和真核生物大肠杆菌和面包师酵母，酿酒酵母。在即将到来的授权期，我们建议在以前工作的基础上，研究真核细胞翻译起始区如何在原核生物中发挥作用。我们还有兴趣研究mRNA结合蛋白Dom34对非标准(不依赖于mRNA帽的)真核细胞翻译启动的影响。原核生物和真核生物翻译过程中最显著的区别之一就是mRNA的识别和结合。最近的一项研究表明，原核和真核细胞的mRNA识别和结合可能并不像之前认为的那样明显。作者发现，非标准的真核生物内部核糖体进入位点(IRES)可以在原核生物中介导选择性翻译起始。我们计划以大肠杆菌为模型系统，研究该真核信号介导的原核翻译启动机制。这是一个重要的进化论问题，可以显著影响我们目前对该领域的机械论水平的理解。此外，我们之前已经证明，mRNA结合蛋白Dom34可以影响某些IRESS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因子的活性。将Dom34确立为可以不分青红皂白发挥作用的IRESS的新调节器将是一个非常有趣的发现，因为人们普遍认为，不同的IRESS需要不同的调节器。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识别影响原核生物和真核生物中某些IRES介导的翻译的因素。

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.