Studying gene expression in model microbial organisms.

我实验室研究项目的总体目标是更好地理解基因表达是如何被调节的，从而导致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是高度保守的。翻译调控用于调控多种mrna在细胞转化、应激、凋亡等不同生理条件下的表达。翻译异常与癌症和糖尿病等普遍的人类疾病有关。我的实验室特别感兴趣的是确定影响蛋白质合成的机制和新因素，以及控制蛋白质合成的不同细胞过程之间的调节和交叉通讯。为此，我们分别使用模型原核生物大肠杆菌和真核生物大肠杆菌，以及面包酵母，酿酒酵母。在即将到来的授权期内，我们建议在我们之前的工作的基础上，研究真核生物翻译起始区如何在原核生物中发挥作用。我们也有兴趣研究mRNA结合蛋白Dom34对非标准（mRNA帽独立）真核翻译起始的影响。mRNA识别和结合介导翻译起始是原核生物和真核生物翻译之间最显著的区别之一。最近的一项研究表明，原核生物和真核生物的mRNA识别和结合可能并不像以前认为的那样不同。作者发现一个非标准的真核内部核糖体进入位点（IRES）可以介导原核生物的替代翻译起始。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起始机制。这是一个重要的进化问题，可以在机制层面上显著影响我们目前对该领域的理解。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作为酵母中帽无关蛋白合成的一般调节因子的活性。将Dom34作为IRESs的一种新的调节因子，可以不加区分地发挥作用，这将是一个非常有趣的发现，因为人们普遍认为不同的IRESs需要不同的调节因子。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.