Specific Interactions of the Ribosome with the Nascent Peptide

智慧价值核糖体是一台负责合成蛋白质的细胞分子机器。人们直到最近才认识到，核糖体不仅可以组装新的蛋白质，还可以检查它制造的蛋白质的结构。核糖体可以识别新合成蛋白质结构中的特定信号，并对这些结构中编码的特定信息做出反应。这种核糖体反应被怀疑控制了许多基因的表达并优化了蛋白质的生产。然而，蛋白质检测的机制还不是很清楚，也不知道受这一机制调控的细胞基因的谱。该项目的主要目标是识别受蛋白质检测机制控制的细菌基因，并了解这种机制在分子水平上是如何运作的。将研究核糖体和新生蛋白质之间的通讯原理，并探索影响这些通讯的新方法。尖端基因组学和蛋白质组学技术将用于检查核糖体如何读取单个细胞基因的遗传信息，并确定核糖体暂停的位置。这样的位置通常表明核糖体从新合成的蛋白质中接收到了“减慢”信号。核糖体暂停发生的基因之间的结构相似性将被识别，并将使用新的生化技术探索信号识别和核糖体反应的分子机制。广泛影响这项研究的结果可能会显著改变我们对蛋白质是如何合成和基因是如何调控的理解。这项研究中可能解开的原理可能不仅适用于细菌，也适用于其他细胞和有机体。新获得的知识可以造福科学，因为它可能对优化细菌中有用蛋白质的生产具有重要的生物技术影响。这项研究将对教育和向公众推广科学知识产生直接影响。研究结果将立即用于药剂学专业人员和研究生的课程。延续以往的做法，该项目将用于吸引研究生、本科生和高中生开展相关的基础研究。该研究的部分内容将作为科学项目提供给芝加哥地区的高中生。参与研究的人员将在芝加哥市中心的学校参加与科学有关的活动，特别是将努力集中在那些科学方面代表不足的少数族裔学生比例较高的学校。将招收国际学生和实习生协助这项研究，这将有助于向其他国家传播科学知识。此外，它还将支持爱沙尼亚正在进行的国际合作。该项目是与国际科学和工程办公室联合资助的。

Intellectual MeritThe ribosome is a cellular molecular machine that is responsible for synthesis of proteins. It has been recognized only recently that the ribosome not only assembles new proteins, but can also inspect the structure of the protein it makes. The ribosome can recognize specific signals in the structure of the newly synthesized protein and it can respond to certain messages encoded in these structures. Such ribosomal response is suspected to control expression of many genes and to optimize protein production. However, the mechanism of the protein inspection is not well understood, nor is the spectrum of cellular genes regulated by this mechanism known. The main goal of the project is to identify bacterial genes that are controlled by the mechanism of the protein inspection and to understand how this mechanism operates at the molecular level. The principles of communication between the ribosome and the nascent protein will be investigated and new ways to affect these communications will be explored. Cutting-edge genomics and proteomics techniques will be used to inspect how the ribosomes read the genetic information of individual cellular genes and to identify the sites of the ribosome pausing. Such sites usually indicate that the ribosome received a "slow down" signal from the newly synthesized protein. The structural similarities between the genes at which ribosome pausing occurs will be identified and molecular mechanisms of signal recognition and ribosomal response will be explored using novel biochemical techniques.Broader ImpactThe results of the study may significantly change our understanding of how proteins are being made and how genes are regulated. The principles that might be unraveled in this investigation likely apply not only to bacteria but also to other cells and organisms. The newly acquired knowledge can benefit science as it may have important biotechnological implications for optimizing production of useful proteins in bacteria. The research will have a direct impact on education and advancing scientific knowledge to the public. The results of the study will be immediately used in the curriculum of the Pharmacy professional and graduate students. Continuing the previous practices, the project will be used to attract graduate, undergraduate and high school students to carry out relevant fundamental research.Some parts of the study will be offered as science projects for the high-school students from Chicago area. The personnel involved in the study will participate in science-related activities in the inner-city schools in Chicago, especially focusing the effort on schools with a high proportion of students from ethnic groups underrepresented in science. International students and interns will be enrolled to assist with the study which will help to disseminate scientific knowledge to other nations. In addition, it will support an ongoing international collaboration in Estonia. Project is supported jointly with the Office of International Science and Engineering.