Specific Interactions of the Ribosome with the Nascent Peptide

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

Intellectual Merit The 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 Impact The 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.