CAREER: Simultaneous Single-Molecule Manipulation and Visualization for Study of ATP Coupling to Base Pair Unzipping

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With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Wei Cheng at University of Michigan and his group will develop an ultrasensitive technique that allows manipulation and visualization of a biochemical reaction, one molecule at a time. They will use this technique to study how ATP is consumed for base pair unzipping in a helicase-catalyzed reaction. 2% of the eukaryotic genome encodes helicase proteins. These proteins are ubiquitous and use ATP to unzip DNA or RNA so that genetic information is accessible for further processing. However, the mechanism of how these enzymes use ATP for bp unzipping remains poorly understood. This project focuses on the development of a single-molecule technique to simultaneously manipulate and visualize the reaction of hepatitis C virus NS3 protein, a model helicase. The success of this technique can lead to fundamental knowledge in our understanding of helicase mechanism, and allows quantitative measurement of a broad range of biochemical reactions in exquisite detail.The broader impacts of this project involve research and teaching activities that aim to emphasize the importance of technical innovation in advancement of science, particularly to students with interests in biochemistry and biophysics. Professor Cheng proposes to teach biochemistry classes with emphasis on technical innovation that enabled important scientific discoveries. Moreover, he plans to establish an annual single-molecule showcase in his lab, which will be open to local high school and college students. Through simple demonstration experiments and hands-on experience, he hopes to inspire the students' interest in basic science.