CAREER: Single-molecule Studies of RNA and Ribonucleoprotein Enzymes

Harvard University, Cambridge MA

Investigators

Abstract

The scientific component of this CAREER project focuses on single-molecule explorations of RNA and ribonucleoproteins (RNP) enzymes. The work involves the study of the folding/assembly dynamics of RNA and RNP enzymes at the single-molecule level using fluorescence spectroscopy and will explore the correlation between the structural dynamics and function. Specifically, the work will entail 1) a study of the structural dynamics of small RNA enzymes including the hairpin ribozyme to reveal general principles of RNA structural formation and strong correlations between structural dynamics and catalytic activity; 2) characterization of the folding dynamics and energy landscape of a large multi-domain RNA, the group I intron BI5, to explore the capabilities and limitations of RNA as functional enzymes; 3) elucidation of the structural dynamics of an RNP enzyme, BI5/CBP2, to reveal the effect of proteins on the structural dynamics and functional capabilities of RNA; and, finally, 4) as a long-term goal that will be initiated in this program, exploration of the assembly dynamics of complex RNP particles such as the signal recognition particle. The project provides undergraduate, graduate, and postgraduate students a solid and advanced education in the interdisciplinary area between physics, chemistry and biology. The methodologies developed and knowledge derived from the work are being incorporated into a new interdisciplinary course that the PI is developing, Molecular Biophysics and Biophysical Chemistry. The course material will be organized into a textbook, which is greatly needed in this new and growing scientific area. This project is jointly funded by the Physics Division in the Mathematical and Physical Sciences Directorate and by the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.