Fluorescent Sensors to Image RNA

University Of Pittsburgh, Pittsburgh PA

Investigators

Abstract

The Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation supports Professor Kazunori Koide of the University of Pittsburgh who proposes to chemically synthesize small molecule-based cell-permeable RNA sensors that fluoresce when bound to specific RNA. Chemical synthesis is concise and amenable to tuning sensitivity and specificity. Previously, it was thought that a library of RNA chemosensor candidates must be synthesized and screened against specific RNA. However, it is exceedingly difficult to rationally design specific RNA ligands and strenuous to chemically synthesize a library of small molecules. The significance of this proposed research is that one does not need to create RNA ligands to develop RNA chemosensors; rather, the proposed research will take advantage of well-established in vitro RNA selection as a means to engineer specific RNA-small molecule interaction with some help from synthetic organic chemistry. This reversed paradigm for RNA sensor development is highly innovative and will have significant impact on how others will design experiments to develop other RNA sensors. The biology of RNA in live cells is poorly understood due to the lack of probes. This research focuses on developing chemosensors that fluoresce only when bound to specific RNA. The approach is based on the combination of rational design and library-based discovery. The outcome of this study will have broad impact on bioimaging and the biology of DNA transcription. Research by Professor Koide could significantly impact chemistry, biology, the pharmaceutical industry, and the general public. This project will train students and postdoctoral fellows to become scientists who will be able to bridge the gap between chemistry and biology. Leaders in pharmaceutical and biotechnology companies require knowledge in both fields to invent drugs or diagnostic tools, for which this project will produce well-trained scientists. Students trained by this research project will understand synthetic, analytical, and spectroscopic chemistry as well as biology, and will be able to be engaged in multidisciplinary efforts that are at the forefront of science.