ChBE Seminar Series: Chase Beisel
Tuesday, April 13, 2010
11:00 a.m.-12:15 p.m.
Room 2110 Chemical and Nuclear Eng. Bldg.
Professor F. Joseph Schork
Understanding and exploiting the regulatory potential of RNA
Presented by Dr. Chase Beisel, Ph.D.
RTA Post-Doctoral Fellow
Cell Biology and Metabolism Program, NICHD NIH
RNA is a fundamental building block of life endowed with unique molecular properties. These include the ability of an RNA strand to identify its sequence complement through base pairing interactions and fold into complex structures capable of specific binding and catalysis. Nature has repeatedly exploited these properties to control cellular processes. With the increasing availability of genomic sequences and advanced identification tools, the number and types of regulatory RNAs present in nature are rapidly expanding. As an engineer, I am interested in capitalizing on this emerging knowledge to construct synthetic regulatory RNAs tailored to applications in biotechnology and medicine.
In this talk I will present two general approaches to design regulatory RNAs. Under the first approach, the inherent molecular properties of RNA are integrated through rational design. Specifically, I will discuss how ligand-binding RNAs called aptamers and activators of RNA interference can be combined to yield conditional gene silencing in mammalian cells. Importantly, the designs I will discuss display modularity and tunability - critical properties when tailoring regulatory molecules to selected applications.
The second approach first asks how nature has utilized RNA as a regulatory tool to focus on designs already validated through evolution. While the number of existing natural examples serves as a basis for the design of synthetic RNAs, gaps in current knowledge prevent the development of fully functional analogues. To fill this gap, I am currently investigating a class of regulatory RNAs that relay stress signals in bacteria. I will show how these RNAs act in concert with protein regulators to coordinate the cellular response to stress, suggesting the utility of RNA in the context of regulatory networks. Overall, RNA design holds tremendous promise in the construction of biological systems and exploiting the regulatory potential of RNA would greatly benefit from combining human ingenuity and the success stories of natural evolution.