Research Interests

RNA has dual functions. It can both encode genetic information and work as a biocatalyst (enzyme). The discovery of RNA serving as both “chicken” and “egg” provides an important clue to the evolution of biological life.

RNA structure governs function inside the cell. Therefore, understanding the biological function of RNA requires an accurate knowledge of the secondary and tertiary structural features of RNA. Local nucleotide flexibility of an RNA can be monitored by treating RNA with 2’-hydroxyl-reactive electrophiles such as N-methylisatoic anhydride, which selectively and covalently modifies flexible nucleotides at the 2’-ribose position.

The detection of the modified RNA nucleotides is based on primer extension by reverse transcriptase: Modified nucleotides stop the cDNA synthesis. Slab gel electrophoresis (SGE) with its well-established reliability has long been used to size the synthesized cDNA fragments. However, SGE suffers from several limitations including the low speed of electrophoresis and lack of automation. Microchip-based gel electrophoresis is a promising alternative to the conventional SGE system due to its shorter analysis time, less sample consumption, higher sensitivity, and automatic operation. Wang’s research focuses on the development of RNA structural analysis approach in microfabricated devices. Currently Wang is working on four projects.

Project 1: Analysis of RNA structure in microdevices fabricated by different materials. Our interest is in using glass and polymer microchip-based gel electrophoresis system to separate and detect the synthesized cDNA fragments. Among numerous polymer materials, polydimethysiloxane (PDMS) and polymethylmethacrylate (PMMA) are the first choices due to their excellent surface properties and the ease of fabrication. PDMS microchips are fabricated by micro-molding method whereas PMMA microdevices are prepared by hot embossing. Besides the single-channel microchips, we are interested in fabricating polymer microdevices with multi-lane capacity and micro total analysis systems to perform RNA preparation, chemical modification, cDNA synthesis, separation and detection on one microchip.

Project 2: Application of the microchip-based RNA structural analyzing technology. In this project, we focus on investigating the specific RNA-therapeutic drug binding and RNA-protein interactions via elucidating the RNA folding schemes. RNA structural analyzing technology is coupled with NMR, X-ray crystallographic study and atomic force microscopy (AFM) to understand the specific ways that RNA fold.

Project 3: Mapping RNA-RNA and RNA-peptide interaction forces using chemical force titrations. In this project, we are interested in quantifying the chemical forces exist between RNA and RNA, and between RNA and peptides under different solution environments. Chemical force microscopy (CFM) is a variation of traditional AFM in which chemical specificity is added by attaching distinct functional groups/molecules to an AFM probe. The CFM can then be used to characterize adhesive interactions between the probe tips and substrates as a function of solution pH or of the composition of the solvent used.

Project 4: Analysis of RNA structure by single molecule approaches.