Research: P.T.X. Li

Our goal is to understand the fundamental principles that govern the folding of RNA and to apply such knowledge to engineer macromolecular assembly. Folding of an RNA molecule can be viewed as a biased diffusion over its folding energy landscape. Such energy landscape can be characterized by following molecular trajectories of individual molecules. Using optical tweezers technique, we stretch and relax single RNA molecules. This rubber-band-like experiment allows us to apply picoNewton (10 -7 gram) force to unfold the RNA structure and measure changes in the molecular extension with nanometer precision. Currently, we focus on three areas: (1) Force induced misfolding. By changing force in different ways, we can induce RNA molecules to fall into kinetic traps and then rescue them into the native structure. This method provides a unique way to survey the topography of the folding energy landscape. (2) RNA kissing complex, a tertiary structure formed between loops of two hairpins. By studying the formation and stability of such structures under mechanical tension, we measure the strength of tertiary interactions and the constraints of their formation. (3) Detecting ligand and protein binding to RNA structures by optical tweezers. We have developed a new method to pinpoint structural domains that bind to ligand or protein. Using this approach, we are developing new type of biosensors and drug screening strategy.