PTXL Research Group

 

Goal: Our goal is to understand the fundamental principles that governing the folding of RNA and to protein-RNA interactions.

Overview: Folding of an RNA molecule can be viewed as a biased diffusion over its folding energy landscape. Such landscape is populated with different energetic states, similar to “hills” and “valleys” on a geographic map. We survey the folding energy landscape by following folding trajectories of individual molecule. Relative levels of energetic states are reflected by folding rates as high energy barrier slows folding. Also, a molecule is more likely to take an “easy” route to fold than to follow a “difficult” one. We are particularly interested in three areas. (1) Force induced misfolding; (2) Formation of RNA kissing complexes, a type of tertiary structures formed between loops of two hairpins; (3) Ligand and protein binding to RNA structures.

Approach: We use a device called optical tweezers to apply pico-Newton (10-12 Newton) force to single RNA molecules. As an RNA molecule folds and unfolds, changes in the extension of the molecule, measured with nanometer precision, reflect structural transitions in real time. Parallelly, we use biochemical and spectroscopic methods to study RNA folding at ensemble. We also employ statistical mechanical modeling to interpret experimental results both in-house and through collaboration.

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