B. Dawes: Analyzing nucleic acids with optical tweezers

In this defense, I demonstrate how to analyze nucleic acids using optical tweezers. I begin by describing how to setup an optical tweezer. Specifically, I discuss how to setup an acousto-optic deflector to control the position of the optical traps as well as how to align the readout optics to detect bead motion at the trap centers. Next, I turn to analyzing data from nucleic acid transitions. I show that most implementations of hidden Markov modeling neglect the autocorrelation inherently present in optical tweezer data. I implement a hidden Markov model that accounts for such autocorrelation and show that it is able to label the folding states of nucleic acids more accurately. Finally, I apply this model to analyzing the structure and dynamics of the theophylline aptamer. In particular, I measure a stabilization of the folded structure by several $k_BT$ upon ligand binding. Understanding this stabilization is important for understanding the activity of the theophylline aptamer in synthetic biology applications.