Mitch worked on synthetic biology as an independent research project for several years. The goal was to design a toggle switch that used a basic leucine zipper (C/EBPa) and a dominant-negative (3HF). His results were submitted as a honor’s thesis and he graduated with distinction in Biology. Congratulations!
In theory, the unbinding rates of activators and repressors from DNA are presumed to be faster than gene expression. In practice, this assumption is not always true. Sargis Karapeytan analyzed two synthetic oscillators (activation-titration and repressor-titration) to understand the key parameters that are important for oscillations and for overcoming the molecular noise that arises from slow DNA unbinding. Counter-intuitively, our biophysical modeling and stochastic simulations showed that slow values of DNA unbinding rate stabilized the oscillators. We also show that multiple binding sites increase the robustness of oscillations due to the buffering of DNA unbinding events. This work demonstrates how the number of DNA binding sites and slow unbinding kinetics, which are often omitted in biophysical models of gene circuits, have a significant impact on the dynamics of synthetic oscillators.
Karapetyan S, Buchler NE. Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators. Phys. Rev. E 92: 062712 (2015)
His committee was Joshua Socolar (Physics), Gleb Finkelstein (Physics), Berndt Mueller (Physics), Xinnian Dong (Biology), and Nicolas Buchler (Physics & Biology). Here’s a picture of Sargis with Armenian brandy (after the thesis).