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)
Sargis Karapetyan successfully defended his dissertation on “Design principles and coupling of biological oscillators”. Congratulations! Sargis is now a Physics Ph.D.
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).
Selcan Aydin measured GAL1 gene expression at low galactose levels in single yeasts using timelapse luminescence microscope. Her data shows that the graded increase in GAL1 induction at the population level reflects a heterogeneous induction lag at the single cell level (click here to see movie). This work illustrates the power of single cell analysis using timelapse luminescence microscopy; see Mazo-Vargas et al, MBoC 2014. This was a quick collaboration with the Pascual-Ahuir and Proft labs.
Rienzo A, Poveda-Huertes D, Aydin S, Buchler NE, Pascual-Ahuir A, Proft M. Different mechanisms confer gradual control and memory at nutrient- and stress-regulated genes in yeast. Mol. Cell. Biol. 2015; 35: 3669-83.