Lab Overview: How can we use mechanical forces in DNA to control gene expression?
We study how mechanical forces in DNA change gene expression and ultimately the fate of living cells.
The genome of a cell is twisted, double-helical DNA. The presence of twist in one location has direct consequences when displaced by transcription or replication.
Research Theme: Transcription-Induced Supercoiling
When an RNA polymerase transcribes a gene of interest, the twist is displaced into the surrounding parts of the DNA. The rate of this displacement and kinetics of migrating twist impact the transcriptional rates of neighboring genes.
We seek to develop new experimental methods to visualize the displacement and kinetics of migrating twist and their concomitant impact on neighboring gene expression. We seek to develop accurate biophysical models to describe the spatiotemporal evolution of DNA twist, writhe, transcription, and replication.
Research Theme: Supercoiling and Cell Fate
When DNA twist is allowed to dissipate and impact neighboring genes, there can be antagonistic, winner-takes-all, asymmetric, symmetric, or mutually synergistic effects. The precise biophysical constraints that govern the balance of whether supercoiling-mediated feedback is antagonistic or mutually synergistic has important consequences on how one cell expresses versus another in a population. In 2016, we first observed that simply rearranging the composition of two independent genes in bacteria, to change the supercoiling states of the surrounding DNA, led to stark differences in how cells expressed their genes.
Figure: Time-lapse fluorescence microscopy reveals two genes generate distinct phenotypes in E. coli MG1655K12 bacteria when gene order and direction are shuffled on circular DNA. The top, middle, and bottom row show what happens when genes are arranged in convergent, divergent, and tandem orientation, respectively.
Research Theme: Supercoiling and Programmed Topological Barriers
The propagation of DNA twist can be controlled or modulated by the presence of topological barriers. Large proteins, DNA looping proteins, and even the very act of neighboring transcriptional elements can prevent the migration of DNA twist. We are interested in developing new genetic elements and sequence-programmable components in living cells to program dynamic regulation of DNA twist.
Lab News
June 2026: Congratulations to this year’s BCL graduates: Harris Clark (ChemE), Jiayi Wu (Biochemistry), Dr. Charles Johnson (MechE, PhD), Kevin Chang (Math,BS), Paige Nickerson (Biology), Annie Nguyen (MechE, MS), Daniel Park (MechE, MS).
We wish the best of luck to Harris, Kevin, Jiayi, Annie, and Paige as they begin their next chapter at Princeton, Georgia Tech, Stanford, Zymogen, and medical school, respectively.
May 2026: Congratulations to Dr. Charles Johnson on successfully defending his PhD dissertation! During his PhD, Charles researched the mathematical reasons why deep neural networks are so effective at learning operator theoretic models from data. You can read more about Charles’ work here.
Feb 2026: Congratulations to Dr. Taishi Kotsuka, who will be starting as a new faculty at the Tokyo University of Agriculture and Technology in the Department of Mechanical System Engineering. Taishi worked on multiple publications in our group, as a Postdoctoral Fellow of the Japanese Society for the Promotion of Science. He developed a way to control peak sharpness in stochastic gene networks a novel genetic controller and a new framework for model reduction of multi-cellular sender-receiver networks. Congratulations Professor Kotsuka!
Nov 2025: Dr. Lili Yang and Dr. Yanran Wang have used single-molecule imaging to discover that multiple RNA polymerases on DNA traps supercoiling and causes the formation of plectonemes! The preprint of their work is here.
On the right is a figure from their work showing a 20 kb DNA strand under active transcription, forming two plectonemes, in direct response to transcription of 3 synthetic genes.
Many thanks to Omar Saleh, Terence Strick, Sam Meyer, Jean-Yves Bouet, Sarah Harris, Craig Beckham, Estelle Brandon, and Ivan Junier for all your useful feedback and comments on our work!
