How do mechanical forces in DNA shape gene dynamics and cell fate?
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.
Lab Overview
We study how variation in mechanical forces in DNA and genetic architecture change gene expression and the fate of living cells. We seek to understand how physical properties of DNA, e.g., supercoiling, writhing, and DNA compaction, regulate gene expression, store information, and control the fate of single cells and populations of cells. We are also interested in the principles of design for engineering synthetic DNA, both small-scale (synthetic genetic circuits) and large-scale (synthetic genomes).
We employ a broad range of methods to study these questions, drawing from methods in DNA biophysics, in vivo synthetic biology, in vitro cell-free lysate methods, multi-omics science, systems biology, microfluidics, control theory, dynamical systems theory, and machine learning.
Lab News
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!
June 2025: Jiayi (Judy) Wu has developed a multiple-layered feedforward genetic circuit that can generate approximate square waveforms in cells. She presented her work at a poster session at the 2025 SEED conference. Congratulations Jiayi!
The preprint to her paper can be found here.
May 2025: Congratulations to Charles Johnson, who leads a publication in the Journal of Nonlinear Science, cracking the puzzle as to why deep neural networks effectively learn liftings and higher-order transformations for Koopman operator models. Charles discovered two classes of nonlinear functions that define an algebra for Koopman observables that satisfy the Koopman equation, both in the exact and numerically approximating sense.
Jan 2025: Congratulations to our PhD student Jamiree Harrison on a compelling and highly attended PhD defense. His dissertation was titled “Parameter-varying models for hybrid promoters in bacterial genetic circuits.” Dr. Harrison will be starting a new position at Apple in August! Congratulations Jamiree!
