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Related Experiment Video

Updated: May 14, 2026

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

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Published on: July 6, 2021

Small-number effects: a third stable state in a genetic bistable toggle switch.

Rui Ma¹, Jichao Wang, Zhonghuai Hou

¹School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, Anhui, China.

Physical Review Letters

|February 2, 2013

Summary

Researchers explored a genetic toggle switch, discovering a new stable state with low gene expression. This state, unexpected by theory, arises from the system's small, fluctuating nature.

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Area of Science:

Synthetic biology
Genetic circuit engineering
Biophysics

Background:

Genetic toggle switches are fundamental synthetic gene circuits.
Understanding their stable states is crucial for circuit design and function.
Existing models often assume deterministic, large-scale systems.

Purpose of the Study:

To experimentally and theoretically investigate a genetic toggle switch.
To identify and characterize all possible kinetic stable states.
To understand the influence of system size and stochasticity on circuit behavior.

Main Methods:

Experimental implementation of a genetic toggle switch circuit.
Theoretical modeling using differential equations for deterministic dynamics.
Exact stochastic simulations to capture system fluctuations.
Comparison of experimental data with modeling predictions.

Main Results:

Discovery of an additional, kinetically stable state with very low gene expression.
Experimental validation of this low-expression state, contradicting deterministic predictions.
Demonstration that this state can stably coexist with other known states.
Attribution of the novel phenomenon to the discrete and fluctuating nature of the small system.

Conclusions:

Small genetic circuits exhibit emergent behaviors not predicted by deterministic models.
Stochasticity and discreteness are critical factors in the stability and coexistence of states in genetic switches.
Findings necessitate revised theoretical frameworks for small-scale biological systems.