Related Experiment Video
Updated: Jun 13, 2026
09:20
Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells
Published on: July 6, 2021
Counter-intuitive stochastic behavior of simple gene circuits with negative feedback
Tatiana T Marquez-Lago1, Jörg Stelling
1Department of Biosystems Science and Engineering and Swiss Institute of Bioinformatics, ETH Zurich, Basel, Switzerland. tatiana.marquez@bsse.ethz.ch
Biophysical Journal
|May 6, 2010
Summary
Negative feedback loops in gene regulation can surprisingly increase system noise. Model assumptions, like the quasi-steady-state assumption, significantly impact noise levels, challenging previous understandings of gene regulation homeostasis.
Area of Science:
- Systems Biology
- Molecular Biology
- Theoretical Biology
Background:
- Negative feedback loops are traditionally viewed as homeostatic mechanisms in gene regulation.
- Recent theoretical work suggests an counter-intuitive relationship between feedback strength and noise levels.
Purpose of the Study:
- To systematically analyze minimal gene regulation models with negative feedback.
- To investigate how model assumptions influence the relationship between feedback strength and noise.
Main Methods:
- Analysis of minimal gene regulatory models with transcriptional repressors.
- Inclusion and exclusion of quasi-steady-state assumptions.
- Examination of processes like RNA polymerase binding and repressor dimerization.
Main Results:
- Models with quasi-steady-state assumptions show noise buffering (RNA polymerase binding) or accentuation (repressor dimerization) with increased feedback.
- Simplified models underestimating transcription and translation impact noise.
- Models without quasi-steady-state assumptions consistently show increased noise with feedback.
Conclusions:
- Model assumptions and mathematical properties critically determine noise profiles in gene regulation.
- Previous conflicting findings on feedback and noise are explained by differing model simplifications.
- New approaches to characterizing noise in gene regulatory systems are proposed.
Related Concept Videos
01:07Cell Signaling Feedback Loops
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
01:18Positive and Negative Feedback Loops
Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis ("steady state"). Examples of these changes include regulation of the level of glucose or calcium in the blood or internal responses to external temperatures. Homeostasis requires maintaining an internal dynamic equilibrium:
01:18Negative and Positive Feedback
Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis ("steady state"). Examples of these changes include regulation of the level of glucose or calcium in the blood or internal responses to external temperatures. Homeostasis requires maintaining an internal dynamic equilibrium:
01:24Effects of feedback
Feedback in control systems plays a critical role in shaping various operational parameters, extending beyond simple error reduction to influence stability, bandwidth, gain, impedance, and sensitivity. Understanding these effects requires examining a basic feedback system characterized by defined input, output, error, and feedback signals.
Feedback significantly modifies the gain of a control system. The gain of a system without feedback is altered by a factor of one plus GH, where G represents...
Feedback significantly modifies the gain of a control system. The gain of a system without feedback is altered by a factor of one plus GH, where G represents...
01:23Root Loci for Positive-Feedback Systems
The Hartley oscillator is a positive feedback system that sustains oscillations by feeding the output back to the input in phase, thereby reinforcing the signal. Positive feedback systems can be viewed as negative feedback systems with inverted feedback signals. In these systems, the root locus encompasses all points on the s-plane where the angle of the system transfer function equals 360 degrees.
The construction rules for the root locus in positive feedback systems are similar to those in...
The construction rules for the root locus in positive feedback systems are similar to those in...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.