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Measurement of bistability in a multidimensional parameter space.
Vincent Jaquet1, Chieh Hsu2, Attila Becskei1
1Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland. attila.becskei@unibas.ch.
Integrative Biology : Quantitative Biosciences From Nano to Macro
|January 31, 2017
Summary
This study reveals how to reliably measure bistability in gene circuits. A novel threshold method helps determine the robustness of cellular states, crucial for cell fate decisions and diversity.
Area of Science:
- Systems Biology
- Synthetic Biology
- Molecular Biology
Background:
- Bistability enables cells to adopt distinct stable states, crucial for cell fate decisions, cellular diversity, and cell cycle regulation.
- Positive feedback loops are essential for bistability, with ultrasensitive reactions broadening the parameter range and enhancing state robustness.
- Quantifying bistable ranges is challenging due to noise and transient dynamics causing state transitions.
Purpose of the Study:
- To develop a reliable method for determining the bistable parameter range in synthetic gene feedback loops.
- To investigate the influence of inducer concentration and promoter dynamic range on bistability in yeast.
- To assess the robustness of cellular states and the exploitation of ultrasensitive reactions within these feedback systems.
Main Methods:
- Utilized a threshold of transition rates, coinciding with open-loop bistability boundaries, to estimate parameter ranges.
- Analyzed synthetic single-gene positive feedback loops in yeast within a two-dimensional parameter space.
- Investigated the relationship between promoter dynamic range, inducer concentration, and the emergence of bistability.
Main Results:
- A threshold of transition rates was identified as a reliable indicator for bistability boundaries.
- Promoter dynamic range was found to be a more informative parameter than inducer concentration for assessing bistability.
- The narrowest promoter dynamic range for bistability emergence indicated the effective utilization of ultrasensitive reactions.
Conclusions:
- The developed threshold method provides a practical approach to estimate and compare the robustness of synthetic gene feedback loops.
- Promoter dynamic range serves as a key metric for evaluating the design and performance of bistable systems.
- Controlling basal expression to adjust promoter dynamic range offers a viable strategy for robust synthetic biology applications.
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