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Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
An excitable gene regulatory circuit induces transient cellular differentiation
Gürol M Süel1, Jordi Garcia-Ojalvo, Louisa M Liberman
1Division of Biology and Department of Applied Physics, California Institute of Technology, Pasadena, California 91125, USA.
Nature
|March 24, 2006
Summary
Bacillus subtilis competence, a transient cellular state for DNA uptake, is regulated by an excitable genetic circuit. This circuit
Area of Science:
- Microbiology
- Systems Biology
- Molecular Biology
Background:
- Cellular differentiation can be probabilistic and transient, with cells switching states and returning.
- In Bacillus subtilis, competence is a transient state enabling environmental DNA uptake.
- The dynamic gene interactions controlling entry and exit from competence were previously unclear.
Purpose of the Study:
- To elucidate the dynamic genetic interactions governing Bacillus subtilis competence.
- To understand the mechanisms of spontaneous entry into and exit from the competent state.
- To model the genetic circuit underlying transient cellular differentiation.
Main Methods:
- Quantitative fluorescence time-lapse microscopy to observe multiple gene activities in single cells.
- Mathematical modeling to analyze the dynamics of the genetic circuit.
- Experimental validation through sister cell analysis and gene circuit re-engineering.
Main Results:
- A genetic circuit exhibiting excitable dynamics explains both entry and exit from competence.
- An excitable core module with feedback loops governs the transient competent state.
- Noise-driven excitable dynamics naturally generate stochastic and transient cellular responses.
Conclusions:
- Excitable dynamics in the genetic circuit provide a robust mechanism for regulating Bacillus subtilis competence.
- This model explains the probabilistic and transient nature of competence differentiation.
- The findings offer insights into the regulation of transient cellular states in other biological systems.
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