TY - JOUR
T1 - Isolating intrinsic noise sources in a stochastic genetic switch
AU - Newby, Jay M.
N1 - KAUST Repository Item: Exported on 2021-09-17
Acknowledged KAUST grant number(s): KUK-C1-013-4
Acknowledgements: JMN would like to thank James P Keener for valuable discussions throughout this project. This work was supported by award no KUK-C1-013-4 made by King Abdullah University of Science and Technology (KAUST).
This publication acknowledges KAUST support, but has no KAUST affiliated authors.
PY - 2012
Y1 - 2012
N2 - The stochastic mutual repressor model is analysed using perturbation methods. This simple model of a gene circuit consists of two genes and three promotor states. Either of the two protein products can dimerize, forming a repressor molecule that binds to the promotor of the other gene. When the repressor is bound to a promotor, the corresponding gene is not transcribed and no protein is produced. Either one of the promotors can be repressed at any given time or both can be unrepressed, leaving three possible promotor states. This model is analysed in its bistable regime in which the deterministic limit exhibits two stable fixed points and an unstable saddle, and the case of small noise is considered. On small timescales, the stochastic process fluctuates near one of the stable fixed points, and on large timescales, a metastable transition can occur, where fluctuations drive the system past the unstable saddle to the other stable fixed point. To explore how different intrinsic noise sources affect these transitions, fluctuations in protein production and degradation are eliminated, leaving fluctuations in the promotor state as the only source of noise in the system. The process without protein noise is then compared to the process with weak protein noise using perturbation methods and Monte Carlo simulations. It is found that some significant differences in the random process emerge when the intrinsic noise source is removed. © 2012 IOP Publishing Ltd.
AB - The stochastic mutual repressor model is analysed using perturbation methods. This simple model of a gene circuit consists of two genes and three promotor states. Either of the two protein products can dimerize, forming a repressor molecule that binds to the promotor of the other gene. When the repressor is bound to a promotor, the corresponding gene is not transcribed and no protein is produced. Either one of the promotors can be repressed at any given time or both can be unrepressed, leaving three possible promotor states. This model is analysed in its bistable regime in which the deterministic limit exhibits two stable fixed points and an unstable saddle, and the case of small noise is considered. On small timescales, the stochastic process fluctuates near one of the stable fixed points, and on large timescales, a metastable transition can occur, where fluctuations drive the system past the unstable saddle to the other stable fixed point. To explore how different intrinsic noise sources affect these transitions, fluctuations in protein production and degradation are eliminated, leaving fluctuations in the promotor state as the only source of noise in the system. The process without protein noise is then compared to the process with weak protein noise using perturbation methods and Monte Carlo simulations. It is found that some significant differences in the random process emerge when the intrinsic noise source is removed. © 2012 IOP Publishing Ltd.
UR - http://hdl.handle.net/10754/671268
UR - https://iopscience.iop.org/article/10.1088/1478-3975/9/2/026002
UR - http://www.scopus.com/inward/record.url?scp=84859575994&partnerID=8YFLogxK
U2 - 10.1088/1478-3975/9/2/026002
DO - 10.1088/1478-3975/9/2/026002
M3 - Article
SN - 1478-3975
VL - 9
SP - 026002
JO - Physical Biology
JF - Physical Biology
IS - 2
ER -