article · 01/01/2013
Caveats in modeling a common motif in genetic circuits
Résumé
From a coarse-grained perspective, the motif of a self-activating species, activating a second species that acts as its own repressor, is widely found in biological systems, in particular in genetic systems with inherent oscillatory behavior. Here we consider a specific realization of this motif as a genetic circuit, termed the bistable frustrated unit, in which genes are described as directly producing proteins. Upon an improved resolution in time, we focus on the effect that inherent time scales on the underlying scale can have on the bifurcation patterns on a coarser scale. Time scales are set by the binding and unbinding rates of the transcription factors to the promoter regions of the genes. Depending on the ratio of these rates to the decay times of both proteins, the appropriate averaging procedure for obtaining a coarse-grained description changes and leads to sets of deterministic equations, which considerably differ in their bifurcation structure. In particular, the desired intermediate range of regular limit cycles fades away when the binding rates of genes are not fast as compared to the decay time of the proteins. Our analysis illustrates that the common topology of the widely found motif alone does not imply universal features in the dynamics.
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Labavic, D., Nagel, H., Janke, W., & Meyer-Ortmanns, H. (2013). Caveats in modeling a common motif in genetic circuits. Phys. Rev. E, 87(6). https://doi.org/10.1103/PhysRevE.87.062706@article{Labavic2013_360,
author = {Labavic, Darka and Nagel, Hannes and Janke, Wolfhard and Meyer-Ortmanns, Hildegard},
year = {2013},
month = {1},
title = {Caveats in modeling a common motif in genetic circuits},
journal = {Phys. Rev. E},
publisher = {AMER PHYSICAL SOC},
volume = {87},
number = {6},
address = {ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA},
abstract = {From a coarse-grained perspective, the motif of a self-activating species, activating a second species that acts as its own repressor, is widely found in biological systems, in particular in genetic systems with inherent oscillatory behavior. Here we consider a specific realization of this motif as a genetic circuit, termed the bistable frustrated unit, in which genes are described as directly producing proteins. Upon an improved resolution in time, we focus on the effect that inherent time scales on the underlying scale can have on the bifurcation patterns on a coarser scale. Time scales are set by the binding and unbinding rates of the transcription factors to the promoter regions of the genes. Depending on the ratio of these rates to the decay times of both proteins, the appropriate averaging procedure for obtaining a coarse-grained description changes and leads to sets of deterministic equations, which considerably differ in their bifurcation structure. In particular, the desired intermediate range of regular limit cycles fades away when the binding rates of genes are not fast as compared to the decay time of the proteins. Our analysis illustrates that the common topology of the widely found motif alone does not imply universal features in the dynamics.},
url = {http://www.dx.doi.org/10.1103/PhysRevE.87.062706},
doi = {10.1103/PhysRevE.87.062706},
issn = {1539-3755},
}TY - JOUR
AU - Labavic, Darka
AU - Nagel, Hannes
AU - Janke, Wolfhard
AU - Meyer-Ortmanns, Hildegard
PY - 2013
DA - 2013/01/01
TI - Caveats in modeling a common motif in genetic circuits
JO - Phys. Rev. E
VL - 87
IS - 6
PB - AMER PHYSICAL SOC
SN - 1539-3755
AB - From a coarse-grained perspective, the motif of a self-activating species, activating a second species that acts as its own repressor, is widely found in biological systems, in particular in genetic systems with inherent oscillatory behavior. Here we consider a specific realization of this motif as a genetic circuit, termed the bistable frustrated unit, in which genes are described as directly producing proteins. Upon an improved resolution in time, we focus on the effect that inherent time scales on the underlying scale can have on the bifurcation patterns on a coarser scale. Time scales are set by the binding and unbinding rates of the transcription factors to the promoter regions of the genes. Depending on the ratio of these rates to the decay times of both proteins, the appropriate averaging procedure for obtaining a coarse-grained description changes and leads to sets of deterministic equations, which considerably differ in their bifurcation structure. In particular, the desired intermediate range of regular limit cycles fades away when the binding rates of genes are not fast as compared to the decay time of the proteins. Our analysis illustrates that the common topology of the widely found motif alone does not imply universal features in the dynamics.
DO - 10.1103/PhysRevE.87.062706
UR - http://www.dx.doi.org/10.1103/PhysRevE.87.062706
ER -