Comparison of Deterministic and Stochastic Models of the lac Operon Genetic Network

Stamatakis, Michail; Mantzaris, Nikos V.

doi:10.1016/j.bpj.2008.10.028

Cited by 48 publications

(58 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S3a,b) that was based, in part, on the deterministic equations described by Goryachev et al 31 and Stamatakis and Mantzaris. 32 Briefly, for the lux/lac model, the inductant, IPTG, which can freely diffuse into and out of the cell through the membrane, 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 binds to lacI and promotes production of luxI-LVA and GFP-LVA. LuxI-LVA produces 3OC 6 HSL, which in turn can diffuse out through the cell membrane.…”

Section: Simulation Of Dynamic Gene Expressionmentioning

confidence: 97%

Wiring Together Synthetic Bacterial Consortia to Create a Biological Integrated Circuit

2016

View full text Add to dashboard Cite

The promise of adapting biology to information processing will not be realized until engineered gene circuits, operating in different cell populations, can be wired together to express a predictable function. Here, elementary biological integrated circuits (BICs), consisting of two sets of transmitter and receiver gene circuit modules with embedded memory placed in separate cell populations, were meticulously assembled using live cell lithography and wired together by the mass transport of quorum-sensing (QS) signal molecules to form two isolated communication links (comlinks). The comlink dynamics were tested by broadcasting "clock" pulses of inducers into the networks and measuring the responses of functionally linked fluorescent reporters, and then modeled through simulations that realistically captured the protein production and molecular transport. These results show that the comlinks were isolated and each mimicked aspects of the synchronous, sequential networks used in digital computing. The observations about the flow conditions, derived from numerical simulations, and the biofilm architectures that foster or silence cell-to-cell communications have implications for everything from decontamination of drinking water to bacterial virulence.

show abstract

Section: Simulation Of Dynamic Gene Expressionmentioning

confidence: 97%

Wiring Together Synthetic Bacterial Consortia to Create a Biological Integrated Circuit

2016

View full text Add to dashboard Cite

show abstract

“…Similarly, the intracellular TMG concentration has been reported to be ∼70-fold higher than the extracellular concentration in fully induced cells [63], [72]. Under pseudo steady state conditions, the ratio of to is related to by the expression .…”

Section: Methodsmentioning

confidence: 98%

Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study

et al. 2011

View full text Add to dashboard Cite

Stochastic expression of genes produces heterogeneity in clonal populations of bacteria under identical conditions. We analyze and compare the behavior of the inducible lac genetic switch using well-stirred and spatially resolved simulations for Escherichia coli cells modeled under fast and slow-growth conditions. Our new kinetic model describing the switching of the lac operon from one phenotype to the other incorporates parameters obtained from recently published in vivo single-molecule fluorescence experiments along with in vitro rate constants. For the well-stirred system, investigation of the intrinsic noise in the circuit as a function of the inducer concentration and in the presence/absence of the feedback mechanism reveals that the noise peaks near the switching threshold. Applying maximum likelihood estimation, we show that the analytic two-state model of gene expression can be used to extract stochastic rates from the simulation data. The simulations also provide mRNA–protein probability landscapes, which demonstrate that switching is the result of crossing both mRNA and protein thresholds. Using cryoelectron tomography of an E. coli cell and data from proteomics studies, we construct spatial in vivo models of cells and quantify the noise contributions and effects on repressor rebinding due to cell structure and crowding in the cytoplasm. Compared to systems without spatial heterogeneity, the model for the fast-growth cells predicts a slight decrease in the overall noise and an increase in the repressors rebinding rate due to anomalous subdiffusion. The tomograms for E. coli grown under slow-growth conditions identify the positions of the ribosomes and the condensed nucleoid. The smaller slow-growth cells have increased mRNA localization and a larger internal inducer concentration, leading to a significant decrease in the lifetime of the repressor–operator complex and an increase in the frequency of transcriptional bursts.

show abstract

“…The most suitable model to describe the investigated phenomenon can be difficult to identify and the use of models of a different nature (i.e., empirical [18,22] or mechanistic [23,24] models) might be necessary to individuate the best candidate [20].…”

Section: Mechanistic and Empirical Modelsmentioning

confidence: 99%

Modelling for Synthetic Biology

Pasotti

Zucca

Magni

2014

Modelling Methodology for Physiology and Medicine

View full text Add to dashboard Cite

Comparison of Deterministic and Stochastic Models of the lac Operon Genetic Network

Cited by 48 publications

References 71 publications

Wiring Together Synthetic Bacterial Consortia to Create a Biological Integrated Circuit

Wiring Together Synthetic Bacterial Consortia to Create a Biological Integrated Circuit

Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study

Modelling for Synthetic Biology

Contact Info

Product

Resources

About