Team:Aberdeen Scotland/modeling/combined model

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==Combined Chemotaxis and Lysis Model==
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=Combined Chemotaxis, Lysis and Glue Deposition Model=
=Introduction=
=Introduction=
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In order to examine how the system as a whole behaves it is necessary to combine the results of modelling the gene regulatory network with a macroscopic model of interacting <i>E. Coli</i> cells. This was done by estimating that quorum sensing becomes activated when the density of bacteria around the source of chemoattractant goes above a critical value, and then saying that after a given time calculated from the stochastic model the cells will then lyse.
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In order to examine how the system as a whole behaves it is necessary to combine the results of modelling the gene regulatory network with a macroscopic model of interacting <i>E. Coli</i> cells. This was done by estimating that quorum sensing becomes activated when the density of bacteria around the source of chemoattractant goes above a critical value. The radius within which quorum sensing is activated varies over time, and depends on how many bacteria there are. We combine the lysis time calculated from our stochastic simulations with this model so that this amount of time after quorum sensing is activated the bacteria lyse and deposit glue.
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==Results==
==Results==
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The graph below shows the effective radius in which the bacteria have activated quorum sensing:
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In the simulation we assume the bacteria to be distributed throughout the pipeline so that they continually arrive at the breach by chemotaxis. The graph below shows the number of alive bacteria at the site of the breach:
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As you can see, the radius increases from point 1 to a stable
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As you can see in the above graph the number of bacteria increases initially as bacteria arrive from the surrounding area. It eventually reaches an equilibrium value as the rate of bacteria lysing equals the rate of arriving bacteria.
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As the bacteria number reaches an equilibrium the effective radius within which the bacteria quorum sense also reaches an equilibrium, as illustrated below at point 3.
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The above graph and diagram show the progression of the quorum sensing region as bacteria continue to arrive. As there is a constant rate of lysing bacteria, there is a linear increase in glue concentration at the breach, as illustrated below:
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finish this liam!!!!!!!!!!!
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The increase in glue concentration does not stop, as we have not modelled the eventual sealing of the hole. Once the hole is sealed the chemoattractant gradient would dissipate, along with the signalling molecule IPTG. Eventually the genes for lysis and glue production would no longer be activated and the glue concentration would stop increasing.
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==Conclusions and Results==
==Conclusions and Results==
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This model shows, assuming that the gene regulatory network behaves as expected, that the <i>E. Coli</i> would chemotax, activate and deposit glue. Actual experiments would need to be done with lysing cells that actually deposit glue, and if the glue seals the hole. As the glue production does not stop until the IPTG is gone, it can be assumed that the hole would actually be sealed, the size of the glue plug is however uncertain.
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Revision as of 19:33, 21 October 2009

University of Aberdeen iGEM 2009

Contents

Combined Chemotaxis, Lysis and Glue Deposition Model

Introduction

In order to examine how the system as a whole behaves it is necessary to combine the results of modelling the gene regulatory network with a macroscopic model of interacting E. Coli cells. This was done by estimating that quorum sensing becomes activated when the density of bacteria around the source of chemoattractant goes above a critical value. The radius within which quorum sensing is activated varies over time, and depends on how many bacteria there are. We combine the lysis time calculated from our stochastic simulations with this model so that this amount of time after quorum sensing is activated the bacteria lyse and deposit glue.



Results

In the simulation we assume the bacteria to be distributed throughout the pipeline so that they continually arrive at the breach by chemotaxis. The graph below shows the number of alive bacteria at the site of the breach:

As you can see in the above graph the number of bacteria increases initially as bacteria arrive from the surrounding area. It eventually reaches an equilibrium value as the rate of bacteria lysing equals the rate of arriving bacteria.

As the bacteria number reaches an equilibrium the effective radius within which the bacteria quorum sense also reaches an equilibrium, as illustrated below at point 3.

The above graph and diagram show the progression of the quorum sensing region as bacteria continue to arrive. As there is a constant rate of lysing bacteria, there is a linear increase in glue concentration at the breach, as illustrated below:


The increase in glue concentration does not stop, as we have not modelled the eventual sealing of the hole. Once the hole is sealed the chemoattractant gradient would dissipate, along with the signalling molecule IPTG. Eventually the genes for lysis and glue production would no longer be activated and the glue concentration would stop increasing.

Conclusions and Results

This model shows, assuming that the gene regulatory network behaves as expected, that the E. Coli would chemotax, activate and deposit glue. Actual experiments would need to be done with lysing cells that actually deposit glue, and if the glue seals the hole. As the glue production does not stop until the IPTG is gone, it can be assumed that the hole would actually be sealed, the size of the glue plug is however uncertain.


References

[1] A.B. Goryachev, D.J. Toh, T. Lee. “Systems analysis of a quorum sensing network: Design constraints imposed by the functional requirements, network topology and kinetic constants”. BioSystems 83 (2006) 178–187

[2] Michail Stamatakis and Nikos V. Manttaris. “Comparison of Deterministic and Stochastic Models of the lac Operon Genetic Network” Biophysical Journal Volume 96 February 2009 887-906 887