Team:NTU-Singapore/Parts/Parameter Estimation using Characterization Results

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Contents

Lactose Induced GFP production


GFP Production Model in  Simulink

GFP Production Model

RFU Results



In the above two figures, we have a comparison between the model generated by our very own equations versus the RFU results that we have obtained using our characterization procedures. There are certain features that are our outstanding when these two figures are compared.

1)The deterministic model has not captured any of the stochastic features the real situation presented before us. 2)The model seems to hit steady state much faster than the actual situation

Careful observation of the results from the characterisation and one would notice that the output takes on the form of a sigmoid curve. Indeed, one of the major flaws in our modeling exercise was that the models don't account for cell growth. Even though we used M9 medium to do our characterisation, it is impossible to assume the cells don't multiply and grow within the 12 hour time period!

This prompts us to look into a better model such that we can first capture the essentials of the real situation before we decide to use our models with our characterisation results

Creating a Logistic Growth Construct

The logistic growth model is typically applied to growth kinetics of Microbes and other natural phenomena. This phenomena is based on the fact that no population can expand exponentially forever and there will be a certain limit to the number of species based on the space that is available.

Here we explore the results of three Logistic Growth equations and their various outputs to see how well the results turn out to be.

Logistic Growth Model

Logisitic Growth equation Logisitic Growth Model
N = number of species in the population
t = time
Nmax = Maximum number of species in the ecosystem
r = intrinsic rate of natural increase

Logistic Growth Model with lag phase

Logisitic Growth equation with lag phase Logisitic Growth Model
Nmin = Minimum number of species in the ecosystem
c = Adjustment factor

Logistic Growth Model with Varying Carrying Capacity

Logisitic sine Growth equation Logisitic Growth Model

Building the Construct

Revisiting the general idea of our modeling, we have treated each bacteria cell to work as a CSTR (Continuous stirred Reactor).

Bacteria equal CSTR

However, each bacteria is itself a reactor and these "mini reactors" multiply and grow~! Therefore we want our new model to be able to account for both the production of proteins and the growth pattern of the bacteria. So now instead of a simple basal signal into our model, we would send in a signal that codes for a "logistic growth" in the basal transcription of the model.
GFP Production Model in Simulink

GFP Production Model Result
As seen, the logistic input can still capture varying lactose inputs and this model seems to be a more representative one for the characterization results.

References

1. A new logistic model for Escherichia coli growth at constant and dynamic temperatures FUJIKAWA Hiroshi ; KAI Akemi ; MOROZUMI Satoshi

2. www.oakenstaff.org/munin/biolmodcontrols/pdfs/populationdynamicsr1.pdf