IGEM:IMPERIAL/2006/project/Oscillator/Theoretical Analyses/3Dto2D

Analysis of the Model of the Molecular Predation Oscillator

• Introduction
• Our Approach
• Model Simplication
• Our Results
• Conclusion
• Appendix

Model Simplification

• Why we can simplify the 3d Model into a 2D Model

• Simplification is possible because of the similarity of the growth rates of the predator terms (V and W) in the 3D Model

• Their complex production terms are identical
• Only their dissipative terms (-d1*V and -d2*W ) varies

• A simple hypotheses could lead to a very big simplification in our analysis
• A 2D analysis is much simpler, and still will give us valid prediction on whether the system will oscillate.

• Required Hypotheses for Simplification

• Hypothesis 1: to ensure V and W have same growth rates

• Hypothesis 1: d1=d2)

• Hypothesis 2:To have equality of the initial conditions

• Hypothesis 2: [aiiA] = [LuxR] at time t=0

• Under previous 2 Hypotheses

• aiiA and LuxR start at the same concentration
• they have the same rate of production and degradation
• hence they have at the same concentration throughout

• System then can be simplified to

• Validity of the hypotheses

• Hypothesis 1 : d1=d2

• The assumption of d1=d2 is feasible because aiiA and LuxR within the cells will be washed out at the same rate in chemostat.
• As long as we can ensure the washing out rate is much more dominant than their natural half-life (easily achieved) the assumption should hold

• Hypothesis 2 is not really essential

• it is fortunate as it was hard to ensure
• if d1=d2, the difference between W and V will decay to 0 exponentially (with a time constant 1/d1)
• therefore after a little time we can assume V=W
• the larger d1, the faster the assumption becomes valid
• the larger the difference between initial values of V & W, the longer the settling time of reaching V=W only
• In particular we are sure that the condition on the parameters for obtaining a limit cycle will still be identical in 2D and 3D despite of the initial concentrations of U V W.

• Problem : in Theory , there is a Huge Difference Between 2D and 3D</font size="4

• Poincare-Bendixson Theorem works for 1D and 2D only, but not 3D

• We only need simple requirements for a limit cycle in 2D
• In 3D the requirement is more complex - or much more complex

• So are our results in 2D worth anything ?

• If our hypotheses are exactly met: Yes!
• In practice hypotheses not exactly met, but we have a margin of error
• A slight error on Hypothesis 2 is not important
• Slight error on hypothesis 1 (d1 not strictly equal to d2): 2 Scenarii

• Scenario 1: (the kind one)

• For d1=d2 and a range of parameters well chosen we have oscillations
• Because the system is well behaved , we still have oscillations at the vicinity of these parameters (hence for d1 slightly different from d2)

• Scenario 2: (the not so nice one)

• [aiiA] and [LuxR] get more and more out of synchronisation
• However, if the hypotheses are almost met, we can hope to have a few synchronised cycles

• Conclusion

• There is a lot to learn from the 2D model
• A word of caution:

Simulation of Full 3D model done by Cell Designer

• The simulation above shows individual cycles of [aiiA] and [LuxR]
  • Frequencies are equal
  • Profiles very similar
  • Peak amplitudes different
  • Clearly for such cycles d1=d2 was not met and yet we have oscillations. We therefore have to study the 3D case in its entirety at some point
• However for our current interest of whether the system can result in generation, 2D case of d1=d2 should be enough