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Modeling a synthetic genetic oscillator,[object Object],Part of an iGem project,[object Object]
iGem,[object Object],Global synthetic biology competition,[object Object],International Genetically Engineered Machine,[object Object],8th year in a row, first time Wageningen UR competes,[object Object],Genetic building blocks,[object Object]
Projects,[object Object]
Synchronized Oscillatory System,[object Object],Negative feedback loops,[object Object],Positive feedback for signaling molecule,[object Object],Signaling molecule synchronizes oscillations,[object Object]
The Danino et. al scheme,[object Object]
Equations from Danino et. al,[object Object]
Advantages of this model,[object Object],4 differential equations,[object Object],Simplified reaction scheme,[object Object],Takes the surrounding physics into account,[object Object],Cell density,[object Object]
Modeling results,[object Object],Equations introduced in Matlab,[object Object],The P function is covered by dde23,[object Object]
Disadvantages of the model,[object Object],Units of parameters,[object Object],Some biologically relevant information missing,[object Object],No useful result can be extracted,[object Object]
Alternative model,[object Object],More biologically relevant and accurate,[object Object]
Modelling a synthetic genetic oscillator
Equations for this model,[object Object],Y1 : lux-I mRNA,[object Object],Y2 : LUX-I protein,[object Object],Y3 : AHL,[object Object],Y4 : AHL-LUX-R complex,[object Object],Y5 : aiia mRNA,[object Object],Y6 : AiiA protein,[object Object],Y7 : AiiA-AHL complex,[object Object],Y8 : gfp mRNA,[object Object],Y9 : GFP,[object Object]
Disadvantages of this model,[object Object],Many parameters,[object Object],A large number of them unknown,[object Object],Does not (yet) take into account flow rates or cell density,[object Object]
The microsieve,[object Object]
Modeling of the microsieve,[object Object],A more global approach,[object Object],Units are more logical,[object Object],A more widely applicable model,[object Object],However:,[object Object],Many measurements are needed to validate the model,[object Object],Many physical units are required,[object Object]
Measurement plans,[object Object],Introduce different flow rates to the system,[object Object],Measure both the outflow and permeate flow (under influence of pressure),[object Object],Introduce a cell suspension to the system,[object Object],Measure flow rates,[object Object]
Goal,[object Object],Produce a model that can estimate a flow rate to achieve:,[object Object],An appropriate cell density,[object Object],A constant oscillation through AHL expression,[object Object]
Questions,[object Object],In which way do we model this most efficiently?,[object Object],Which of these models is actually feasible?,[object Object],Is it possible to combine the models?,[object Object]

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