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Revision as of 11:47, 19 October 2010

Mathematical Modeling Overview

Schematical overview of the devices and change upon light pulse induction. LSP refers to light switch protein, AP to anchor protein, anchor to the plasmid anchor and Che to the attacked protein of the chemotaxis pathway.

In order to support wet laboratory experiments and to create a test bench for the information processing part, a molecular model of E. lemming was created. This goal was achieved by implementing and combining deterministic and probabilistic molecular models of the individual parts.

The core component of E. lemming is the fusion of one light-sensitive protein (LSP1) to a protein of the chemotaxis pathway (Che). Upon change of wavelength of light pulses, this component will dimerize with the corresponding light-sensitive protein (LSP2), which is linked to an anchor protein, bound to an anchor (plasmid). The result is a change of the spatial localization of Che and perturbation of the chemotaxis pathway, which ultimately leads to a different tumbling/directed movement state ratio.

Implementation of mathematical models

Individual molecular models

In a first step, we implemented individual molecular models of subdevices.

• Light Switch: based upon the light-sensitive dimerizing Arabidopsis proteins PhyB and PIF3.
• Chemotaxis: two similar models of the chemotactic receptor pathway.
• Movement: a probabilistic model of E. coli movement, determined by distribution of input bias.

Combined molecular models

Combined models. Coupled individual models for the simulation of the whole process and their interfaces.

The next step, combination of the individual molecular models to a comprehensive model of E. lemming was achieved in two substeps:

• Light switch - Chemotaxis: used to provide support for wet laboratory.
• Chemotaxis - Movement: complete mathematical model.

Interworking: From mathematical modeling to biology and back

Insights for wet laboratory

To create the biological implementation of E. lemming, the parts of the core components had to be chosen in an order to improve chances to result in a functioning ensemble. By using the combined molecular models for in silico evaluation of the best possible parts, it was possible to reduce the amount of different combinations to be tested.

Wet laboratory evaluation results have showed, that molecular modeling and experimental biology can collaborate to gain new insight for both perceptions of the problem.

Insights for information processing

In order to adjust the controller to have optimal light pulse rates, the combined molecular model has been used to determine the corresponding time constants.

Information processing evaluation results provide further information how this has been accomplished.

Test bench for information processing

Test bench for information processing.

In order to create a first test bench for the information processing pipeline, the combined molecular models have been used to create and evaluate the controller. By providing an input port for light pulse and an output port for movement, it was possible to close the loop and simulate the whole system.