Team:ETHZ Basel/Modeling
From 2010.igem.org
E-Lemming @ ETHZ – Modeling Overview
ETHZ’s project, E-Lemming, aims to modify the chemotaxis property of E.coli such that, instead of response to a chemical attractant/repellent, the bacterium responds to a light stimulus (phototaxis). Furthermore, this light sensitivity is used to control E.coli’s movement by deciding, at any given time, which type of motion will our ‘Lemming – in – disguise’ adopt (tumbling or straight run). This leads to a controllable E.coli, which can follow any pre – defined spatial path/maze/game, as a result of the combination of tumbling and going straight. The bacterium colony is imaged and, by image processing, the position of a single tracked cell is inferred. By activating a light switch, the user decides whether the bacterium should continue running or should change direction.
In the theory world, the steps we are following in mindlessly driving E.coli to our pre - defined target are the following:
• deterministic (ODE) & stochastic models of the chemotaxis pathway (documented from the literature)
• model of the movement of E.coli (built on the information of the pathway derived from the molecular models)
• control algorithms ( built on the user’s desire to play around with E.coli)
• image tracking & image processing algorithms
• java applications/movies of the E.Lemming (the fun part)
Molecular Models
The network topology
Many bacteria posses a signal transduction network that makes it possible to sense the changes in concentration of a certain chemical attractant/repellent in the extracellular environment and direct the movement towards the attractant and away from the repellent. This property is what is known as ‘chemotaxis’. There are basically two types of movement that the bacterium can employ: 'tumbling', which means change of direction and occurs when the bacterium doesn’t sense an increase of attractant concentration in the extracellular environment anymore and 'running straight', which occurs when the attractant concentration is increasing. The running straight stands for “correct direction, ok, keep going” (towards the attractant/away from repellent) while the tumbling stands for “wrong direction, give it another shot”. In the case of E.coli, these two types of movements correspond to different rotation directions of its 4 flagellar motors (clockwise: tumbling; counter-clockwise: runs).
The direction of rotation of the motors can be determined by the ratio of concentrations of certain proteins inside the cell. That is, there are some quantitative indicators from which one can infer whether the bacterium will run or it will go straight, as a response to changes in input concentration. These indicators (concentration levels for certain proteins) are the result of a well – studied signal transduction network, consisting of membrane receptor proteins and intracellular proteins (Che).
Our models were constructed based on the following network topology:
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