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Applications

Besides being a nice model for describing learning behavior or epigenetics, our system-structure can also be used for potent real world applications:

Multipurpose Cell Lines

Our system can be trained to behave in a specific way by setting its inducible toggle switch to one of its two states. Let’s say this specific states trigger specific and different events such as enzyme synthesis, transcriptional regulation, virion production or cell death. In this case one can view the bacterial cell line containing this system as a multipurpose cell line. Put another way: One has a cell line and adds a certain chemical to train it to the desired behaviour instead of constructing two independent cell lines. This means, one applies an “input engineering” instead of a “DNA engineering” approach. If one extends this idea to several inducible toggle switches being harboured in the same cell line, the number of possible phenotypes increases to 2ⁿ, whereas n equals the number of toggle switches. For example, if one would have 5 toggle switches inside a cell line, 32 different behaviour patterns would be possible.

Intelligent Biosensors and Self-Adaptation

As a direct application of the multipurpose cell lines mentioned above, we constructed a system capable of sensing different chemicals and producing different fluorescent proteins. Since the cells can be trained to produce one of several specific fluorescent protein types when a certain chemical is present, one can also view those cells as intelligent biosensors, able to change their properties in a training phase.
It can also be possible that the environment (and its chemicals) itself is the training phase and hence that the biosensors are adapting themselves to this environment and hence the desired state.
Eventually, the intelligent biosensors are not limited to dedect chemicals. Also temperature, pH or light etc. could be detected with an appropriate system.

Link to Epigenetics

Epigenetics refers to features like chromatin or DNA modifications that do not involve changes in the underlying DNA sequence and are stable over many cell divisions [1],[2]. If one has a closer look at our proposed system, one can also view it as a model-system for epigenetics: Although the DNA sequence itself stays the same, two different subpopulations of cells with different phenotypes can develop from it. Put simply, depending in which state (subpopulation) the toggle switch is, the cells will produce different fluorescent proteins upon addition of inducer molecules (aTc or IPTG). For example, if aTc is added one subpopulation will be red while the other will be yellow although both carry exactly the same DNA information. Therefore, the epigenetic feature here is the binding of specific repressor proteins whose production is dependent on the toggle switch state.

References

[http://www.nature.com/nature/journal/v447/n7143/abs/nature05913.html;jsessionid=62903C604764B175945C03DB8639ECBD [1] Bird A] "Perceptions of epigenetics", Nature 447:396-398, 2007
[http://linkinghub.elsevier.com/retrieve/pii/S096098220701007X [2] Ptashne M] "On the use of the word ‘epigenetic’", Current Biology 17(7):R233-R236, 2007