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Digital Logic in Synthetic Biology

A large chunk of effort in synthetic biology has been aimed at attempting to view genes as parts of a circuit. Thus, a lot of focus has been directed toward creating biological analogues of digital logic gates, such as an AND or a NOT gate, which give a digital 1 or 0 response, depending on the truth table of the gate.
However, there is a serious issue in the scale up of these circuits. While that can be attributed to several reasons, one of the major reasons is this simplification under which the systems work. We can see that the output response from the gate is not close to the actual digital “1 or 0” kind that one would ideally want from a logic gate, and in the range that is neither in the ON nor the OFF regime, the response is really graded.



NThus, when a combination of gates is used in conjunction, one could not expect them to remain digital. Just imagine using a 10 input AND gate as shown below, that could possibly be used as an environmental biosensor. If the concentration of a few inputs is in the ON range, while the others are in the middle range, should the device show an ON or an OFF state? It may show neither, as we have seen above, leaving the researcher confused as to how the results must be perceived.

High Cooperativity Repressors – A Possible Solution<\u>

The solution to the problem lies in the cooperativity of the parts that are used as actuators in these digital devices. These are mostly created using repressors or activators, which can repress or activate their respective promoters. Cooperativity is basically the phenomenon where the repressor (or activator) molecules do not act independently of each other, and two or more molecules of the same are needed to first bind to each other, before binding to the promoter that they are to repress.
What this means is that if the cooperativity of the repressor is “n”, then unless n molecules of the repressor combine, they would not be able to repress the promoter and control gene expression. This kind of behavior becomes desirable, since when low quantities of the repressor are present, we would expect lesser repression in the case of a high cooperativity repressor. This would generate a response that would be closer to the digital output, which is desired. This is further explained in the modeling section, but just for a brief idea, here is what the picture looks like, for increasing cooperativity.
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