Impact of switches

A switch is the basic regulatory element that can maintain a selected state even in the absence of a signal. Introduction of several orthogonal bistable switches allows selection of many different states, e.g. 3 bistable switches allow 8 distinct states while 1000 different states could be reached with only 10 switches.

Each state of our switch is defined by the presence of selected orthogonal activators and repressors than can in principle regulate any number of selected genes through the same activator. Therefore with a relatively small number of designed switches we could drive a very complex epigenetic cell program similarly as it is executed in cell differentiation.

Additionally, switches are the basic building blocks of memory, in analogy to the electronic components. Therefore a set of orthogonal bistable switches can be used to build a biological memory of significantly higher complexity than has been possible up to now.

Scalable biological memory is one of the great challenges of synthetic biology. Memory can be used to design counters, which are extremely useful elements in engineering. Counters have been so far demonstrated to count only up to 3 with no prospects of a significant increase as the number of orthogonal elements used for counting is limited by the availability natural elements, such as recombinases.

We therefore anticipate that designed TAL-based or in general DNA-binding element-based transcriptional factor logic may play a crucial role for the development of synthetic biology.

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