Oscillator based Attic

From 2006.igem.org

Toggle switch

Idea

During our discussion, it became apparent that another possibiliy to build a counter / divisor would be to use a toggle switch. It seems that the term "toggle switch" is not well-defined, i.e. it can stand for a few different functionalities of electronic circuits.

When I use the term "toggle switch" in this section, it shall stand for a genetic device with one input and one output, where both of them have two possible states (high and low). When the input is low, the output doesn't change (it keeps its current state). When there is a peak in the input signal (i.e. it jumps to the high state but doesn't stays there to long, where the length of "to long" depends on the parameters of the circuit), the output changes to the state opposite to its current state (from low to high or from high to low). It "toggles".

Concept for Implementation

A possible implementation of this concept could look as following:

The first device needed is just a bistable switch, as described in the lecture by Jörg (if someones remembers the paper where this came from, please add a reference to that paper here) <<Might have been Lai04>>

     R1                                   R2    
      \                                   /      
       \/|____                     ____|\/       
    ___/  (1) |_______     _______| (2)  \___ 
       \  ____|  =  =        = =  |____  /     
        \|       |  |        | |       |/        
                 |  |        | |                  
                R2  R3      R4 R1                  
                                             

The bistable switch produces either R1 or R2. When R1 is present, it represses the production of R2. If R2 is present, it represses the production of R1. Thus, this device has two stable states. I will refer to the state where R1 is produced as State 1 and to the state where R2 is produced as State 2. The repressors R3 and R4 should be ignored in this stage, they get their relevance when the second component of the toggle switch is introduced below.

Now, we need another device that allows us to switch the bistable switch from one state to the other. I call it switcher. This could be achieved in the following way:

    S  R1         R3         S  R2         R4
    |  |         /           |  |         /
    |  |   ___|\/            |  |   ___|\/
   _|__|__| (3) \___        _|__|__| (4) \___
          |___  /                  |___  /
              |/                       |/

The idea of the switcher is to repress the production of the repressor (R1 or R2) that is currently produced by the bistable switch. It does so only when the input signal S is present. The concept of the dynamics of a toggling is as folloeing:

Given the bistable switch is currently in state 1 with gene (1) activated and gene (2) repressed. When the concentration 
of S rises, S in combination with R1 leads to the production of R3, which itself cuts of the production of R1, allowing
R2 to be produced. The bistable switch has been toggled.

Challenges

To make this device work, one has to adjust the time constants. There are some challenges to face:

• Assume the bistable switch has just been toggled from state 1 to state 2. When S is still present, R2 produced in state 2 can lead to a retoggling to state 1. This behavior is clearly undesired. To avoid this, S should be a substance that is degraded quickly.
• Even when S has sharp peaks, there is still a problem during transition. Given the toggle switch is in state 1. S rises, R3 is produced, and the production of R1 in reality is rather first lowered than directly cut off. This leads to a lower production of R3, thus slowing down the toggle process. To avoid this, R3 should be stable on a longer timescale than the timescale of the processes in the toggle switch. If this is ensured, a short peak of S is sufficient to produce some persistent R3, that is able to stop the production of R1. This allows one to make the peak short enough to guarantee that the above described "double toggling" does not happen.

Using the toggle switch as a counter

If you have such a device working, it is possible to convert an input signal with frequency to a signal with frequency 2f. This is a divisor. If you combine n of these divisors, you are able to count to 2^n. That's a counter!

Evaluation of the idea

I think that this concept can be implemented. The problems described above should be possible to deal with. I expect the toggle switch to be quite stable and noise resistant, and yet sufficiently simple regarding the different interactions. The catenation of the toggle switches to a counter may prove to be not so easy. A toggle switch is a device, that can be used in a wide area of applications, given the importance of the concept in electrical engineering and computer science.

A test-tube that changes its color from red to green when some substance is added, is not so spectacular, since we all saw this in our high school chemical class. A tube changes back fron green to red when another chemical is added, is slightly better. But what a cool demo, when the tube switches it's color again and again, every time ONE SINGLE SUBSTANCE is added! (for comments and opinions to the coolness of such a demo, please use the talk page...))