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Contents 1 Intro 2 Principle 3 Implementation 3.1 The Clock Design 3.2 The Counter/Display Design 4 Challenges 5 References 6 Discussion

Intro

The Oscillation Counter is a genetic circuit module that activates the production of a gene every other peak. The ultimate goal is to combine such modules to count to an arbitrary number. Therefore, this project is cool, and every effort should be put to bring it to reality.

Principle

The first part of the module discretizes the analogue oscillation of concentrations of a substance A into two states - ON and OFF - and can be seen as an alternating toggle switch or as the clock of the system.

Based on this basic clock, a counter module based on a cascade reaction or even layers of such modules could be added.

Implementation

The Clock Design

This part takes as input the concentration of the oscillating substance and leads to the all-or-none response S.

                   _   _   _
/\/\/\/\/\/\  -> _| |_| |_|
                 
         States: 0 1 0 1 0 1
         (0 = OFF, 1 = ON)

Could this be done through strong cooperativity?

The Counter/Display Design

One could assign the system four different states as opposed to only two:

                   _   _   _
/\/\/\/\/\/\  -> _| |_| |_|
                 
         States: 0 1 2 3 0 1

The counter would keep track of the succession of those four states, i.e. count alternations of S up to four. It would response during - and only during! - state 0 and finally flash at state 3:

                           ,- - - - - - - - - - - - - - - - 
                          v                 , - - - - -     \ 
  gene0    --<xSx>-AND-<ig3i>---==============--       |  
                           ,- - - - - - - - - - - - - -      |
                          v                 , - - - - -    
  gene1    --<iSi>-AND-<ig0i>---==============--       |     |
                           ,- - - - - - - - - - - - - -   
                          v                 , - - - - -      |
  gene2    --<xSx>-AND-<ig1i>---==============--       |  
                           ,- - - - - - - - - - - - - -      |
                          v                 , - - - - - - - - - - -> Reporter gene (e.g. GFP)
  gene3    --<iSi>-AND-<ig2i>---==============--  
 
  
  legend:
    ===   : gene
    ---   : DNA
    - -   : Regulatory pathway
    <iGi> : promoter region induced by G
    <xGx> : promoter region repressed by G
    

All genes 0 to 3 need to induce strong responses while being quite instable themselves to insure rapid degradation time.

Challenges

• bootstrapping?
• how does noise accumulate and propagate?
• what about delays and timescale?
• do we have a reliable oscillator at all to start with?

References

Discussion

>> for comments, questions and temporary remarks go to the Talk:Oscillation_Counter

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