Team:Paris/Analysis/Design1

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Network Design - Part 1


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Generating a FIFO sequential order of expression

A clock that would only indicate one hour, would not be very useful. The same goes for our BacteriO'clock. It is necessary that we add several distinct events in each cycle. We want to use three genes activated successively.

The easiest way to control a sequential expression of genes : the LIFO order

The washing of dirty plates traditionally follows a LIFO order : the last plate put on the stack is the first one to be washed
Network 1 : The Single Input Module can generate a LIFO temporal order.


The temporal order of expression that is the easiest to set up is the Last In First Out temporal order. The genetic network that generates this behavior is the Single Input Module (SIM) (Network 1). A transcription factor X activates the expression of different genes Zi. When X concentration increases, the threshold of activation Ki of the different genes Z are reached in a precise order. The expression will stop in the opposite order when X is not expressed anymore. To cut a long story short, the first gene to be switched on will be the last one to be OFF.

This order poses a real problem to us : several states of the system are redundant (Table 1). We can not accept a clock that would display twice the same hour !

The rules to generate a FIFO temporal order

Table 1 : Comparison of the LIFO and the FIFO orders. (● : gene is OFF, O : gene is ON)

In the contrary, in a FIFO order, there is no confusion possible between different states : they are all distincts. To generate this complex behavior, there are two major possibilities.

The simplest way to generate a FIFO : a simple cascade of genes

Network 2 : A cascade of gene : the simplest way to generate a FIFO behavior.

The first one, the simplest, which is also the most unsophisticated, is a simple cascade of genes (Network 2). When the first gene Z1 is switched on, it activates the second gene Z2, then the third gene Z3 is turned on. When gene Z1 is turned off, Z2 is switched off first, then Z3...

This network is really simple to implement but presents several problems that makes it incompatible with our project. First of all, the cascade is not resistant to mutations : when one gene is mutated, the cascade is definitely broken. Secondly, the time scale if far too long. Each activation step would take approximately one hour. One full cycle would last almost six hours. Last but not least, the cascade is probably not very resistant to intracellular noise, it is not robust enough.

The more sophisticated way to generate a FIFO behavior : a particular Multiple Output Feed-Forward Loop

Implementation of our FIFO

In the FIFO you could start by saying we were looking for a FIFO and rather than designing it from scratch we decided to look in nature where we found and adopted the flagella which then inspired us further

Previous step : Project Description

Next step : Network Design Part 2 : Oscillations