Figure 7.
Biological signal amplification to boost dynamic range: Genetic amplifiers are ligand‐free ultrasensitive transcription factor and promoter pairs which have a large output dynamic range and can be linked to sensing transcription factors and promoters with low dynamic ranges to increase them. a) The simplest architecture of an amplifier is an activator system with high expression where the responsive promoter (PR) is used to control the expression of the activator (hrpS and hrpR) which then activates the amplifier promoter (PhrpL). The effect of an amplifier on the response curve is shown by the two curves. The level of amplification (amplification gain) can be tuned by adding another level of regulation to the amplifier through a repressor (hrpV).63 b) Alternative architectures can also be used for amplification. i) Positive feedback can be added to increase the amplification on induction placing the amplifier protein (amp) under the control of the amplifier promoter (Pamp) and the responsive promoter (PR).64 ii) Amplifiers have been combined with other techniques to prevent increased leaky expression due to amplification.1 The addition of a degradation tag to the output protein (ParsR) reduces basal expression. Whilst the expression of a protease under the control of the same input promoter can cleave off the degradation tag when the target is present to prevent reduction in the maximal expression.