Ultrasensitivity and noise propagation in a synthetic transcriptional cascade

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Ultrasensitivity and noise propagation in a
synthetic transcriptional cascade

• Sara Hooshangi, Stephan Thiberge, and Ron Weiss
• Presented by
• John Chattaway, Christin Sander

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Introduction

• The paper investigated transcriptional cascades
• Noise
• Sensitivity
• Response Times
• Synchroniation/Cell-cell variability

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Inhibitory Cascades
aTc anhydrotetracycline
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Longer Transcriptional Cascades Have Increased
Steady-State Sensitivity

• Confirms previous theoretical studies
• Sharper steady state transfer in longer cascades

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Response Times

• Increase with cascade length
• Increases length of time before circuit starts to
  react to stimulus
• Circuit 1 120min.
• Circuit 2 400min. (to reach steady-state)
• Circuit 3 600min.

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CellCell Variability

• Cell-cell variability increases with longer
  cascades
• Noise in transition region is amplified as
  cascade becomes longer

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Synchronization of Cell Responses

• Hardly any variation in Circuit 1
• Peak in variation during signal transduction in
  Circuit 3

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Low-Pass Filters
5min. 45min. 60min.
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Matching kinetic rates

• Need to match kinetic rates of enzymes to output
  of gene
• All genes in the system need to have similar
  rates of transcription and activation

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Effects in nature

• Division
• Stochastic Nature of reactions
• Small number of molecules / longer cascades

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Questions Answers