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Ultrasensitivity and noise propagation in a synthetic transcriptional cascade

Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Sara Hooshangi, Stephan Thiberge, and Ron Weiss Presented by John Chattaway, Christin Sander. Introduction. The paper investigated transcriptional cascades Noise Sensitivity Response Times

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Ultrasensitivity and noise propagation in a synthetic transcriptional cascade

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  1. Ultrasensitivity and noise propagation in a synthetic transcriptional cascade Sara Hooshangi, Stephan Thiberge, and Ron Weiss Presented by John Chattaway, Christin Sander

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

  3. Inhibitory Cascades aTc: anhydrotetracycline

  4. Longer Transcriptional Cascades Have Increased Steady-State Sensitivity • Confirms previous theoretical studies • Sharper steady state transfer in longer cascades

  5. 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.

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

  7. Synchronization of Cell Responses • Hardly any variation in Circuit 1 • Peak in variation during signal transduction in Circuit 3

  8. Low-Pass Filters 5min. 45min. 60min.

  9. 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

  10. Effects in nature • Division • Stochastic Nature of reactions • Small number of molecules / longer cascades

  11. Questions & Answers

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