Ultrasensitivity and noise propagation in a synthetic transcriptional

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Ultrasensitivity and noise propagation in a synthetic transcriptional cascade Sara Hooshangi, Stephan Thiberge, and

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

Introduction n The paper investigated transcriptional cascades ¡ ¡ Noise Sensitivity Response Times Synchroniation/Cell-cell

Introduction n The paper investigated transcriptional cascades ¡ ¡ Noise Sensitivity Response Times Synchroniation/Cell-cell variability

Inhibitory Cascades a. Tc: anhydrotetracycline

Inhibitory Cascades a. Tc: anhydrotetracycline

Longer Transcriptional Cascades Have Increased Steady-State Sensitivity n n Confirms previous theoretical studies Sharper

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

Response Times n n Increase with cascade length Increases length of time before circuit

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

Cell–Cell Variability n n Cell-cell variability increases with longer cascades Noise in transition region

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

Synchronization of Cell Responses n n Hardly any variation in Circuit 1 Peak in

Synchronization of Cell Responses n n Hardly any variation in Circuit 1 Peak in variation during signal transduction in Circuit 3

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

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

Matching kinetic rates n n Need to match kinetic rates of enzymes to output

Matching kinetic rates n n 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

Effects in nature n n n Division Stochastic Nature of reactions Small number of

Effects in nature n n n Division Stochastic Nature of reactions Small number of molecules / longer cascades

Questions & Answers

Questions & Answers

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