110 likes | 207 Views
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
E N D
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 • Synchroniation/Cell-cell variability
Inhibitory Cascades aTc: anhydrotetracycline
Longer Transcriptional Cascades Have Increased Steady-State Sensitivity • Confirms previous theoretical studies • Sharper steady state transfer in longer cascades
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.
Cell–Cell Variability • Cell-cell variability increases with longer cascades • Noise in transition region is amplified as cascade becomes longer
Synchronization of Cell Responses • Hardly any variation in Circuit 1 • Peak in variation during signal transduction in Circuit 3
Low-Pass Filters 5min. 45min. 60min.
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
Effects in nature • Division • Stochastic Nature of reactions • Small number of molecules / longer cascades