repressilator · 2017. 9. 29. · the repressilator system gene a gene b gene c protein a protein b...
TRANSCRIPT
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RepressilatorBrenton Munson, Jonathan
Pekar, Clara Posner
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Complex Genetic Networks
(Hasty) Welcome to BioInformatics 284. Slide 20.
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Synthetic Biology
© 2014 Macmillan Publishers Limited. All rights reserved
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The Central Dogma of Biology
© 2015 Pearson Education, Inc. PowerPoint Lectures Campbell Biology: Concepts & Connections, Eighth Edition REECE TAYLOR SIMON DICKEY HOGAN Chapter 10.
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Integrated Gene Circuits: The Toggle Switch
Gene A
Protein A
Gene B
Protein B
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The Repressilator System
Gene A Gene B
Gene C
Protein A Protein B
Protein C
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The Repressilator System
Gene A Gene B
Gene C
Protein A Protein B
Protein C
Assumptions● Stable temperature
○ Temperature affects binding and decay rates
● Closed system○ No protein or mRNA
leaving/entering the system
In a single cell
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The Repressilator System: General Form
Rate of Change of the mRNA Concentration
Rate of Change of Protein Concentration
● a: [mRNA a]● A: [protein A]● C: [protein C]
○ represses TX of gene AFollowing parameters same for all species:● kdm: mRNA deg.● α: TX rate● n: Hill’s coefficient ● kdp: protein deg.● β: TL rate
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The Repressilator System: For All 3 GenesRate of Change of the mRNA Concentration
Rate of Change of Protein Concentration
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The Repressilator System: Initial ConditionsInitial mRNA Concentrations
Initial Protein Concentrations
Parameter Values
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Numerical Method - Explicit Runge-Kutta (RK4)
xn xn + hxn + h/2
k1
k3
k2
k4
ϕ
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Repressilator - Starting times
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Repressilator - Steady State
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Modulating Regulated Transcription Rate (α)
Rate of Change of the mRNA Concentration
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Modulating Translation (β)
Rate of Change of Protein Concentration
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Modulating Cooperativity of Repressor and DNA
Rate of Change of the mRNA Concentration
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The Repressilator System with a Drug Inducer
Gene A Gene B
Gene C
Protein A Protein B
Protein C
A single cell
D DAssumptions
● Spike the media (extracellular fluid) with D
○ [D] outside the cell >> [D] inside the cell
○ Diffusion out of cell is negligible
New Parameter● D = drug
○ Can diffuse in and out of the cell
○ Activates gene A
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The Repressilator System with a Drug Inducer
Rate of Change of the mRNA Concentration
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The Repressilator System & Synchronization
Gene A Gene B
Gene C
Protein A Protein B
Protein C
Gene AGene B
Gene C
Protein AProtein B
Protein C
Gene A Gene B
Gene C
Protein A Protein B
Protein C
Cell 1 Cell 2
Cell 3
D
D
D
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The Repressilator: 3 Cell System (i=1,2,3)
mRNA concentrations: a, b, c Protein concentrations: A, B, C & Drug concentration
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The Repressilator: 3 Cell System Initial ConditionsCell 1 Cell 2 Cell 3
A(t=0)=B(t=0)=C(t=0)=0 for all cells
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Repressilator with Sensing - 3 cell synchronization
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Repressilator with Sensing - 3 cell synchronization
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The Repressilator System: Adding Complexity
Gene A Gene B
Gene C
Protein A Protein B
Protein C
A single cell
DD
Gene D
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Extra Slides
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The Effect of Basal Transcription Rate (α0)Rate of Change of the mRNA Concentration
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The Effect of Protein Degradation
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Coupled RK4