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A Genetic Differential Amplifier: Design, Simulation, Construction
and Testing
Seema Nagaraj and Stephen Davies
University of Toronto
Edward S. Rogers Sr. Department of Electrical and Computer Engineering
Institute of Biomaterials and Biomedical Engineering
Engineered Genetic Circuits
• artificial networks of interacting DNA, mRNA and proteins
• behavior is analogous to electrical devices
Genetic Differential Amplifier
• differential amplifiers are fundamental components in many electronic circuits
• a genetic differential amplifier could be a building block for more complex genetic circuits
Stochastic Modeling
• includes inputs and output• system behaviour is described through
reaction probabilities• system behaviour is simulated using the
Gillespie algorithm
• Construct HIGH and LOW copy number variants of the circuit
• Compare performance to simulated results
Experimental Results
Experimental ResultsHigh Copy Number
15000
16000
17000
18000
19000
20000
21000
22000
23000
0uM IPTG 2uM IPTG 20uM IPTG 200uM IPTG
10 ng/mL aTc
5 ng/mL aTc
0 ng/mL aTc
Experimental ResultsLow Copy Number
7000
7500
8000
8500
9000
9500
0 uM 2 uM 20 uM 200 uM
10 ng/mL
0 ng/mL
Conclusions
Simulation:• low copy number amplifier based on double-
mutant PRM yields “ideal” behaviour
Experimental:• high copy number amplifier displays
differential amplifier behaviour• low copy number amplifier displays positive
results