Dynamic characterization of synthetic genetic circuits in living cells

A system for determining an intrinsic property of a DNA component involved in transcription of a target signal, the system comprising:

• a processor;
• and
• a memory comprising computer-executable instructions that, when executed by the processor, cause the processor to perform the following operations:
• accessing a plurality of measurements obtained over a time period from a cell culture, wherein each cell in the cell culture comprises the DNA component, and wherein the plurality of measurements comprises a first measurement relating to an amount of the target signal in the cell culture over the time period and a second measurement relating to a density of the cell culture of the time period;
• estimating parameters quantifying the intrinsic property of the DNA component by:
• embedding the estimated parameters within a mathematical model that describes a production of the target signal over the time period;
• and
• minimizing a measure of a difference between outputs of the mathematical model and the first measurement;
• estimating parameter values for a second mathematical model that describes cell culture density over time by minimizing a measure of a difference between an output of the second mathematical model and the second measurement;
• and
• based on the estimated parameters and the estimated parameter values, identifying the intrinsic property.

A computer-readable storage device comprising computer-executable instructions for determining an intrinsic property of a DNA component involved in transcription of a target signal, the computer-executable instructions when executed by a processor, cause the processor to perform the following operations:

• accessing a plurality of measurements obtained over a time period from a cell culture, wherein each cell in the cell culture comprises the DNA component, and wherein the plurality of measurements comprises a first measurement relating to an amount of the target signal in the cell culture over the time period and a second measurement relating to a density of the cell culture of the time period;
• estimating parameters quantifying the intrinsic property of the DNA component by:
• embedding the estimated parameters within a mathematical model that describes a production of the target signal over the time period;
• and
• minimizing a measure of a difference between outputs of the mathematical model and the first measurement;
• estimating parameter values for a second mathematical model that describes cell culture density over time by minimizing a measure of a difference between an output of the second mathematical model and the second measurement;
• and
• based on the estimated parameters and the estimated parameter values, identifying the intrinsic property.