CAGEN: Robust Gene Response Challenge

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WARNING: THIS COMPETITION PROPOSAL IS STILL IN DRAFT FORM This CAGEN challenge problem is still considered in draft form and may be revised. This banner will be removed when challenge has been finalized and selected by the CAGEN steering committee. For more information, see the CAGEN home page.

Synopsis: The goal of this challenge is to design a circuit that can express a fluorescent protein at a controlled level upon the introduction of a chemical inducer, with minimal variation in expression between cells and in multiple contexts. At conditions yielding maximum expression, the circuit should quickly bring the volume-normalized fluorescence from 1X to 10X in response to the addition of an inducer of the designer's choice. The circuit must work at multiple temperatures, with minimal variation in the fluorescence over time, operating temperature and cell choice.

Motivation: Current synthetic circuits demonstrate large variability in expression level when operating different contexts and this limits the ability of synthetic biologists to build on designs performed by other groups. By designing circuits that demonstrate highly repeatable performance over a range of operating conditions, it will be possible to make better use of designs in a modular fashion.

Impact: Improved understanding engineering processes for synthetic biologists will enable more rapid and pervasive development of synthetic circuits, with applications in materials processing, environmental science, agriculture and and medicine.

Metric(s): The winner of this challenge will be determined based on the worst case, mean square error between the ideal step response and the experimental results, with evaluation over multiple temperatures. To be considered, data for the circuit must be submitted for steady state operating temperatures at a nominal value (chosen by the contestant), nominal + 5% and nominal - 5%, with measurements taken in at least 5 individual cells chosen from separate colonies. This represents a set of 15 total time traces of data. At least one of these responses must demonstrate a step response that goes from 1X to 10X expression level in response to the addition of the inducer.

The following method will be used to determine the numerical score for each time response: let [math]\displaystyle{ r_i(t) }[/math] represents the (single) ideal step response at a given induction level i (with minimum and maximum values chosen by the participant), [math]\displaystyle{ y_i(t) }[/math] represents the measured fluorescence of a given cell, T1 represents the time at y(t) reaches 5% of its maximum value and T2 represents that point at which it reaches 95%. Each run will be scored according to the formula:

Score[run] = [math]\displaystyle{ \int_{T1}^{T2} |y_i(t) - r_i(t)|^2 dt }[/math]

The score for the submitted design will be the worst (highest) value of the score across all runs (15 total). Note that [math]\displaystyle{ r_i(t) }[/math] is fixed based on induction level, while [math]\displaystyle{ y_i(t) }[/math] depends on the specific run. The participant can specify a single minimum value for [math]\displaystyle{ r_i(t) }[/math] and a table of maximum values (one for each induction level).

Contact: To provide feedback on this challenge, send e-mail to Richard Murray (murray-at-caltech-dot-edu), representing the steering committee.