CAGEN: Robust Synthetic Development 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 with specific self‐generated spatial patterns. These patterns should ideally emerge without external spatial cues. The two basic patterns we consider are: (1) A circular pattern with a diameter of exactly N cells, where cell are on at the center of the circle and off outside (2) A striped on‐off pattern with a wavelength of exactly N cell diameters. The boundaries formed should exhibit a sharp turn‐on and turn‐off functions on the order of one cell length with minimal errors (no off cells in the on area and vice versa).

Synthetic developmental patterning challenge. The ideal circular (left) and striped (right) patterns for this challenge. Boundaries for challenge #2 may be determined by external restriction of growth region.

Motivation: Motivation for this challenge is twofold: (1) Current synthetic circuits are limited in their ability to form self emerging spatial patterns in a robust manner. In fact, most current synthetic patterning circuits are driven by external cues. This challenge will likely push forward the technology for developing synthetic circuits based on cell‐cell communication (2) By constructing synthetic circuits exhibiting robust self emerging spatial patterns we can learn about the mechanisms involved in developmental patterning circuits. In particular, such a challenge would help explore the range of possible genetic circuits that can generate multicellular development and their limitations.

Impact: The impact of this challenge is twofold: (1) Improved understanding of basic engineering principles for synthetic biologists will enable more rapid and pervasive development of synthetic circuits, with applications in materials processing, environmental science, agriculture and medicine. (2) The ability to generate self emerging spatial patterns may be important in the field of tissue engineering where precise and accurate patterns of differentiation are required.

Metric(s): The winner of this challenge will be determined based on the difference between the observed mean spatial response function and an ideal spatial pattern. The ideal pattern for the concentric ring challenge ( #1) is on at a diameter of N (TBD) cells and turns off sharply at beyond that diameter. The ideal pattern for striped pattern challenge (#2) is an on and off patterns with a fixed wavelength of N (TBD) cells. Again, boundaries between on and off states should be sharp.

The following method will be used to determine the numerical score for each submission: let [math]\displaystyle{ r_i(x) }[/math] represent the ideal spatial response curve (for the concentric ring: Fmax for R<RN, 0 for R>RN, where RN represent the diameter of N cells, and Fmax is a maximal fluorescence level (determined by contestant)). Let [math]\displaystyle{ y_i(x) }[/math] represent the measured fluorescence of a given cell at steady state (time will be determined by contestant). Each run will be scored according to the formula:

Score[run] = [math]\displaystyle{ \int_0^\infty |y_i(x) - r_i(x)|^2 dx }[/math]

A similar scoring method will be applied to the striped pattern.

The score for the submitted design will be the worst (highest) value of the score across 3 runs each at 3 temperatures: nominal, nominal-5%, nominal+5% (where nominal is chosen by the contestant). Final determination of the winner will be done by a jury consisting of the CAGEN steering committee.

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