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break. Part of this approach’s goal is to figure out what the cell’s mechanisms are for breaking the systems that researchers are trying to build. The next step would be to redesign some of the systems and increase their genetic stability.

The failure mode frameworks they suggested involve performance timescales, metabolic load, noise, intrinsic versus extrinsic versus crosstalk failures and dependence on system size.

They suggest four types of experiments to test failure mode:

  • Studies of genetic stability as a function of load.

  • Comparison between analogous natural and synthetic systems.

  • Case-by-case analysis of extrinsic interference.

  • Host optimization to improve robustness.

Grand Challenge

In 2004, the DARPA (Defense Advanced Research Projects Agency) Grand Challenge dared contestants to build a vehicle that could make it across the Mohave Desert. The first year, everyone failed. The second year, five vehicles made it across. The third year, teams were faced with an even more complex problem: To drive an unmanned vehicle 60 miles through an urban area while obeying all traffic signals. The prize was $2 million. Six teams finished.

A biological challenge called iGEM already exists. For the contest, student teams work with a kit of biological parts and new parts they design to build biological systems and operate them in living cells. Unfortunately, the competition doesn’t take aim at robustness, research on which is sorely needed in synthetic biology. The group proposed a contest based on robustness. It could either be incorporated as a part of iGEM or introduced as a new grand challenge.

It would involve, for example, students making an oscillator, placing it in a plasmid and then testing that oscillator in 10 different strains of E. coli and seeing which one works best. The challenge, like the DARPA Challenge, would be fine-tuned from year to year as progress is made.

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