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IDR Team Summary 5: Why are human-designed biological circuits and devices fragile and inaccurate relative to their natural counterparts?
Pages 45-52

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From page 45...
... constructed an oscillator based on a transcriptional cascade and found that only a fraction of cells exhibited oscillations; additionally, they observed significant variation in the period and amplitude between cells in a population. In comparison, the transcriptional oscillations associated with the circadian clock are far more robust.
From page 46...
... In the process of natural selection, a population of cells or organisms effectively explores parameter space in a manner that allows for the discovery of biological circuits that are robust, adaptable and redundant. In contrast, many efforts in synthetic biology are engineering-based and exploit the modular nature of biology to assemble functioning circuits from sets of well-characterized component parts.
From page 47...
... Keck Foundation •  Jeffery Schloss, National Human Genome Research Institute, NIH • Georg Seelig, University of Washington • David Sprinzak, California Institute of Technology • Nancy Sung, Burroughs Wellcome Fund • Stephanie W Schupska, University of Georgia IDR Team Summary By Stephanie W
From page 48...
... iGEM, which stands for International Genetically Engineered Machine, is a biological challenge considered the premier student synthetic biology competition. Source of Fragility Synthetic biology is still in its earliest stages, much like the first bulky transistor compared to the current multi-trillion transistor model of today's Internet.
From page 49...
... one. Wind Tunnel When it comes to making synthesized biological circuits more accurate and less fragile, the IDR team decided a more detailed analysis of the engineering approach is needed.
From page 50...
... A wind tunnel in synthetic biology is still more of a concept than a real testing ground, but researchers are optimistic. A wind tunnel would allow them to develop carefully characterized test environments for measuring the functionality of cell-free extracts, which are liquids that contain cell parts but no intact cells, and minimal cells, which are artificial cells that contain the smallest number of parts a cell needs to exist.
From page 51...
... These could include activators, repressors and combinatorial promoters. Circuits would then be rapidly introduced into mammalian cells, in a way that allows comparisons (for example, control integration loci)
From page 52...
... 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.


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