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IDR Team Summary 3: Reconstructing gene circuitry: How can synthetic biology lead us to an understanding of the principles underlying natural genetic circuits and to the discovery of new biology?
Pages 25-36

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From page 25...
... How different are potential circuit designs, that we imagine, from the actual circuit designs that have evolved to solve biological problems? Due to an enormous expansion in our knowledge about genetic components and interactions in a number of model systems, we are now in a position to pursue a complementary approach to understanding natural gene circuits, based on reconstruction of genetic circuits.
From page 26...
... Finally, different circuit designs with similar functions can be directly compared to determine the precise properties each design grants a network as well as their relative advantages and disadvantages in particular cellular contexts. Ultimately, these studies may provide us with a deep enough understanding that we can design circuits that perform novel biological functions and we can exploit synthetic circuitry to reveal basic principles about natural circuit design.
From page 27...
... In particular, what can synthetic biology do to better understand probabilistic behaviors, developmental circuits, neural circuits, immune circuits, and plant circuits? • Can we delete natural circuits and replace them with synthetic counterparts within organisms?
From page 28...
... Ninfa, University of Michigan Medical School • Santa J Ono, Emory University • Jeffrey Tabor, University of California, San Francisco • Leor Weinberger, University of California, San Diego • Lingchong You, Duke University • Daniel Strain, University of California, Santa Cruz IDR Team Summary -- Group A By Daniel Strain, Graduate Science Writing Student, University of California, Santa Cruz It's time for biologists to stop worrying about failure.
From page 29...
... The group asked if a "failed" synthetic circuit could help scientists better understand natural circuits and locate missing genes, proteins or chemical reactions. Can failures help untie the knots?
From page 30...
... Synthetic biologists often consider noise a hassle, making finely constructed synthetic circuits fizzle. But such randomness may be critical to cellular function.
From page 31...
... Because the fluorescent markers dim over time, scientists can use them to track the randomness in stem cells as they become part of the fish's tail or slippery skin. The team also proposed assembling a catalogue of instances in which synthetic circuits produce unwanted or unpredictable results called a deviance library.
From page 32...
... The group consisted of a diverse set of physicists, engineers, developmental biologists, computational biologists, biochemists, and chemists. Its stated challenge was to determine how synthetic biology can lead to an understanding of the principles underlying natural genetic circuits and to the discovery of new biology.
From page 33...
... The team also raised the idea that synthetic biology could help determine underlying principles that govern cellular behavior. For instance, if all bacteria that use a gradient of chemicals to sense and move toward food rely on a certain fundamental set of genes, proteins, or chemical signals, synthetic biology might confirm that.
From page 34...
... Synthetic tools may also help scientists detect changes. Tweaking the System At the level of small molecules, biologists need a way to tune precisely the amount of each chemical in specific sites in the cell (such as the nucleus)
From page 35...
... Given the explosion of new technologies that a synthetic tool box would provide, new analytical techniques may help researchers focus their efforts and design experiments more efficiently. When the inputs are more finely controlled, it may also be necessary to determine which of the numerous variables should be measured, and with what resolution.
From page 36...
... While synthetic biology is traditionally touted as a way to create tailormade, artificial biology, its potential for understanding the natural world has not yet been realized. Though a multi-purpose, synthetic biology-based tool as envisioned by the team is still a long ways away, it could ultimately provide a deeper understanding of natural biological systems.


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