A universal control system for synthetic gene networks

Nature | June 19, 2019

Anyone who has lived without central heating and cooling has had to learn the right combinations of opening windows, turning on radiators or adjusting blinds to get the temperature just right. Modern thermostats eliminate all that: you set them once and the built-in controllers do the rest, regardless of changes in the weather or the type of home. The temperature might still vary a little, but as long as the heaters and coolers are designed correctly, it should vary around the set point, rather than merely taking the edge off the cold or heat. Writing in Nature, Aoki and colleagues report1 an analogous system for chemical reactions in living cells. Specifically, they design a reaction module in which two components sequester each other, and show that adding this to almost any network can force the output of the system to maintain a precise value that is proportional to an input signal, in a way that is robust to both external disturbances and uncertainty in the internal parameters — a behaviour known as robust perfect adaptation. The results are striking for two reasons. First, most self-corrective biochemical circuits merely dampen the effects of external changes, rather than compensate for them perfectly. For example, by auto-repressing their own production, proteins can make their abundances less responsive to parameter changes than they would otherwise be, but still respond to some extent (Fig. 1a). Such systems are therefore known as homeostatic regulators because they maintain similar (homeo), rather than the same (homo), protein levels. Second, the impact of adding extra reactions to a biomolecular network usually depends on context. For instance, adding a repression step could create a positive or a negative feedback loop, depending on the rest of the network. Most systems have therefore been modelled and engineered on a case-by-case basis, and it has been hard even to imagine that any universal synthetic control could be found.

Spotlight

The biopharmaceutical industry has grown impressively in recent years, with its global compound growth rate (CAGR) estimated to reach 8.5% between 2018-2023, outstripping traditional New Chemical Entity sectors1 . Emerging novel drugs show huge therapeutic potential, such as antibodydrug conjugates (ADCs), checkpoint inhibitors and viral gene therapy. But as the industry grows, it may face potential issues securing an expanded supply chain.

Spotlight

The biopharmaceutical industry has grown impressively in recent years, with its global compound growth rate (CAGR) estimated to reach 8.5% between 2018-2023, outstripping traditional New Chemical Entity sectors1 . Emerging novel drugs show huge therapeutic potential, such as antibodydrug conjugates (ADCs), checkpoint inhibitors and viral gene therapy. But as the industry grows, it may face potential issues securing an expanded supply chain.

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