Hacking the cell
example, could be engineered, requiring two simultaneous triggers for the expression of two separate genes that then bind together in order to activate the promoter of another target gene. 7
Some projects have produced particularly advanced circuitry, such as Friedland et al. at Boston University, who in 2009 created a synthetic cellular counter – a circuit that could retain memory of up to 3 ‘ arabinose [a pentose] pulses ’ , expressing each possible number of pulses as one of three different proteins. 8 Perhaps the most advanced project yet, however, was published by Tabor et al. at the University of California, in the same year. 9 They were able to engineer an edge-detection algorithm, such as those found in photo-editing software, through a community of genetically engineered E.coli that were able to detect light and dark regions of a projected shape of light. Bacteria that detected a dark region produced a chemical that diffused into nearby cells (but did not respond to the chemical), but bacteria that detected a light region did not produce the chemical but were able to respond to the chemical if it was sensed (which would suggest that these bacteria were on the boundary of light and dark), producing an output identifying their location as an edge. Looking to the future, SBCs have essentially limitless potential applications, impeded only by the rate at which the technology develops. Some of the most exciting applications could be found in healthcare, where the ability to control human cells in any way could lead to the prevention and treatment of countless diseases and conditions. This is best demonstrated by an example, such as opioid overdoses, which killed over 110,000 people in 2017. 10 Opioids, such as morphine, fentanyl, heroin, or methadone, agonize g-protein coupled opioid receptors throughout the body. At high doses, opioids cause respiratory depression through activating mu-opioid receptors in the brainstem, 11 notably in the Pre- Bötzinger complex of the medulla, which is an essential generator of respiratory rhythm in mammals. 12 However, with synthetic biological technology, a circuit could be constructed that would 1. contain a gene that is translated into a mu-opioid receptor antagonist, or an operon that is translated into a series of enzymes that synthesize a mu-opioid receptor antagonist; 2. alternatively, contain a gene that is translated into an extracellular biomarker such as a hormone that could be detected by an electronic device; 3. detect intraneuronal markers of opioid interaction, such as the decrease in positive ions that causes hyperpolarization, or a decrease in cAMP levels; 13 Figure 3 A simplified diagram explaining the E.coli edge-detection algorithm – the bacteria are exposed to a shape of light, invert the light/dark signal, and communicate to establish the light/dark boundary
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