Abstract
Gene circuit motifs are structural patterns associated with specific functions. In genetic networks, motifs are made of a small number of transcription units. A single transcription unit that contains a regulated promoter is sufficient to have either a negative or a positive feedback loop. Although very simple, they carry out important tasks such as speed up or slow down the circuit response time, achieve homeostatis (see Chap. 10 ) or obtain bistability (see Chap. 6). The latter is an essential feature to build genetic memory devices. Like these feedback loops, most of the motifs presented in this chapter are based on transcription regulation. Logic operations (Boolean gates) can be carried out by controlling translation as well, either with structures such as riboswitches and ribozymes or via RNA interference (see Chap. 8). We considered as motifs also cell consortia. They are populations of cells where a given function emerges from the interactions of sets of cells devoted to different tasks. As we will see, digital circuits have been engineered as S. cerevisiae cell consortia, where some cells sense the inputs and other perform the logic operation and express a fluorescent output. Finally, we included among circuit motifs re-engineered pathways too. We will show that natural signaling pathways have been modified, both in eukaryotic and bacterial cells, to either respond to an input or express an output different from the original one. Complex circuits can potentially arise by the composition of all these basic motifs.
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Notes
- 1.
Yellow triangles in Fig. 12.1d are bifurcation points where a stable and an unstable steady state coexist. Green triangles, in contrast, are stable steady states.
- 2.
From the herpes simplex virus.
- 3.
Hrp stands for hypersensitive response and pathogenicity.
- 4.
It contains the σ 54 domain.
- 5.
This means that theophylline cannot bind the ribozyme in the absence of tetracycline.
- 6.
A buffer gate was realized according to scheme 3 by using two aptamers bound by theophylline. This YES gate showed moderate cooperativity effects (Hill coefficient: n = 1.65).
- 7.
A destabilized version of the GFP (shorter half-life) was used in [8].
- 8.
The gain, G, of a pulse signal is defined as: \(G=\frac {MAX-E}{E}\), where MAX is the value of the pulse peak and E that of the steady state.
- 9.
μ = aλ, where a < 1.
- 10.
GFP expression is controlled by Fus1 promoter, a component of the yeast mating pathway (see Sect. 12.3).
- 11.
- 12.
\(c^{'}(t)=d c(t)/dt\); \(c^{''}(t)=d^2 c(t)/dt^2\) etc.
- 13.
A kinase is a protein that phosphorylates another protein.
- 14.
MAP: mitogen-activated protein.
- 15.
We term Ste50-zipper and Msg5-zipper the chimeric proteins where a modulator is fused to a leucine zipper heterodimerization module.
- 16.
In this circuit, the Ste50 and Msg5 were not fused to the same leucine zipper heterodimerization module. The module bound to Msg5 conferred to the negative modulator a higher affinity to the synthetic Ste5-zipper.
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Marchisio, M.A. (2018). Circuit Motifs. In: Introduction to Synthetic Biology. Learning Materials in Biosciences. Springer, Singapore. https://doi.org/10.1007/978-981-10-8752-3_12
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DOI: https://doi.org/10.1007/978-981-10-8752-3_12
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