Control of synthetic gene networks and its applications

Menn, David J.; Su, Ri Qi; Wang, Xiao

doi:10.1007/s40484-017-0106-5

Cited by 2 publications

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References 114 publications

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“…Studying fundamental genetic motifs in isolation has yielded a greater understanding of key cellular behaviors, such as multistability, oscillation, and adaptation. − Multistable networks, specifically, are highly relevant for cellular differentiation processes and have wide applicability in a diverse range of contexts, from developmental biology to targeted therapeutics and cell-environment interactions . Synthetic toggle switches have been implemented repeatedly in multiple organisms, demonstrating the feasibility of studying differentiation with minimal, synthetic circuits. ,,, Further exploration of bistable circuits can reveal mechanisms of subpopulation control and manipulation, limitations of diverse control schema, and best practices for state transition control on single cell and population levels. , For example, recent work has studied how circuit component selection affects the network’s hysteretic region and how inclusion of additional circuit components can be used to adjust population ratios …”

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confidence: 99%

“…23,25,32,33 Further exploration of bistable circuits can reveal mechanisms of subpopulation control and manipulation, limitations of diverse control schema, and best practices for state transition control on single cell and population levels. 34,35 For example, recent work has studied how circuit component selection affects the network's hysteretic region 25 inclusion of additional circuit components can be used to adjust population ratios. 36 Here, we present methods for reliably tuning a multimodal population's ratios without the need for additional network components.…”

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confidence: 99%

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Intracellular Noise Level Determines Ratio Control Strategy Confined by Speed–Accuracy Trade-off

et al. 2019

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Robust and precise ratio control of heterogeneous phenotypes within an isogenic population is an essential task, especially in the development and differentiation of a large number of cells such as bacteria, sensory receptors, and blood cells. However, the mechanisms of such ratio control are poorly understood. Here, we employ experimental and mathematical techniques to understand the combined effects of signal induction and gene expression stochasticity on phenotypic multimodality. We identify two strategies to control phenotypic ratios from an initially homogeneous population, suitable roughly to high-noise and low-noise intracellular environments, and we show that both can be used to generate precise fractional differentiation. In noisy gene expression contexts, such as those found in bacteria, induction within the circuit's bistable region is enough to cause noise-induced bimodality within a feasible time frame. However, in less noisy contexts, such as tightly controlled eukaryotic systems, spontaneous state transitions are rare and hence bimodality needs to be induced with a controlled pulse of induction that falls outside the bistable region. Finally, we show that noise levels, system response time, and ratio tuning accuracy impose trade-offs and limitations on both ratio control strategies, which guide the selection of strategy alternatives.

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