53rd IEEE Conference on Decision and Control 2014
DOI: 10.1109/cdc.2014.7040238
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Limitations and trade-offs in gene expression due to competition for shared cellular resources

Abstract: Abstract-Gene circuits share transcriptional and translational resources in the cell. The fact that these common resources are available only in limited amounts leads to unexpected couplings in protein expressions. As a result, our predictive ability of describing the behavior of gene circuits is limited. In this paper, we consider the simultaneous expression of proteins and describe the coupling among protein concentrations due to competition for RNA polymerase and ribosomes. In particular, we identify the li… Show more

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Cited by 41 publications
(44 citation statements)
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“…As we try to build synthetic gene regulation networks, we need to understand competition for resources giving rise to limitations and tradeoffs. Both mathematical modeling and experimental studies are directed towards elucidation of this issue [17,18,7]. In the system studied, we provide evidence that suppression of gene expression due to added NTP is not primarily due to competition between transcription and translation as has been proposed in [7], but we suggest that the limitation of available free Mg 2+ plays a role in this suppression.…”
Section: +mentioning
confidence: 79%
“…As we try to build synthetic gene regulation networks, we need to understand competition for resources giving rise to limitations and tradeoffs. Both mathematical modeling and experimental studies are directed towards elucidation of this issue [17,18,7]. In the system studied, we provide evidence that suppression of gene expression due to added NTP is not primarily due to competition between transcription and translation as has been proposed in [7], but we suggest that the limitation of available free Mg 2+ plays a role in this suppression.…”
Section: +mentioning
confidence: 79%
“…Excessive gene overexpression may cause imbalance in gene dosage, affecting protein synthesis, folding, and localization, assembly of multiprotein complexes, and the machinery of gene regulation. Flooding the cell with recombinant proteins may lead to excessive consumption of cellular resources, affecting cell growth rate and metabolism [18]. While these aspects are often overlooked, they represent serious concerns in view of a wider applicability and clinical translation of overexpression-based strategies.…”
Section: Introductionmentioning
confidence: 99%
“…Yeung et al illustrate, using tools from dynamical systems, that resource sharing leads to non-minimum phase zeros in the transfer function of a linearized genetic cascade circuit [6]. Gyorgy et al develop the notion of realizable region for steady state gene expression under resource limitations [7]. Hamadeh et al analyze and compare different feedback architectures to mitigate resource competition [8].…”
Section: Introductionmentioning
confidence: 99%