scholarly journals Multiplexed Gene Expression Tuning with Orthogonal Synthetic Gene Circuits

2020 ◽  
Vol 9 (4) ◽  
pp. 930-939 ◽  
Author(s):  
Mariola Szenk ◽  
Terrence Yim ◽  
Gábor Balázsi
Keyword(s):  
Gene Expression ◽  
Synthetic Gene ◽  
Gene Circuits ◽  
Synthetic Gene Circuits

scholarly journals Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits

2020 ◽  
Author(s):  
Lei Wei ◽  
Shuailin Li ◽  
Tao Hu ◽  
Michael Q. Zhang ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Types ◽  
Classification Performance ◽  
Synthetic Gene ◽  
Gene Circuits ◽  
Gene Expression Noise ◽  
Expression Noise ◽  
Synthetic Gene Circuits ◽  
Highly Expressed Genes ◽  
Lower Noise

AbstractGene expression noise plays an important role in many biological processes, such as cell differentiation and reprogramming. It can also dramatically influence the behavior of synthetic gene circuits. MicroRNAs (miRNAs) have been shown to reduce the noise of lowly expressed genes and increase the noise of highly expressed genes, but less is known about how miRNAs with different properties may regulate gene expression noise differently. Here, by quantifying gene expression noise using mathematical modeling and experimental measurements, we showed that competing RNAs and the composition of miRNA response elements (MREs) play important roles in modulating gene expression noise. We found that genes targeted by miRNAs with weak competing RNAs show lower noise than those targeted by miRNAs with strong competing RNAs. In addition, in comparison with a single MRE, repetitive MREs targeted by the same miRNA suppress the noise of lowly expressed genes but increase the noise of highly expressed genes. Additionally, MREs composed of different miRNA targets could cause similar repression levels but lower noise compared with repetitive MREs. We further observed the influence of miRNA-mediated noise modulation in synthetic gene circuits which could be applied to classify cell types using miRNAs as sensors. We found that miRNA sensors that introduce higher noise could lead to better classification performance. Our results provide a systematic and quantitative understanding of the function of miRNAs in controlling gene expression noise and how we can utilize miRNAs to modulate the behavior of synthetic gene circuits.

scholarly journals Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits

Cell Reports ◽  
2021 ◽  
Vol 36 (8) ◽  
pp. 109573
Author(s):  
Lei Wei ◽  
Shuailin Li ◽  
Pengcheng Zhang ◽  
Tao Hu ◽  
Michael Q. Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synthetic Gene ◽  
Gene Circuits ◽  
Gene Expression Noise ◽  
Expression Noise ◽  
Synthetic Gene Circuits ◽  
Modulation Of Gene Expression

scholarly journals Growth defects and loss-of-function in synthetic gene circuits

2019 ◽  
Author(s):  
Evangelos-Marios Nikolados ◽  
Andrea Y. Weiße ◽  
Francesca Ceroni ◽  
Diego A. Oyarzún
Keyword(s):  
Gene Expression ◽  
Logic Gates ◽  
Synthetic Gene ◽  
Loss Of Function ◽  
Gene Circuits ◽  
Bacterial Gene ◽  
Growth Defects ◽  
Synthetic Gene Circuits ◽  
Cellular Capacity ◽  
The Impact

AbstractSynthetic gene circuits perturb the physiology of their cellular host. The extra load on endogenous processes shifts the equilibrium of resource allocation in the host, leading to slow growth and reduced biosynthesis. Here we built integrated host-circuit models to quantify growth defects caused by synthetic gene circuits. Simulations reveal a complex relation between circuit output and cellular capacity for gene expression. For weak induction of heterologous genes, protein output can be increased at the expense of growth defects. Yet for stronger induction, cellular capacity reaches a tipping point, beyond which both gene expression and growth rate drop sharply. Extensive simulations across various growth conditions and large regions of the design space suggest that the critical capacity is a result of ribosomal scarcity. We studied the impact of growth defects on various gene circuits and transcriptional logic gates, which highlights the extent to which cellular burden can limit, shape and even break down circuit function. Our approach offers a comprehensive framework to assess the impact of host-circuit interactions in silico, with wide-ranging implications for the design and optimization of bacterial gene circuits.

Synthetic Gene Circuits: Design, Implement, and Apply

2021 ◽  
pp. 1-18
Author(s):  
Andrew Lezia ◽  
Arianna Miano ◽  
Jeff Hasty
Keyword(s):  
Synthetic Gene ◽  
Gene Circuits ◽  
Synthetic Gene Circuits

Synthetic Gene Circuits

2014 ◽  
pp. 1-56 ◽  
Author(s):  
Barbara Jusiak ◽  
Ramiz Daniel ◽  
Fahim Farzadfard ◽  
Lior Nissim ◽  
Oliver Purcell ◽  
...  
Keyword(s):  
Synthetic Gene ◽  
Gene Circuits ◽  
Synthetic Gene Circuits

scholarly journals Two cellular resource‐based models linking growth and parts characteristics aids the study and optimisation of synthetic gene circuits

2017 ◽  
Vol 1 (1) ◽  
pp. 30-39 ◽  
Author(s):  
Huijuan Wang ◽  
Maurice H.T. Ling ◽  
Tze Kwang Chua ◽  
Chueh Loo Poh
Keyword(s):  
Synthetic Gene ◽  
Gene Circuits ◽  
Synthetic Gene Circuits
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