scholarly journals Growth Defects and Loss-of-Function in Synthetic Gene Circuits

2019 ◽  
Vol 8 (6) ◽  
pp. 1231-1240 ◽  
Author(s):  
Evangelos-Marios Nikolados ◽  
Andrea Y. Weiße ◽  
Francesca Ceroni ◽  
Diego A. Oyarzún
Keyword(s):  
Synthetic Gene ◽  
Loss Of Function ◽  
Gene Circuits ◽  
Growth Defects ◽  
Synthetic Gene Circuits

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

scholarly journals Multistable and dynamic CRISPRi-based synthetic circuits

2019 ◽  
Author(s):  
Javier Santos-Moreno ◽  
Eve Tasiudi ◽  
Joerg Stelling ◽  
Yolanda Schaerli
Keyword(s):  
Context Dependency ◽  
Synthetic Gene ◽  
Toggle Switch ◽  
Stripe Pattern ◽  
Gene Circuits ◽  
Synthetic Gene Circuits ◽  
Gene Expression Control ◽  
Unspecific Binding ◽  
High Predictability ◽  
Pattern Forming

AbstractGene expression control based on CRISPRi (clustered regularly interspaced short palindromic repeats interference) has emerged as a powerful tool for creating synthetic gene circuits, both in prokaryotes and in eukaryotes; yet, its lack of cooperativity has been pointed out as a potential obstacle for dynamic or multistable circuit construction. Here we use CRISPRi to build prominent synthetic gene circuits in Escherichia coli. We report the first-ever CRISPRi oscillator (“CRISPRlator”), bistable network (toggle switch) and stripe pattern-forming incoherent feed-forward loop (IFFL). Our circuit designs, conceived to feature high predictability and orthogonality, as well as low metabolic burden and context-dependency, allowed us to achieve robust circuit behaviors. Mathematical modeling suggests that unspecific binding in CRISPRi is essential to establish multistability. Our work demonstrates the wide applicability of CRISPRi in synthetic circuits and paves the way for future efforts towards engineering more complex synthetic networks, boosted by the advantages of CRISPR technology.

scholarly journals Synthetic Gene Circuits for Antimicrobial Resistance and Cancer Research

2021 ◽  
Author(s):  
Kevin S. Farquhar ◽  
Michael Tyler Guinn ◽  
Gábor Balázsi ◽  
Daniel A. Charlebois
Keyword(s):  
Mammalian Cells ◽  
Rational Design ◽  
Study Drug ◽  
Quantitative Model ◽  
Synthetic Gene ◽  
Modeling Tools ◽  
Gene Circuits ◽  
Novel Treatments ◽  
Synthetic Gene Circuits ◽  
Temporal Dimensions

Mathematical models and synthetic gene circuits are powerful tools to develop novel treatments for patients with drug-resistant infections and cancers. Mathematical modeling guides the rational design of synthetic gene circuits. These systems are then assembled into unified constructs from existing and/or modified genetic components from a range of organisms. In this chapter, we describe modeling tools for the design and characterization of chemical- and light-inducible synthetic gene circuits in different organisms and highlight how synthetic gene circuits are advancing biomedical research. Specifically, we demonstrate how these quantitative model systems are being used to study drug resistance in microbes and to probe the spatial–temporal dimensions of cancer in mammalian cells.

Sign in / Sign up

Export Citation Format

Share Document