Biomedically relevant circuit‐design strategies in mammalian synthetic biology

AbstractSpatial organisation through localisation/compartmentalisation of species is a ubiquitous but poorly understood feature of cellular biomolecular networks. Current technologies in systems and synthetic biology (spatial proteomics, imaging, synthetic compartmentalisation) necessitate a systematic approach to elucidating the interplay of networks and spatial organisation. We develop a systems framework towards this end and focus on the effect of spatial localisation of network components revealing its multiple facets: (i) As a key distinct regulator of network behaviour, and an enabler of new network capabilities (ii) As a potent new regulator of pattern formation and self-organisation (iii) As an often hidden factor impacting inference of temporal networks from data (iv) As an engineering tool for rewiring networks and network/circuit design. These insights, transparently arising from the most basic considerations of networks and spatial organisation, have broad relevance in natural and engineered biology and in related areas such as cell-free systems, systems chemistry and bionanotechnology.

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Mathematical Modeling: Bridging the Gap between Concept and Realization in Synthetic Biology

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/541609 ◽

2010 ◽

Vol 2010 ◽

pp. 1-16 ◽

Cited By ~ 20

Author(s):

Yuting Zheng ◽

Ganesh Sriram

Keyword(s):

Mathematical Modeling ◽

Synthetic Biology ◽

Circuit Design ◽

Central Component ◽

Transcription Network ◽

Phenotype Analysis ◽

Synthetic Circuit ◽

Gene Regulatory ◽

Mathematical Techniques

Mathematical modeling plays an important and often indispensable role in synthetic biology because it serves as a crucial link between the concept and realization of a biological circuit. We review mathematical modeling concepts and methodologies as relevant to synthetic biology, including assumptions that underlie a model, types of modeling frameworks (deterministic and stochastic), and the importance of parameter estimation and optimization in modeling. Additionally we expound mathematical techniques used to analyze a model such as sensitivity analysis and bifurcation analysis, which enable the identification of the conditions that cause a synthetic circuit to behave in a desired manner. We also discuss the role of modeling in phenotype analysis such as metabolic and transcription network analysis and point out some available modeling standards and software. Following this, we present three case studies—a metabolic oscillator, a synthetic counter, and a bottom-up gene regulatory network—which have incorporated mathematical modeling as a central component of synthetic circuit design.

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Optimization-Based Eukaryotic Genetic Circuit Design (EuGeneCiD) and Modeling (EuGeneCiM) Tools: Computational Approach to Synthetic Biology

SSRN Electronic Journal ◽

10.2139/ssrn.3850370 ◽

2021 ◽

Author(s):

Wheaton L. Schroeder ◽

Anna S. Baber ◽

Rajib Saha

Keyword(s):

Synthetic Biology ◽

Circuit Design ◽

Computational Approach ◽

Genetic Circuit

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What Is the Role of Circuit Design in the Advancement of Synthetic Biology? Part 2

Cell Systems ◽

10.1016/j.cels.2017.05.006 ◽

2017 ◽

Vol 4 (5) ◽

pp. 476-477

Keyword(s):

Synthetic Biology ◽

Circuit Design

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What Is the Role of Circuit Design in the Advancement of Synthetic Biology? Part 1

Cell Systems ◽

10.1016/j.cels.2017.04.003 ◽

2017 ◽

Vol 4 (4) ◽

pp. 370-372

Keyword(s):

Synthetic Biology ◽

Circuit Design

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Emerging Species and Genome Editing Tools: Future Prospects in Cyanobacterial Synthetic Biology

Microorganisms ◽

10.3390/microorganisms7100409 ◽

2019 ◽

Vol 7 (10) ◽

pp. 409 ◽

Cited By ~ 7

Author(s):

Grant A. R. Gale ◽

Alejandra A. Schiavon Osorio ◽

Lauren A. Mills ◽

Baojun Wang ◽

David J. Lea-Smith ◽

...

Keyword(s):

Synthetic Biology ◽

Circuit Design ◽

Applied Research ◽

Genetic Circuit ◽

Small Subset ◽

Molecular Tools ◽

Model Species ◽

New Techniques ◽

Algal Biotechnology ◽

Potential Applications

Recent advances in synthetic biology and an emerging algal biotechnology market have spurred a prolific increase in the availability of molecular tools for cyanobacterial research. Nevertheless, work to date has focused primarily on only a small subset of model species, which arguably limits fundamental discovery and applied research towards wider commercialisation. Here, we review the requirements for uptake of new strains, including several recently characterised fast-growing species and promising non-model species. Furthermore, we discuss the potential applications of new techniques available for transformation, genetic engineering and regulation, including an up-to-date appraisal of current Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein (CRISPR/Cas) and CRISPR interference (CRISPRi) research in cyanobacteria. We also provide an overview of several exciting molecular tools that could be ported to cyanobacteria for more advanced metabolic engineering approaches (e.g., genetic circuit design). Lastly, we introduce a forthcoming mutant library for the model species Synechocystis sp. PCC 6803 that promises to provide a further powerful resource for the cyanobacterial research community.

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Synthetic Biology on Acetogenic Bacteria for Highly Efficient Conversion of C1 Gases to Biochemicals

International Journal of Molecular Sciences ◽

10.3390/ijms21207639 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7639

Author(s):

Sangrak Jin ◽

Jiyun Bae ◽

Yoseb Song ◽

Nicole Pearcy ◽

Jongoh Shin ◽

...

Keyword(s):

Carbon Dioxide ◽

Carbon Monoxide ◽

Synthetic Biology ◽

Circuit Design ◽

Metabolic Pathways ◽

Fossil Fuels ◽

Slow Growth ◽

Value Added ◽

Biomass Gasification ◽

Acetogenic Bacteria

Synthesis gas, which is mainly produced from fossil fuels or biomass gasification, consists of C1 gases such as carbon monoxide, carbon dioxide, and methane as well as hydrogen. Acetogenic bacteria (acetogens) have emerged as an alternative solution to recycle C1 gases by converting them into value-added biochemicals using the Wood-Ljungdahl pathway. Despite the advantage of utilizing acetogens as biocatalysts, it is difficult to develop industrial-scale bioprocesses because of their slow growth rates and low productivities. To solve these problems, conventional approaches to metabolic engineering have been applied; however, there are several limitations owing to the lack of required genetic bioparts for regulating their metabolic pathways. Recently, synthetic biology based on genetic parts, modules, and circuit design has been actively exploited to overcome the limitations in acetogen engineering. This review covers synthetic biology applications to design and build industrial platform acetogens.

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