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MIT Open Access Articles Automatic Compilation from High-Level Biologically-Oriented Programming Language to Genetic Regulatory Networks

TLDR
Proto as discussed by the authors is a high-level biologically-oriented programming language for the automated design of complex biological systems, bridging the gap between DNA synthesis and circuit design capabilities, which has been shown to yield significant reductions in the number of genes and latency of the optimized engineered gene networks.
Abstract
Background: The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry. Methodology/PrincipalFindings: To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes ( * 50% ) and latency of the optimized engineered gene networks. Conclusions/Significance: Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems.

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Journal ArticleDOI

Exact Stochastic Simulation of Coupled Chemical Reactions

TL;DR: In this article, a simulation algorithm for the stochastic formulation of chemical kinetics is proposed, which uses a rigorously derived Monte Carlo procedure to numerically simulate the time evolution of a given chemical system.
Journal ArticleDOI

A synthetic oscillatory network of transcriptional regulators

TL;DR: This work used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli, which periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells.
Journal ArticleDOI

Construction of a genetic toggle switch in Escherichia coli

TL;DR: The construction of a genetic toggle switch is presented—a synthetic, bistable gene-regulatory network—in Escherichia coli and a simple theory is provided that predicts the conditions necessary for bistability.
BookDOI

An introduction to systems biology : design principles of biological circuits

Uri Alon
TL;DR: The Robustness Principle can Distinguish Between Mechanisms of Fruit Fly Patterning and Kinetic Proofreading of the Genetic Code can reduce Error Rates of Molecular Recognition Recognition recognition.
Journal ArticleDOI

Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome

TL;DR: The design, synthesis, and assembly of the 1.08–mega–base pair Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a M. capricolum recipient cell to create new cells that are controlled only by the synthetic chromosome are reported.