Abstract
BackgroundThe 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/Principal FindingsTo 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 () and latency of the optimized engineered gene networks.Conclusions/SignificanceOur 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.
Highlights
Synthetic biology is an emerging field at the interface of biology, engineering, and physical sciences, which focuses on the systematic design and engineering of biological systems [1,2,3]
Building upon early studies such as an engineered genetic toggle switch [4] and an oscillator [5], synthetic biology efforts have created a large collection of functional devices and small regulatory modules that use a variety of biochemical processes
We present a platform that allows synthetic biologists to design biological systems using the Proto high-level biologically-oriented programming language
Summary
Synthetic biology is an emerging field at the interface of biology, engineering, and physical sciences, which focuses on the systematic design and engineering of biological systems [1,2,3]. Building upon early studies such as an engineered genetic toggle switch [4] and an oscillator [5], synthetic biology efforts have created a large collection of functional devices and small regulatory modules that use a variety of biochemical processes. These efforts include both single cell and multicellular functions, such as logic function evaluators, an edge detector, synchronized oscillator, and spatial pattern generators [6,7,8,9]. DNA synthesis technologies have demonstrated dramatic improvements over the past decade [10] with a recent publication of a functional synthetically synthesized mega-base-pair genome [11]. 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
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