Research Spotlight Archive, A Tool-Chain to Accelerate Synthetic Biological Engineering (TASBE)
Participants: Boston University – Swapnil Bhatia (Post Doc), Traci Haddock (Post Doc), and Professor Douglas Densmore (PI)
BBN Technologies – Aaron Adler, Jake Beal, Joe Loyall, Rick Schantz, and Fusun Yaman
MIT – Professor Ron Weiss (PI), Jonathan Babb, and Noah Davidsohn
Funding: Defense Advanced Research Projects Agency (DARPA)
Background: Synthetic biology is at a stage similar to that of computer science in the 1950s: The foundational pieces are starting to emerge, in the form of standardized DNA parts, packaged for combinatoric assembly using standards such as BioBricks. However, creating new DNA parts is tedious and time-consuming, and constructing systems from sets of DNA parts is an ad hoc, manual process that limits the size, complexity, and capability of the resulting systems. The time is right for a research program to develop a tool-chain for the automation of biological design. Such a tool-chain – including higher level abstractions, languages, design patterns, and low-level tool support – would enable the rapid design and development of engineered biological systems with the sophisticated capabilities and large number of constituents, necessary for achieving operational impact. It is vital to begin investigating these problems now, while the processes of biological design are emerging. This will allow the biological building blocks, and the tools for organizing them into systems, to evolve together, accelerating us toward a Moore’s law-style takeoff in both accessibility and complexity of engineered biological systems.
Description: The goal of this starter project is to demonstrate how to apply information system ideas to synthetic biology in order to automate the process of engineering organisms. Specifically, we propose a tool-chain that stretches from a biologically-focused, high-level programming language all the way to realization in cells. The tool-chain will employ programming abstractions and compilation techniques specifically suitable for biological systems, in a similar manner to the use of compiler and optimization algorithms developed for electronic computers and automated integrated circuit design: A biological system designer would begin by expressing desired system function using a biologically-focused high-level programming language. The tool-chain transforms this design systematically into an abstract genetic regulatory network, optimizing to conserve scarce biological resources. This design would then be verified via simulations. Next, abstract parts are mapped onto existing DNA parts (or the need for new parts is revealed) that are assembled in cells using standard protocols and laboratory automation devices. Finally, the cellular implementation will be evaluated experimentally.
Results: This project is just starting, but the images below can help demonstrate how we hope to achieve the results.