Computer assisted design, CAD for RNA, synthetic biology

The computer assisted design (CAD) tools that made it possible to fabricate integrated circuits with millions of transistors may soon be coming to the biological sciences. Researchers at the U.S. Department of Energy (DOE)’s Joint BioEnergy Institute (JBEI) have developed CAD-type models and simulations for RNA molecules that make it possible to engineer biological components or “RNA devices” for controlling genetic expression in microbes. This holds enormous potential for microbial-based sustainable production of advanced biofuels, biodegradable plastics, therapeutic drugs and a host of other goods now derived from petrochemicals.

“Because biological systems exhibit functional complexity at multiple scales, a big question has been whether effective design tools can be created to increase the sizes and complexities of the microbial systems we engineer to meet specific needs,” says Jay Keasling, director of JBEI…“Our work establishes a foundation for developing CAD platforms to engineer complex RNA-based control systems that can process cellular information and program the expression of very large numbers of genes. Perhaps even more importantly, we have provided a framework for studying RNA functions and demonstrated the potential of using biochemical and biophysical modeling to develop rigorous design-driven engineering strategies for biology…”

Synthetic biology is an emerging scientific field in which novel biological devices, such as molecules, genetic circuits or cells, are designed and constructed, or existing biological systems, such as microbes, are re-designed and engineered. A major goal is to produce valuable chemical products from simple, inexpensive and renewable starting materials in a sustainable manner. As with other engineering disciplines, CAD tools for simulating and designing global functions based upon local component behaviors are essential for constructing complex biological devices and systems. However, until this work, CAD-type models and simulation tools for biology have been very limited…

JBEI researchers are now using their RNA CAD-type models and simulations as well as the ribozyme and aptazyme devices they constructed to help them engineer metabolic pathways that will increase microbial fuel production. JBEI is one of three DOE Bioenergy Research Centers established by DOE’s Office of Science to advance the technology for the commercial production of clean, green and renewable biofuels. A key to JBEI’s success will be the engineering of microbes that can digest lignocellulosic biomass and synthesize from the sugars transportation fuels that can replace gasoline, diesel and jet fuels in today’s engines…

While the RNA models and simulations developed at JBEI to date fall short of being a full-fledged RNA CAD platform, Keasling, Carothers and their coauthors are moving towards that goal.

Cripes. Twenty-eight years ago I thought it was a big deal when I was instructing users on AutoCAD. Adding new modules to layout the drainage of subdivisions and recycle rainwater was finally possible with the horsepower we finally had in AT-level desktop computers. Woo-hoo! 🙂

Folks getting into the next generations of computational analysis are going to think they’re in a new dimension.