SAN DIEGO, Calif. Synthetic biology reared its 21st century head here at the Design Automation Conference, and it looks like a lot of it could be generated by tomorrow's EDA tools.
At a special session on synthetic biology on Thursday (June 7), Ron Weiss, researcher at the department of electrical engineering and molecular biology at Princeton University, said "we have developed an integrated computational/experimental approach to engineering complex behavior in living systems ranging from bacteria stem cells."
Weiss detailed how in his team's research appropriated useful design principles from electrical engineering and other well established fields including abstraction, standardization, modularity, and computer aided design. "We can now regard cells as 'programmable matter'," said Weiss. "Through genetic engineering, we are equipping cells with new sophisticated capabilities for gene regulation, information processing, and communication."
These new capabilities serve as catalysts for synthetic biology, an emerging engineering discipline to program cell behaviors as easily as programming computers, said Weiss.
In their research, Weiss and his colleagues use computer engineering principles of abstraction, composition, and interface specifications to build programmable organisms with sensors and actuators precisely controlled by analog and digital logic circuitry. Recombinant DNA-binding proteins represent signals, and recombinant genes perform the computation by regulating protein expression.
"We have built synthetic gene networks that implement biochemical logic circuits in a variety of cell types including Escherichia coli, Saccharomyces cerevisiae (yeast), and mammalian stem cells," Weiss said. He noted that these circuits incorporate a variety of digital and analog devices, including the AND, NOT, and IMPLIES logic gates and analog signal amplifiers.
Recently, Weiss and his team have obtained preliminary experimental results towards demonstrating precise spatiotemporal control over stem cell differentiation. They have initiated work for creating an artificial tissue homeostasis system where genetically engineered stem cells maintain indefinitely a desired level of pancreatic beta cells despite attacks by the autoimmune response. The system, which relies on artificial cell-to-cell communication, various regulatory network motifs, and programmed differentiation into beta cells, may one day be useful for the treatment (or cure) of diabetes, according to Weiss.
Lingchong You, a researcher at the Institute for Genome Sciences & Policy at Duke University, discussed their efforts to reprogram bacteria as therapeutic agents, for example, to deliver drugs or to selectively kill tumor cells. To realize this goal, bacterial dynamics must be precisely controlled, including growth, death, and aggregation, under diverse conditions. Combining modeling and experimentation, You's lab has been exploring design strategies to achieve such control by engineering a series of synthetic killer circuits in the bacterium Escherichia coli.
"The use of synthetic killer circuits is the key for quantitatively defining the tradeoff characteristics in controlling bacterial population dynamics. Their implementation, testing, and refinement in well-defined conditions will provide
fundamental insights into the precise containment of engineered bacteria for therapeutic or environmental applications," said You.
Jeffrey Tabor, researcher at the University of California in San Francisco, has reprogrammed the genomes of living cells to construct massively parallel biological computers capable of processing two-dimensional images at a theoretical resolution of greater than 100 megapixels per square inch.
"The programming of community behavior is an important challenge for synthetic biology, as it may facilitate the study of natural developmental mechanisms and have applications in technologies such as tissue engineering," said Tabor.
He is convinced that the work stands as a demonstration of our ability to use the massive parallelism inherent to biology to directly solve computational problems which are exceedingly challenging for traditional silicon-based systems.
In this way, Tabor paid tribute to the recently departed Richard Newton, a visionary EE who saw synthetic biology as the next frontier for chip designers and EDA tool developers. Newton's seminal work of melding electrical engineering with biology was honored in a DAC keynote speech by his friend Jan Rabaey, professor of electrical engineering and computer science at the University of California at Berkeley.