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Class aims to engineer blinking life in the lab

Maia Mahoney, left, a sophomore in electrical engineering and computer science, confers with graduate student Reshma Shetty of the Biological Engineering Division during the January IAP course, "Synthetic Biology Lab: Engineered Genetic Blinkers."
Maia Mahoney, left, a sophomore in electrical engineering and computer science, confers with graduate student Reshma Shetty of the Biological Engineering Division during the January IAP course, "Synthetic Biology Lab: Engineered Genetic Blinkers."

When four MIT biology and engineering faculty members designed a daring new IAP course for this year, they jokingly nicknamed it "phage wars."

The 16 students in "Synthetic Biology Lab: Engineered Genetic Blinkers" didn't end up competing to see who could make the best bacteria-attacking virus. Instead, given a small "parts kit" containing pieces of DNA, they aimed to design a biological entity that does not exist in the natural world: a one-celled system that emits a periodic signal of light, or blink.

Why make a little living lighthouse? MIT's first-of-its-kind course is expected to pave the way for a revolution in the evolving field of engineered genetic networks.

"Synthetic Biology Lab," which ran from Jan. 6-31, was created by Drew Endy, a fellow in biology and the Biological Engineering Division; Thomas F. Knight Jr., a senior research scientist in electrical engineering and computer science; Randy Rettberg, a research affiliate of the Artificial Intelligence Laboratory; and Gerald J. Sussman, the Matsushita Professor of Electrical Engineering.

Endy said that companies with the capability to synthesize long fragments of DNA have been cropping up, yet "we are almost entirely unprepared to make good use of this fabrication infrastructure because we lack the knowledge, tools and design framework necessary to systematically engineer large-scale genetic systems."

In the mid-1970s, biologists developed the ability to build genetic circuits by combining or synthesizing pieces of DNA. In the late 1990s, physicists and engineers started designing and building genetic systems using five or six components. Now, the ability to manipulate DNA makes it possible to put together dozens of components, but the work remains painstaking and difficult.

At the same time, companies such as Blue Heron Biotechnology, formed by John Mulligan (S.B. 1980), have developed methods that allow for the efficient construction of long fragments of user-specified DNA.

"One of the bottlenecks [in drug discovery] was getting access to the genes that we needed and preparing them to answer the question: Is this interesting gene a potential therapeutic target?" Mulligan said. "Gene synthesis was developed as a potential solution to this problem."

It's pricey--Blue Heron's DNA synthesis alone for the Synthetic Bio Lab course costs $80,000--but potentially faster and easier than slaving in a lab. "This class was a first attempt to decouple biological system design and debugging from the physical work of fabrication. These students didn't have to pipette or run gels," Endy said. "Design the right parts and an understandable system, put the resulting DNA into a bacteria and check to see if you have something that works."

The students (freshmen, Ph.D. candidates, electrical engineering majors and biology majors), surrounded each mid-afternoon by empty sandwich plates and soda cans, wrestled with snake-like strings of As, Cs, Gs and Ts--their engineered DNA parts projected onto a screen and scribbled on a blackboard.

The course, which took more than eight months to develop, was inspired in part by a pioneering series of classes on integrated circuit design held at Caltech and MIT in the late 1970s. Part of a search for improved, simplified methods for VLSI system design, the classes resulted in a new methodology and new products that had a big impact on the chip design industry and helped drive the personal computing and computer-communication infrastructure.

The early computer industry started with logic devices that were sold as part of logic families; the properties of the family and each individual part were documented in a data book. Like applying Henry Ford's assembly line to genomics, the MIT scientists hope to come up with something similar: a BioBricks data book.

"Synthetic biology needs such a standardization of description and a common base of parts, properties and interfaces," Rettberg said. To begin this process, the MIT scientists worked over the past year to create a data book. During the course, the students specified and designed around 50 new BioBrick parts.

By taking advantage of a standard assembly strategy developed by Knight, many combinations of parts can be assembled to create a large number of distinct systems, including different blinkers.

If "Synthetic Biology Lab" is as successful as those early VLSI system design classes, it will lead to facile control of biological information, materials and energy, Endy said.

Later this spring, when Blue Heron sends back tubes of DNA, the students will find out whether any of them managed to create a biological blinker. At minimum, the students will have created many designs of new parts that next year's class can use to create more complex designs.

"It's interesting to think about where this is actually going, and of course we have no idea," Sussman said. Knight added, "Hopefully, next IAP the students will get E. coli to blink 'dash-dash dot-dot dash' (Morse code for MIT)."

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