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Bioengineering lab efforts tap MIT's BioBricks
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Cambridge, Mass. - Bioengineering designs were on display last week at the second annual International Genetically Engineered Machines design competition. Student teams from 13 universities in the United States, Canada and Europe met at MIT to describe their designs for building DNA-programmed molecular machines. The teams used components from MIT's Registry of Standard Biological Parts, dubbed BioBricks, for their projects.

The BioBricks library lists DNA sequences that have been artificially created by bioengineers to program specific operations inside of plant or bacterial cells (see parts.mit.edu).

While no one seemed to have produced a functioning system, the projects had varying degrees of success in getting subsystems and basic processes to work. Obstacles included the very short time span, over the summer break, in which to conduct the projects and a lack of qualified personnel to do the work. Many were working with BioBrick modular design for the first time.

In the end, the judges decided not to single out any one project as a winner. Instead, they awarded all the teams a prize simply for having tried out an idea.

Since no one actually knows how to combine modular BioBrick parts to create working molecular machines, the objectives of the design projects were primarily exploratory. The situation is reminiscent of the early days of integrated circuit design, where EEs had to contend with a lack of design tools; small, irregular wafers with wildly varying physical parameters; and no history of design successes on which to build.

In the case of bioengineered designs, the job of physical wafers in electronics is taken over by the complex interior of living cells, which act as the medium in which the DNA strands activate their coded information. It is a much more complex and variable medium than crystal silicon, however, and it often presented the teams with totally unexpected behavior.

"I am confident that once these basic issues have been resolved, we will be able to apply the engineering knowledge we have about hierarchical design, and the field will take off on an exponential curve," said Tom Knight, senior research scientist at MIT's Computer Science and Artificial Intelligence Laboratory and creator of the BioBrick library. Knight was a researcher in circuit design and computer architectures at MIT but decided to go back to school and learn molecular biology so that he could apply the hierarchical design methods of the electronics field to biology.

Knight's concept for the BioBricks registry was to leverage the success of electronic design systems in a biological context. With standard parts that are fully characterized, it should be possible to separate the various phases of biological system design into discrete levels so that, for example, someone at a workstation can hand off a design to technicians in a wet lab or biotech company facility with the confidence that it will work as specified.

Interest in the project appears to be growing rapidly in academic circles. Next year's design contest is expected to attract participants representing anywhere from 30 to 50 universities.

"We are now seeing universities setting up undergraduate courses based on the BioBrick library. It's a good way to get students involved in molecular biology at an early stage in their careers," said Randy Rettberg, who is the director of the BioBrick registry. Rettberg is actively lobbying universities to design courses based on the standardized parts.

Rettberg is an electrical engineer who spent many years at BBN Technologies and did early work on the Arpanet, which eventually became the Internet. "After 30 years of exponential growth, the electronics business seemed to be slowing. I was finding that most of my time was spent in business meetings discussing product plans," he recalled. Having known Knight in his former role as computer scientist, Rettberg became intrigued with the modular biodesign concept and decided to get involved in Knight's BioBrick project as a way of getting back into a field with an exciting growth path ahead of it.

The design contests are providing a useful first step in getting the BioBrick program off the ground by involving talented people from a wide number of fields to think in terms of biological operations.

Often, just coming up with a workable idea for a system using the specifications in the parts catalog has been a big challenge. One positive spinoff of the design competition is the addition of many new parts to the catalog, which now contains approximately 1,000 entries.

Some design concepts are taken directly from electronics. The team from ETH Zurich designed a standard state machine used in electronic systems as a counter. Instead of electrons flowing through circuits, however, the state machine uses biomolecules as signals that can be generated and suppressed with BioBrick operators. The system consists of a sensing device that detects the presence of the specific biomolecule, an event-processing component and a four-state component. The different components of the counter communicate with one another by generating signaling proteins. That capability, if implanted in cells to count biological events, would be highly useful to medical researchers and bioengineers.

A team from UC Berkeley designed a DNA sequence that could be injected into a bacteria to cause it to output fluorescent proteins with a color code to indicate temperature. The bacteria are programmed to output different proteins at different temperature ranges. As the bacteria divide and spread, the added DNA, in a circular form called a plasmid, is duplicated by the cell's machinery. The bacteria spread out through a medium and create a color-coded picture of the temperature gradient.

The team from MIT developed a black box that could be programmed to transform any biochemical signal into any other biochemical signal. The system operates by detecting a specific protein and then generates another protein, which can be programmed as an output. Such a universal signal transducer would be highly useful as a component in more-complex BioBrick designs.

Another unknown aspect of this new field is how such biological machines will ultimately be used. It seems clear that even simple systems such as the ETH counter could offer revolutionary capabilities at the research stage.

"I think the ETH Zurich team's counter is the best example of the crossover between bioengineering and electronics," said Knight.

The big picture for Knight is the possibility of creating a general-purpose nanotechnology using hierarchical design based on standardized biological parts.






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