iGEM 2006: The intelligent design of synthetic life

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Last weekend, 37 teams from around the world gathered at the Massachusetts Institute of Technology to take part in the International Genetically Engineered Machines Competition (iGEM).

The aim of this annual competition is to design and build biological systems that are functional in living cells. Teams consisting mainly of undergraduates and their supervisors used a catalogue of molecular components from the Registry of Biological Parts to build their machines from the bottom up. This ‘genetic toolkit’ consists of common, standardized molecular components (or ‘BioBricks’), such as promoters and other recurring biological motifs. Participants are also encouraged to build new ones to add to the toolkit.

“The key idea here is to develop a library of composable parts which we think of in the same way as Lego blocks,” says Tom Knight, an engineer at MIT who co-founded the competition with Drew Endy. “These parts can be assembled into more complex pieces, which in many cases are functional when inserted into living cells.”

In thinking up the idea of BioBricks, Endy’s main inspiration was indeed Lego. Every brick in a Lego set can be attached to any other in the set, and this is the principle behind the Registry of Biological Parts. Every component in the genetic toolkit has a ‘universal connector’ at each end, enabling it to be connected to any other component from the kit. The ‘manufacturing’ of new components, and their addition to the toolkit, will enable the building of increasingly complex machines.

“The idea is to standardize parts and the way they are put together, in the same way electrical and mechanical parts are standardized, and to be able to give people a reasonable assurance that the parts, when put together, will function as they were designed to.” But the competition also has the broader aims of “enabl[ing] the systematic engineering of biology, promot[ing] the open and transparent development of tools for engineering biology and…help[ing to] construct a society that can productively apply biological technology.”

iGEM began in 2003 as a group of MIT students who designed biological oscillators coupled to fluorescent reporter genes as part of an Independent Activity Period. The following year, 5 teams from American institutions competed in first fully-fledged Synthetic Biology competition. In 2005, 13 teams from 5 countries competed in the competition. This year, there were 37 teams from 15 countries. Each team has its own wiki page, on which details of team members and their project can be found.

This year, the grand prize was awarded to the Slovenian team, who constructed 26 new BioBricks for incorporation into a feedback loop which uses the toll-like receptor signalling pathway to decrease the response of human cells to bacterial infection. The MIT team won the award for Best System for designing bacteria which produce a mint scent during the exponential phase and a banana scent during the stationary phase. To do this, they constructed a plasmid containing enzymes that metabolize the chemical precursors into the aromatic compounds. These genes were then placed under the control of a promoter that would express them in bacterial cells, and E. coli cells were transfected with the construct. Other entries in this year’s competition included a biosensor for detecting arsenic concentrations, designed by the team from Edinburgh University, and a nanoscale device for stealth drug delivery from the Harvard team.

Life in the fast lane

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The ability of molecular biologists to transfer genes from one organism to another may seem advanced, but, in reality, these technologies are still in their infancy, and we are just beginning to get to get to grips with them. It is not so much a case of genetic engineering as genetic tinkering.

In a 1965 paper, Intel co-founder Gordon Moore proposed that the processing power of computers, as measured by the number of transistors on a silcon chip, would double every 18 months. This came to be known as Moore’s Law. Rob Carlson, a researcher at University of Washington’s Department of Electrical Engineering, has plotted graphs of the increasing efficiency of DNA sequencing and synthesis (left); these graphs look very similar to those that illustrate Moore’s law. If Carlson’s extrapolations are accurate, then by the end of the decade we will have the means to synthesize the equivalent of the human genome (3 billion base pairs) in a single day.

The teams competing in the 2006 iGEM competition had 4 months to design and build their synthetic lifeforms, some of which contain 12,000 base pairs, and represent the most complex genetic systems that have ever been ‘designed’. Even if advances in DNA sequencing and synthesis do not fulfill Carlson’s predictions, researchers, and future participants in iGEM competitions, will soon be able to produce biological components on a much larger scale than they are currently able to.

The iGEM competition and the Registry of Biological Parts are no mere flight of fancy. They may soon be at the forefront of the emerging field of synthetic biology. This new discipline poses potential problems that are far more realistic than, say, the “grey goohypothesized by opponents of nanotechnology, or the fears of those who oppose the new neurotechnologies. The potential for malicious applications of synthetic biology is amplified by the commercial availability of the molecular nuts and bolts, and the open access to protocols exemplified by MIT’s OpenWetWare wiki. The intelligent thing to do now is to ensure that synthetic forms of life are closely monitored.

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