The future of synthetic biology

Genetic engineering used to be the domain of huge research groups, but now it is gradually moving into the hands of students around the world. An annual synthetic biology competition manages to open its doors to more participants every year. Henry Stanley talks to UCL’s team and looks at the future of this emerging field.

In May 2010, Craig Venter produced the world's first 'synthetic organism', dealing vitalism a final death blow in the process. Created from a bacterium with its nucleus removed, he inserted an entirely synthetic chromosome, bearing DNA famously 'watermarked' with quotes from James Joyce and Richard Feynman. The cell promptly took on the identity written into its new genome, like a computer rebooted from a new hard disk.

Understandably, then, you might think that synthetic biology is in its youth. But while making entirely synthetic organisms is very new, genetic engineering definitely isn't: from the first E. coli cells ‘programmed’ with extra genes to produce human insulin in the late 1970s, tinkering with an organism’s DNA is a decades-old practice. What has changed is the ease and rapidity with which it can be done, with Venter’s work – producing a whole genome artificially – being the most extreme example of what is possible. iGEM, the International Genetically Engineered Machines competition, gives undergraduates a chance to try their hand at real, cutting-edge synthetic biology. Over the course of a few months, they will go from students to genetic engineers, working with other students to produce micro-organisms which have never before existed in nature.

Every summer, teams of young bioscientists assemble and, under the guidance of professors at their respective universities, try to build a synthetic organism. They are required to draw from a central repository of BioBricks, genetic building blocks which can be chained together seamlessly in a genetic circuit without reworking. Teams can also design their own BioBricks, adding them to the central repository for others to use. Teams present their work online as a wiki and as a presentation at the iGEM jamboree which takes place at MIT (Massachusetts Institute of Technology). Though there are a number of medals and prizes to be won, the Grand Prize Winner gets to take home the BioBrick trophy which, fittingly, is a large aluminium Lego brick.

A ten-strong team of UCL bioscientists spent their summer working long hours getting their genetically-engineered organism up and running. Though this is only the second time UCL has entered the competition (competing last year with a team of three), their creation is remarkable.

Typically, bacterial cultures grown in fermenters have to be ‘induced’. They first divide again and again, growing exponentially, until their growth plateaus. At this stationary point, where cell growth and cell death are occurring at equal rates, an inducer is added to the mix and the gene of interest is expressed, producing the desired protein – whether that be human insulin or vegetarian rennet. Ensuring the inducer is added at the correct time requires constant monitoring of the culture’s density. The UCL team has developed a modified bacterium that self-induces – that is, it senses when the culture’s oxygen levels spike (signalling a plateau in growth) and begins protein production all by itself.

They call it Hypoxon, and UCL’s Biochemical Engineering department thinks it could be a huge hit. Fermenters full of recombinant (genetically modified) E. coli are so common that the self-inducing bacteria could be used in thousands of different labs and plants around the world. More importantly, the system works: the team picked green fluorescent protein (GFP) for their proof-of-concept and sure enough, as the Hypoxon culture reached the right growth stage, the cells started producing the protein and fluorescing under UV light.

The team’s co-operation with the University of Bristol’s team has already guaranteed them a gold medal at the jamboree, but winning the Grand Prize will be tough. A promising vaccine against stomach ulcers was a previous winner, and this year’s entries include a bacterium for the rapid detection of waterborne parasites, a project to alter mosquitoes’ gut flora to kill the malaria parasite, and bacteria that would produce yoghurt rich in miraculin, a protein which binds to taste buds to temporarily make bitter foods taste sweet.

From the first international competition in 2005, iGEM has grown from 13 to 128 teams. The final award ceremony is now too big to take place on campus; it will instead fill a Boston convention centre. Initially a cute demonstration of the potential of assembling a few genes to make bacteria produce pulses of light, the competition has become an annual maelstrom of innovation and boundary-pushing. And as teams and universities improve their skills, better solutions emerge from their labs, and MIT’s registry of BioBricks grows. The potential of synthetic biology is just beginning to be seen, and it is young undergraduates who are pioneering some of its most interesting applications. Cut-and-paste biology is getting serious.