Evolution machine: Genetic engineering on fast forward | Journal ...

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Automated genetic tinkering is just the start ? this machine could be used to rewrite the language of life and create new species of humans

IT IS a strange combination of clumsiness and beauty. Sitting on a cheap-looking worktop is a motley ensemble of flasks, trays and tubes squeezed onto a home-made frame. Arrays of empty pipette tips wait expectantly. Bunches of black and grey wires adorn its corners. On the top, robotic arms slide purposefully back and forth along metal tracks, dropping liquids from one compartment to another in an intricately choreographed dance. Inside, bacteria are shunted through slim plastic tubes, and alternately coddled, chilled and electrocuted. The whole assembly is about a metre and a half across, and controlled by an ordinary computer.

Say hello to the evolution machine. It can achieve in days what takes genetic engineers years. So far it is just a prototype, but if its proponents are to be believed, future versions could revolutionise biology, allowing us to evolve new organisms or rewrite whole genomes with ease. It might even transform humanity itself.

These days everything from your food and clothes to the medicines you take may well come from genetically modified plants or bacteria. The first generation of engineered organisms has been a huge hit with farmers and manufacturers ? if not consumers. And this is just the start. So far organisms have only been changed in relatively crude and simple ways, often involving just one or two genes. To achieve their grander ambitions, such as creating algae capable of churning out fuel for cars, genetic engineers are now trying to make far more sweeping changes.

Grand ambitions

Yet changing even a handful of genes takes huge amounts of time and money. For instance, a yeast engineered to churn out the antimalarial drug artemisinin has been hailed as one of the great success stories of synthetic biology. However, it took 150 person-years and cost $25 million to add or tweak around a dozen genes ? and commercial production has yet to begin.

The task is so difficult and time-consuming because biological systems are so complex. Even simple traits usually involve networks of many different genes, which can behave in unpredictable ways. Changes often do not have the desired effect, and tweaking one gene after another to get things working can be a very slow and painstaking process.

Many biologists think the answer is to try to eliminate the guesswork. They are creating libraries of ready-made ?plug-and-play? components that should behave in a reliable way when put together to create biologicial circuits. But George Church, a geneticist at Harvard Medical School in Boston, thinks there is a far quicker way: let evolution do all the hard work for us. Instead of trying to design every aspect of the genetic circuitry involved in a particular trait down to the last DNA letter, his idea is to come up with a relatively rough design, create lots of variants on this design and select the ones that work best.

The basic idea is hardly original; various forms of directed evolution are already used to design things as diverse as proteins and boats. Church?s group, however, has developed a machine for ?evolving? entire organisms ? and it works at an unprecedented scale and speed. The system has the potential to add, change or switch off thousands of genes at a time ? Church calls this ?multiplexing? ? and it can generate billions of new strains in days.

Of course, there are already plenty of ways to generate mutations in cells, from zapping them with radiation to exposing them to dangerous chemicals. What?s different about Church?s machine is that it can target the genes that affect a particular characteristic and alter them in specific ways. That greatly increases the odds of success. Effectively, rather than spending years introducing one set of specific changes, bioengineers can try out thousands of combinations at once. Peter Carr, a bioengineer at MIT Media Lab who is part of the group developing the technology, describes it as ?highly directed evolution?.

The first ?evolution machine? was built by Harris Wang, a graduate student in Church?s lab. To prove it worked, he started with a strain of the E. coli bacterium that produced small quantities of lycopene, the pigment that makes tomatoes red. The strain was also modified to produce some viral enzymes. Next, he synthesised 50,000 DNA strands with sequences that almost matched parts of the 24 genes involved in lycopene production, but with a range of variations that he hoped would affect the amount of lycopene produced. The DNA and the bacteria were then put into the evolution machine.

The machine let the E. coli multiply, mixed them with the DNA strands, and applied an electric shock to open up the bacterial cells and let the DNA get inside. There, some of the added DNA was swapped with the matching target sequences in the cells? genomes. This process, called homologous recombination, is usually very rare, which is where the viral enzymes come in. They trick cells into treating the added DNA as its own, greatly increasing the chance of homologous recombination.

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Source: http://journaltec.com/2011/06/27/evolution-machine-genetic-engineering-on-fast-forward.html

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