Synthetic 'upgrade' for fruit fly's DNA

The genetic code of the fruit fly Drosophila has been hacked into, allowing it to make proteins with properties that don't exist in the natural world. The advance could ultimately lead to the creation of new or "improved" life forms in the burgeoning field of synthetic biology.

The four letters of the genetic code, A, C, T and G, are read in triplets, called codons, by the cell's protein-making machinery. Each codon gives an instruction for the type of amino acid that gets added next in a protein chain, or tells the machinery to stop.

Jason Chin at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, and colleagues previously showed that it was possible to reassign one of these stop codons to incorporate an "unnatural" amino acid instead, and last year they engineered nematode worms to manufacture such proteins.

Complex proposition

However, fruit flies are a much more complex proposition. "They contain significantly more neurons; they can learn; they have all sorts of complicated behaviours," says Chin. "Many of the things we've discovered in biology have actually been discovered in flies."

Now, as a proof of principle, Chin's team has engineered fruit flies that incorporated three new amino acids into proteins in the cells of their ovaries.

The flies were engineered using bacteria that had been modified to insert the genetic code for the unnatural amino acid into the fly DNA. There was no apparent impact on the flies' health, and they even produced healthy offspring that also made the new protein chains.

"This work provides a very significant expansion on our capability to manipulate and alter proteins involved in specific cellular and developmental processes. It will provide new insights into human disease mechanisms, memory and ageing," says Paul Freemont of the Centre for Synthetic Biology and Innovation at Imperial College London.

Bulletproof flies

None of the amino acids were particularly remarkable, but the fact that engineering the flies had no obvious impact on their health suggests that many more useful amino acids could be similarly incorporated.

For example, work in bacterial cells has shown that it is possible to incorporate unnatural amino acids that cross-link to each other or turn an enzyme's activity on or off when a light is shone on them. Doing this in a complex organism like a fly could shed new light on how proteins interact within cells, or how rapidly turning an enzyme on or off affects the cell's function.

The technique could even be used to create animals with new or improved properties, although that is probably some years off. "We're not going to be creating bulletproof flies or anything like that in the short term," says Chin.

Journal reference: Nature Chemical Biology, DOI: 10.1039/nchembio.1043

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