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Engineering meets Biology
Tuesday, 10 June 2008

Biology is full of fascinating marvels, performing complex processes at the nanoscale and with low energy demand. A new generation of engineers is now adding design and intention to biology by crafting newly built genetic parts into microorganisms and living cells. They promise a vast range of applications, from biomedicine to energy production, and the emergent field-synthetic biology-has the potential to bring about a major revolution in the technological landscape of the future.

The most popular aspiration of synthetic biology is the production of microbes with custom-made genomes that synthesize natural products of commercial interest. Engineered yeast cells that produce a highly effective anti-malarial compound known as artemisin, which is only found in small quantities in plants, are their current trophy. The challenge now is to broaden the range of products, the set of genetic instructions inserted into host microorganisms to code new biosynthetic pathways and fine-tune the efficiency of the processes. The principle could then be applied to the cheap production of biopharmaceutical compounds and more general industrial chemicals, or even pave the way to the development of new biomaterials with useful properties. One of the most exciting possibilities is the potentially positive impact on the environment by enabling sustainable energy production-engineered bacteria may well be turned into powerhouses of the future, producing biofuels or even filling the ranks of a green army designed to degrade toxic waste.

The radical approach of this new discipline is to build from scratch organisms from a biological Lego set. And what better way to start than rewriting the code of life? By adding artificial nucleotide bases to the existing four letter alphabet (A, T, C, G) scientists are creating an artificial genetic code with potentially interesting applications. To date this innovative idea has been exploited in healthcare and in the development of more sensitive diagnostics of infectious agents. But the possibilities are expanding as new types of DNA-called TNA and xDNA-are more stable and thus are attractive raw materials for laying out the genetic information to be delivered into microorganisms and living cells.

But scientists are not content with adding new characters to the alphabet but are also trying to translate forbidden words of the natural genetic code into new amino acids, the building blocks of proteins (see diagram). The aim is to increase the repertoire of proteins, for example enzymes, inside the cell and explore new useful properties that could for instance make them more effective as drugs.

And if you think that is pushing biology too far, be prepared for more tricks. The holy grail of the field is to endow engineered devices with life, to create machines in symbiosis with living cells. The idea is to make cells programmable through a device integrated within the cell at a molecular level. As complex as it may seem, the first steps taken towards this goal have been fairly simple and are inspired from electronic components. Scientists are creating DNA components-nicknamed BioBricks-that perform logic functions, such as turning a gene on or off, and that could be combined into more complex genetic circuits to produce a final output. The potential outcomes of applying this approach borrow from science fiction. One can imagine devices built into human cells that perform 'surveillance' functions: a mechanism counting the number of times a cell divides and instructing it to self-destruct at a set number to prevent tumours. Another would sense damaged tissue and repair it. A new generation of drugs consisting of a synthetic molecular assembly could sense molecules associated with certain diseases and make diagnoses by activating the drug. Perhaps more ambitious still is the promise of achieving a more efficient programming of human stem cells to manufacture insulin-producing 'beta cells' to be transplanted into the liver of diabetic patients. But, the manipulation of biological systems is complicated and this challenge will keep scientists busy in decades to come.

Apart from satisfying the curiosity of tinkering with life, the new technologies based on DNA are also appealing because they are cheap. Moreover, industries based on them can be easily implemented locally, in the developing world, regulatory and patenting framework permitting.

Alexandra Lopes

 
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