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Synthetic biology: Building machines from DNA

Synthetic biology: Building machines from DNA

Cells stained for keratin and DNA: such parts ...
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Synthetic biology is a science that lies at the intersection of biology and engineering—and is therefore quite an intriguing subject for a microbiologist to venture into. The microbiologist is used to seeing cells as complex and exciting organisms to explore and DNA as the starting point at which to begin those explorations. Within the discipline of synthetic biology however the cell becomes a chassis in which to carry out engineering tasks, and the DNA the building blocks used to design intracellular machines. Although synthetic biology has been practised in different forms throughout the century, the recent increase in DNA synthesis technology development means that small genetic circuits are far easier and cheaper to make, making synthetic biology more appealing to microbiologists who want to create their own intracellular devices.

Definitions of synthetic biology vary, although there appear to be three main types. First is the “Registry” form of synthetic biology championed by (among others) Drew Endy and Tom Knight [1]. They worked on the principle that manipulatable biological parts should be standardised, to be used like nuts and bolts in machinery. This standardised approach is achieved by considering each gene, or useful piece of DNA as a brick, a “biobrick.” Each biobrick can be stored on a plasmid, a circular loop of DNA that can be easily inserted into cells.

By using these standard parts whole intracellular systems can be built up, for example to turn on a fluorescent protein in the presence of a dangerous pollutant such as lead, or arsenic. Viewing the DNA as simply boxes that can be joined and separated creates a higher level of abstraction to allow engineers and other non-biologists to create machines without needing to know biological details of the workings of DNA. This in turn allows more complex systems to be designed, such as biological amplifiers, oscillators, random number generators[2], and even biological camera film[3]. All the parts are stored in a biobrick registry (a giant freezer!) at the Massachusetts Institute of Technology and the details of each part can be found online (http://parts.mit.edu).

The second form of synthetic biology is more concerned with affecting the output of important biological molecules than with building intracellular machines. Many drugs, such as antibiotics, are formed from bacterial products and there is therefore a lot of interest in both increasing the production of these drugs and in tweaking the cells to produce slightly different variations of the antibiotics, to help combat bacterial antibiotic resistance.

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As well as using partially-synthetic systems to improve drug production, these synthetic biology systems also allow further biological exploration of how antibiotic pathways work. Recent research produced a cell which contained only all the necessary genes for life, with none of the genes usually used for antibiotic production [4]; addition of separate antibiotic-production pathways into this cell could help to explore how these pathways interact and potentially how to encourage cells to activate pathways for new antibiotics. This is considered by some to be not ‘true’ synthetic biology as it doesn’t involve standard parts or large constructions, but as it consists of creating novel forms of life by purposefully manipulating the DNA towards a desired end, I think it counts as synthetic biology.

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