Programming genetic circuits for new biological functions
Scientists at the Massachusetts Institute of Technology (Cambridge, US) have developed a programming language to design DNA-circuits. The circuits can implement specific and new functions for cells, leading towards efficient and highly repetitive modular genetics.
The idea behind the research is relatively straightforward. Cells interact with the environment, make decisions and perform tasks a bit like ‘computational operations’ – a dedicated network of regulatory proteins acquire external signals and specific genes are expressed, timely, in response to the stimuli. Based on this premise, a group of researchers at MIT developed a programming language that anyone can use to write a specific function, e.g. a certain response to an environmental trigger, which can then be translated into a DNA sequence to realize it.
“It is literally a programming language for bacteria,” says MIT professor of biological engineering, Christopher Voigt. “You use a text-based language, just like you’re programming a computer. Then you take that text and you compile it and it turns it into a DNA sequence that you put into the cell, and the circuit runs inside the cell.” The technique is described in the current issue of the journal Science.
The technology is somewhat of a paradigm shift. Up to now, biologists and engineers have designed genetic parts such sensors, switches and biological clocks that, once combined, could be used to alter existing cell functions or add new ones. This however, is a laborious process with a lot of trial and error. The new programming language overcomes this. “You could be completely naive as to how any of it works. That’s what’s really different about this,” Voigt says. “You could be a student in high school and go onto the Web-based server and type out the program you want, and it spits back the DNA sequence.”
Currently, the language is optimized for Escherichia coli, but the researchers are working on expanding it to other strains of bacteria, including some bacteria commonly found in the human microbiome and plants. Using the language, the researchers programmed 60 circuits for E. coli that were transformed into DNA sequences and were then built. The assembly of the sequences required 880,000 base pairs of DNA in total. Out of 60, 45 circuits performed correctly in every output of the state, and overall 92% of the total 412 output states functioned as predicted.
The next step for the researchers at MIT is to design bacteria with specific functions, e.g. bacteria to aid digestion of lactose, bacteria living on plants that work as insecticides and yeast that shuts itself off when there are too many toxic bio-products in a fermentation reactor.
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