EVO-ENGINE: A directed evolution engine for engineering proteins and logic gates

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Natural selection is the most powerful force in biology and drives the evolution of complex organisms, such as ourselves, simply by continually enriching for those that survive and replicate. This has been long exploited in the field of "directed evolution" which copies natural selection in an artificial manner, to obtain useful proteins. Directed evolution allows us to make proteins with complex properties that would be impossible to achieve by design alone. Perhaps the best-known example is the now widely-used cancer drug, Herceptin, which was originally evolved in the laboratory using a technique called "phage display". This method uses tiny viruses called phage - which only infect bacteria - to evolve new proteins. Randomised proteins are made by the phage and only ones which stick to a desired target are retained and survive - and so they are said to be evolving. At the end of each experiment, the proteins are recovered and can be made in large quantities and purified. Around 20 drugs made by artificial selection (phage display) are already approved for use in humans or are in in late stage clinical trials. This technology is therefore very powerful and has already benefited humanity greatly. It is possible to use phage and directed evolution not just for making proteins with new "sticky" properties but for engineering complex functions. Moreover, there is a new scientific field called synthetic biology which aims to re-engineer biological networks and systems to make useful enzymes, molecules and even small machines - such as biological computers and selective cancer cell modulators. One branch of synthetic biology aims to generate genetic circuits - similar to the logic gates that are used in standard electronics and computers - and these are currently made very laboriously, one-by-one, with a huge amount of trial-and-error. By applying directed evolution we believe that we can save a lot of time and effort by simply evolving logic gates in phage and bacteria, in order to obtain a new generation of useful biological tools. We have already built a prototype robot (The EVO-ENGINE) that grows phage and bacteria under a series of selective pressures. In this way, only the ones containing a functional logic gate survive. Over time, with random mutations, and increasing selection pressures, better and better logic gates evolve. The resulting components have a vast range of biotechnology applications, such as making biological sensors (for example, to detect pollutants in the environment) or for controlling synthesis circuits in bacteria to make useful products (plastics, fuels and medicines). We are only beginning to harness the power of directed evolution - which nature has exploited for millions of years - and this BBSRC-funded project has the potential to provide a major advance.