Our goal is to create a programming language for living cells that is similar to languages used to program computers and robots. This requires the development of a high-level language that allows a programmer to describe a desired function and computational methods that convert this language into a linear DNA sequence. The sequence is then built and inserted into an organism, which runs the program. Examples of programs built by the SBC include an edge detection program that gives bacteria to identify the light-dark interfaces in an image, a program that forms two-dimensional patters, and one that enables bacteria to count.
Genetic programming is possible because of advances in the synthesis and construction of DNA. Companies dedicated to DNA synthesis are now able to chemically build sequences to order that are hundreds of thousands of bases long with every base specified. The center is developing methods to use microfluidics to synthesize DNA and proteins in parallel. In addition, methods to assemble genetic parts are valuable in creating many variations of pathways and programs. DNA assembly can also be coupled to liquid handling robots for rapid construction and prototyping.
A vision of the center is to be able to design and program complete genomes. Recently, work out of the Venter Institute demonstrated that it is possible to reconstruct a complete bacterial genome using chemical DNA synthesis, transplant it into a host chassis, and have the new genome “boot up.” The Church lab at Harvard has developed a method called MAGE to iteratively replace the genome of a cell with a synthetic version. Whole genome design requires the convergence of multiple technologies from synthetic biology, including reliable and characterized genetic parts, synthetic regulation and genetic circuits, computer aided design, and DNA synthesis.
Natural genomes are shaped by evolution, a process of serendipity that produces complex and highly redundant genetic systems. Characterizing such a system often has the feel of peeling an onion, where there are endless layers of complex regulation. We are applying principles from synthetic biology to rebuild cellular functions from the bottom up. Natural regulation is systematically replaced with synthetic well-characterized genetic parts. This yields a “refactored” system whose genetics are fully specified. This process produces a platform for further engineering and to transfer functions between organisms. In the center, this is being applied to prokaryotic gene clusters that encode functions that include chemical synthesis, photosynthesis, and protein secretion.