Computing with living hardware

Our multi-institutional team of eleven undergraduates, one high school student, one postdoctoral fellow, and four faculty members explored the emerging field of synthetic biology and presented our results at the 2006 international Genetically Engineered Machine (iGEM) competition. Having had little or no previous research experience, biology, chemistry and mathematics students from four different institutions collaborated during the summer and fall semester of 2006. We identified the burnt pancake problem (sorting by reversals) as a mathematical puzzle ideal for solving with ‘living computer hardware’: Escherichia coli cells programmed to sort tandem fragments of DNA by reversals (DNA inversions or ‘flipping’). Flipping is driven by a Salmonella typhimurium Hin/hix recombinase system that we reconstituted as a collection of BioBrick-compatible interchangeable parts. We tested functionality of these synthesised genetic parts and mathematically modeled the behaviour of pancake flipping. The living hardware system allowed us to consider future research applications such as regulating genetic element rearrangements in vivo and DNA computing. We found the field of synthetic biology to be ideal for learning, teaching, sharing, collaborating, and conducting integrative and original research with undergraduates. 1 Aims of the project: a biological approach to solving a mathematical puzzle Our team set out to engineer bacteria in order to build living computer hardware that can compute solutions to a mathematical puzzle called the burnt pancake problem. The puzzle can be thought of as a stack of different sized pancakes, each having one burnt side and one golden side, arranged in an arbitrary order. The goal is to rearrange the pancakes by flipping individual pancakes or subsets of adjacent pancakes until the pancakes are sorted from largest to smallest with each pancake facing golden side up. In computer science this process is called sorting by reversals. As the pancake stack becomes larger, the number of possible arrangements increases and the problem becomes computationally intractable. To produce essentially unlimited computing power, we decided to harness the power of Escherichia coli DNA replication and cell division. We # The Institution of Engineering and Technology 2007 doi:10.1049/iet-stb:20070004 Paper first received 18th January 2007 K.A. Haynes, S. Rosemond, S. Simpson, E. Zwack and A. Malcolm Campbell are with the Biology Department, Davidson College, Davidson, NC 28036,