Oscillator

Designing emergent behavior

Groups of individuals (from molecules to cells to animals) following simple rules and responding to environmental cues will create the amazingly complex emergent behaviors we see in nature, making cells, bodies, and societies far more than the sum of their parts. Each individual acts without knowing what the final outcome will be, whether it’s birds flying in formation, termites building intricate underground tunnels, or human societies building cities and networks. At a molecular level, one of the most striking examples of emergent behavior is embryonic body pattern formation. Every cell in the embryo has an identical copy of the genome, but each cell activates a specific set of genes depending on the concentration of chemicals in its environment, concentrations defined by the orientation of the egg and neighboring cells. By following simple rules for the transcription of different genes at different times in different places, the embryo goes from an undifferentiated mass of cells to a real creature.

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Of course, it’s not really that simple. In order to make an embryo each cell has to follow hundreds of simple rules, making a very complicated whole. The picture above is from a database of gene expression patterns in the embryo of the fruit fly, Drosophila melanogaster, called Fly-FISH, where researchers systematically look at expression of many different genes in the embryo, comparing the different patterns of expression and collecting tons of data. This data feeds into our understanding of how genetic programs lead to development, how bands of differential gene expression in identical cells can turn into very different body parts–head, thorax, wings, abdomen, legs.

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Even in the simplest single-celled organisms, bacteria, gene expression changes in response to the outside environment and the behavior of each cell’s neighbors can lead to incredible pattern formation, moving as “microbial societies”. Myxobacteria join together when times are tough and food is scarce to form a “fruiting body”. Every cell has the same chromosome, but by communicating and working together, different cells activate different cellular pathways to become different parts of the fruiting body, including a huge number of cells that commit suicide to provide food to the remaining population!

Synthetic biology too aims to create complex emergent behavior through the implementation of simple biological rules in populations of individual cells. Starting from just three genetic control elements and a fluorescent protein, synthetic biologists have made bacterial populations that can integrate environmental signals and behave as toggle switches, boolean logic gates, and even oscillators. By adding genes that allow bacteria to signal to one another as they do in nature, one can see patterns emerge on the petri dish. A great paper from 2005 shows how by connecting expression of fluorescent proteins to the local concentrations of bacterial “pheromones” that diffuse across the dish, patterns can emerge depending on how cells are seeded onto a plate.

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Since then, iGEM teams have used similar techniques to make all kinds of patterns, including the Osaka team in 2009 with their hypnotizing swirls and fluorescent Mario:

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The Cambridge iGEM team in 2008 and other labs are working towards more complex pattern formation, known as the Turing pattern:

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These are admittedly “toy” systems, but as synthetic biological circuits become more complex, the control of populations of cells in a precise way will undoubtedly be critical. Adding more rules and circuits that control different genes will lead to more complex and useful patters and a deeper understanding of the emergent properties of gene networks.