A synthetic gene circuit for predictive behavior in bacteria

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David Orozco-Gomez, Agustino Martnez-Antonio, Moisés Santilln-Zern

CINVESTAV-Monterrey, Mexico

Homeostasis requires bacteria to adapt to different kinds of selective pressures. They must sense and quickly respond to a great variety of signals, which usually appear to be completely random. These responses are tightly regulated under a variety of situations depending on the initial stimulus. There is a particular kind of, apparently adaptive, regulations in which a gene (or a set of genes) pre-induce other response systems; this is the basis of the so-called predictive behavior in bacteria. This phenomenon arises from the predictability of some events, in which a first signal or stimulus unchains different pathways that prepare the molecular machinery of the microorganisms to face a violent upcoming change in its surroundings. The objective of this project is to design and engineer a synthetic gene circuit that shows predictive behavior. To achieve this, we developed a deterministic mathematical model which depicts and describes the necessary parts for the circuit to work as expected; then, based on the predictions of the model, two different circuits were proposed, built and tested using E. coli as a chassis. The difference amongst both circuits is the lack of a promoter in one of the genes involved. This detail triggered several new questions regarding the differences between the mechanisms of the responses on individual cells and on a population level. In order to answer these, a stochastic model based on the data acquired from the expression of both circuits will bring new details and will help to further understand the phenomena lying beyond predictive and adaptive behavior. This circuit can be used as a new tool in synthetic biology projects, since it shares features with some other well-known pieces such as the bistable switches, but aims to more specific responses in certain operational scenarios.