Team:HZAU-China/Project

Background

Since its inception more than a decade ago, synthetic biology has undergone considerable development and has attained significant achievements with the help of the engineering slant. However, there are still obstacles to build a cell. Engineers try to abstract the DNA sequences into some standard functional parts and assemble them using some principles in electrical engineering. So far, the limited understanding of biological system prevents them to combine parts and modules to create larger scale systems. The complexity of synthetic systems didn’t increase rapidly as the Moore’s law (Purnick and Weiss, 2009).

Challenges

There are some common problems that make the circuits we designed not work as our expected. Many failure modes have been collated by Brophy and Voigy in their review (Brophy and Voigt, 2014). In our project, we mainly focus on two modes, crosstalk and host overload, that emerge especially when we create more sophisticated systems. More specifically, regulators may interact with each other’s targets leading to errors in the desired operation, and the synthetic circuits may compete with natural parts that maintain the normal cellular processes for limited resources.

Solution

We design a time-sharing system that can process information according to the input signal. Cells rewire its synthetic circuit to alter the topological structure of regulatory pathway when they receive the corresponding stimuli. In this way, we reuse the existing synthetic module rather than add a new one to implement another function, which reduces the resource cost in running unnecessary function and the interplay between parallel modules. After overcoming these two big problems, our engineered cells are more versatile and flexible in information processing.

Design Overview

Our system of the rewirable circuit is composed of three modules, including an input module, a processing module, and an output module. The input module acts as a sensor and a trigger. It receive the environment signal and expresses recombinase to rewire the processing module. The processing module is a small gene regulatory network with some specific sites for DNA recombination that lead to rearranging the connection of parts. In order to confirm the functions, we need an output module to monitor the real-time processes. Here we use fluorescence intensity as an indicator. This is the first step. Once its function is confirmed, we can use other functional proteins as output to solve real world problems.