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.

References

Purnick, P. E., & Weiss, R. (2009). The second wave of synthetic biology: from modules to systems. Nature reviews Molecular cell biology, 10(6), 410-422.

Brophy, J. A., & Voigt, C. A. (2014). Principles of genetic circuit design. Nature methods, 11(5), 508-520.

Siuti, P., Yazbek, J., & Lu, T. K. (2013). Synthetic circuits integrating logic and memory in living cells. Nature biotechnology, 31(5), 448-452.

Callura, J. M., Cantor, C. R., & Collins, J. J. (2012). Genetic switchboard for synthetic biology applications. Proceedings of the National Academy of Sciences, 109(15), 5850-5855.

Paige, J. S., Wu, K. Y., & Jaffrey, S. R. (2011). RNA mimics of green fluorescent protein. Science, 333(6042), 642-646.

Mohammad, H. P., & Baylin, S. B. (2010). Linking cell signaling and the epigenetic machinery. Nature biotechnology, 28(10), 1033-1038.

Zhang, X. P., Liu, F., & Wang, W. (2011). Two-phase dynamics of p53 in the DNA damage response. Proceedings of the National Academy of Sciences,108(22), 8990-8995.