Abstract

The ability to engineer programmable biological systems using complex artificial gene networks has great potential to unlock important innovative solutions to many biotechnological challenges. While cells have been engineered to implement complex information processing algorithms and to produce food, materials, and pharmaceuticals, many innovative applications are yet to be realized due to our poor understanding of how robust, reliable, and predictable artificial gene circuits are built. In this work, we demonstrate that robust complex cellular behaviors (e.g., bistability and gene expression dynamics) can be achieved by engineering gene regulatory architecture and increasing the complexity of genetic networks. We further demonstrate that increasing demand for cellular resources causes resource-associated interference among noninteracting genetic devices of various complexities. Importantly, we show that feedback systems can be engineered to enhance the robustness and reliability of genetic circuits by reducing such resource-associated interference among independent circuits. Taken together, this work contributes to understanding the design principles that govern biological robustness and represents an important step towards construction of robust, tunable, reliable, and predictable complex artificial genetic circuits for a wide range of biotechnological applications.

Committee Chair

Tae Seok Moon

Committee Members

Michael Brent, Himadri Pakrasi, Yinjie Tang, Fuzhong Zhang,

Comments

Permanent URL: https://doi.org/10.7936/zasx-vf36

Degree

Doctor of Philosophy (PhD)

Author's Department

Energy, Environmental & Chemical Engineering

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

Summer 8-15-2018

Language

English (en)

Author's ORCID

https://orcid.org/0000-0003-2100-1400

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