CAREER: Preventing Evolutionary Failure in Synthetic Biology

University Of Texas At Austin, Austin TX

Investigators

Abstract

1554179 Barrick, Jeffrey E. Synthetic biology applies engineering principles to create living systems with predictable and useful behaviors from collections of standardized genetic parts. However, living systems - unlike mechanical devices - inevitably evolve when their DNA sequences accumulate copying errors, often resulting in "broken" cells that no longer function as they were programmed. This project will address this problem by better characterizing how engineered cells evolve and using this information to design DNA sequences and host cells that are reinforced against unwanted evolution. Decreasing the incidence of evolutionary failures in bioengineering will have broad benefits: increasing the complexity of DNA-based devices that can be constructed and used for the sustainable production of biofuels and drugs; limiting the potential dangers of unpredictable evolution when genetically modified organisms are used in future applications outside of the laboratory; and inspiring a new generation of students to pursue careers in science and technology by improving the chances that their first synthetic biology projects are successful. For efforts ranging in scale from constructing small genetic circuits and metabolic pathways to international research consortia rebuilding entire microbial genomes, stopping - or at least slowing - evolution would greatly improve the efficiency of biological engineering. This research will: (i) create software to predict evolutionary weaknesses (failure modes) in the DNA sequences encoding devices so that they can be avoided at the design stage, (ii) develop high-throughput experimental techniques based on next-generation DNA sequencing to more fully characterize these failure modes and improve these predictions, and (iii) use directed evolution and genome editing to create variants of organisms that are common chassis for synthetic biology with reduced mutation rates. These research activities are integrated with education by supporting an undergraduate International Genetically Engineered Machine (iGEM) team at the University of Texas at Austin and their graduate student mentors. They will standardize methods for measuring the evolutionary reliability of biological devices and improve the stability of popular genetic parts in the Registry of Standard Biological Parts, a resource used worldwide in education and research. Hispanic students and women will specifically be involved in the iGEM team so that this project directly contributes to the development of a diverse STEM workforce. This CAREER award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biosciences.