Programming synthetic auxotrophs to depend on breakdown products of biodegradable polymers
Abstract
(Approved for public release)This Young Investigator Program award for "Programming synthetic auxotrophy to depend on breakdown prod,ucts of biodegradable polymers" is funded by the Synthetic Biology for Naval Applications Division of the Office of Naval Research a,nd amounts to $510,000 over a three-year performance period. The project seeks to help address the unmet need of the United States N,avy and Marine Corps for engineered microbial technologies that can be safely deployed on land or at sea for threat detection. The s,tudy investigates three distinct aspects related to the use of the biological containment technique known as synthetic auxotrophy to, increase its relevance for applications in the field. Synthetic auxotrophy is the engineering of an organism to create a dependence, on a synthetic nutrient for its survival. Initial demonstrations of this technique in engineered Escherichia coli cells have shown,high effectiveness at preventing escape from biocontainment under non-permissive conditions. Recent work has shown that this remains, true after long-term evolution and in co-cultures of mammalian and bacterial cells. However, additional fundamental studies are nee,ded to determine how t,s to months in the environment.The goals of this proposal are to: (1) design partial metabolic pathways that enable a model bacteriu,m to convert breakdown products of biodegradable polymers to synthetic amino acids; (2) engineer orthogonal translation machinery th,at enable cells to site-specifically incorporate different amino acids than previously reported within protein sequences; (3) invest,igate strategies to sense the concentration of synthetic amino acid for direct and more rapid regulation of engineered functions. Th, depot of required orthogonal carbon source for the engineered microbe, linking its persistence in the field to the duration of the,biodegradable polymer. These studies will shed light on important design considerations for eventual field studies of biological con,tainment by synthetic auxotrophy. Expanding the breadth of possible inputs that synthetic auxotrophs can be designed to rely on will, have significant ramifications for the practicality of biocontainment under new contexts. Additionally, the proposed design of synt,hetic amino acid sensing will help decouple the desired engineered function from organismal persistence. Knowledge gained from this,research will directly aid in the design of safeguards for responsible stewardship of engineered microbial technologies to the field,.The principal investigator, Dr. Aditya M. Kunjapur, is a tenure-track faculty member in the Chemical and Biomolecular Engineering d,epartment at the University of Delaware and has institutional and federal support for his research endeavors. He is qualified to con,duct the proposed research as evidenced by his training and publications in the areas of engineering biosynthesis of aromatic compou,nds in microbes and evolution of protein translation machinery for site-specific incorporation of non-standard amino acids. Dr. Kunj,apur s track record of research success include first-author publications in the Journal of the American Chemical Society, Proceedin,ding for societies such as AIChE and ACS, national organization such as the EBRC and BioMADE, and on-campus programs such as the Cen,ter for Plastics Innovation and the Chemistry-Biology Interface Program at the University of Delaware. His recent awards include bei,ng a 2019 ELBI Fellow, a 2020 35 Under 35 Awardee from the AIChE, the recipient of the 2021 Langer Prize, and the 2021 FFAR New Inno,vator Award.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 13, 2022
- Source ID
- N000142212536
Entities
People
- Aditya M Kunjapur
Organizations
- Office of Naval Research
- United States Navy
- University of Delaware