Synthetic biology is an emerging field that involves the design or re-design and manufacture of new biologically-inspired parts, modules, devices and systems. This has two major outputs. First, it tests scientific understanding of how life works and how it can be re-engineered at the most fundamental level. Second, it promises to put biological systems on a more modular and rational footing for subsequent engineering efforts. Foundational technologies need to be developed to make synthetic biology modular, scalable, and programmable. This project seeks to address this challenge by expanding biological space with Genetically Augmented PolymerS (GAPS) that will enable the design and manufacture of programmable networks and novel chemical function. Nucleobase amino acids (NAAs) will be synthesized and incorporated into natural polymers, proteins (pGAPS), and chemical polymers, polyvinyl nucleobases (cGAPS). In essence, by giving proteins and cells the ability to 'talk' with one another using the same code that DNA and RNA uses this proposal seeks to create a programmable ur-cell for biomedical engineering. This work will catalyze a new paradigm for engineering both chemical and biological systems. By melding the complexity and diversity of Biology with the predictability and high scalability of Chemistry, GAPS will pioneer new directions in synthetic biology. The addition of genetic information to proteins and cells will in general make biology more modular, scalable, and programmable. This should in turn enable the rational design and re-design of biological systems for compelling applications, such as controlling the wiring of interactomes and rationally modulating and programming cell function. For example, it should be possible to re-wire signaling pathways on a protein-by-protein basis, and to engineer tissues in a way that allows the precise, genetically-encoded placement of individual cells.

Broader impact: In addition to creating a wholly new ur-cell platform for synthetic biology applications, the formation of a strong a UK-US team will have a considerable impact on the global leadership by these two countries in synthetic biology. The readily grasped goals of this project (programmable cells, replicating plastic) will provide opportunities for showing the public that synthetic biology is a field that yields translational technologies that can impact their own lives. Following up on the goals of the Sandpit, the international research team will establish and maintain a valuable network that provides for competitive, interdisciplinary, and globally-engaged research. This network will directly reach out to and involve students in synthetic biology (via iGEM, the Freshman Research Initiative, and "Current Protocols in Synthetic Biology"), and will begin to train a new generation of engineers who are comfortable operating between disciplines, labs, and continents. Moreover, the network will be of great use in engaging public interest and educating policy makers about the threats and benefits of synthetic biology, overall raising awareness of the ethical, legal and social impacts of synthetic biology.

Project Report

In this collaborative grant, two research groups in the USA (Ellington, Jewett) and two groups the UK (O’Reilly, Booth) collaborated on the development and implementation of nucleic acid inspired biological and synthetic polymers containing nucleobase functionalities. Besides the new international collaborations engendered (which have survived and exceeded the length of the project), we have developed several new technologies that will continue to serve the public interest. Perhaps most importantly, Dr. O’Reilly has developed nucleobase ‘plastics’ with remarkable properties, including the ability to template their own synthesis. Such materials are likely to be of increasing importance over time, and Dr. O’Reilly continues to explore their applications with Drs. Jewett and Ellington. Dr. Jewett has continued to improve in vitro translation capabilities, now a mainstay of cell-free bioprocessing, and Dr. Ellington has greatly improved the ability to charge and utilize unnatural amino acids in such in vitro translation reactions. Dr. Ellington has developed a novel selection method to improve translation components, and in collaboration with Dr. Booth has begun to graft nucleobase functionalities onto proteins. Undergraduate and graduate student participation has been an essential part of the research, and both have been co-mentored by post-doctoral fellows. Outreach efforts by the PIs and members of their laboratories have focused on participation in the synthetic biology community, including introducing this community to new types of chemistry and to a focus on acellular biology (a field Dr. Jewett leads and was guest editor of a journal issue devoted to the subject). Educational outreach efforts included participating in the International Genetically Engineered Machine competition, and augmenting course materials with new insights into acellular biology.

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Type
Standard Grant (Standard)
Application #
0943393
Program Officer
Susanne von Bodman
Project Start
Project End
Budget Start
2009-08-01
Budget End
2014-07-31
Support Year
Fiscal Year
2009
Total Cost
$637,351
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201