INSPIRE Track 1: Protocells as a Platform for Bottom-up Synthetic Biology

University Of California-San Diego, La Jolla CA

Investigators

Abstract

1344298 Wang This INSPIRE award is partially funded by the Biotechnology,Biochemical and Biomass Engineering Program in the CBET Division in the Directorate for Engineering, the Synthetic and Systems Biology Program in the Division of MCB in the Directorate for Biological Sciences, the Biomaterials Program in the Division of DMR in the Directorate for Mathematics and Physical Sciences, and by the Office of International and Integrative Activities. In this project artificial cells will be engineered with defined building blocks that may be as small as individual genes, proteins, and RNA. The platform that enables this approach is the protocell, a nanoengineered construct built by directed self-assembly that provides for independent definition of the cell interior and the surface membrane. In this bottom-up approach it is exactly known what is in the cell, and, therefore, uncontrolled variables are minimized. Initially a proof-of-concept will be developed in which a signaling pathway including both membrane and intracellular components is assembled, leading to greater complexity as more components are added. Ultimately a minimal living cell with basic functions will be engineered and studied. Accordingly, three major goals of the proposal are: (1) to create a general synthetic biology platform to study signal transduction and protein synthesis with controlled parameters; (2) to build mechanistic models governing the signal transduction and protein synthesis inside the synthesized cell; (3) to bridge the gap between in vitro and in cell experiments. These goals will be achieved by employing successive versions of protocells designed and fabricated with increasing levels of complexity. By integrating nanoscience, molecular biosensors, imaging, and biochemistry in the context of systems biology and synthetic biology, a highly interdisciplinary platform to reconstitute and model cellular complexity will be established providing a general and systematic approach to understand the design principles of molecular networks in a cellular environment. This work will have fundamental implications for understanding information flow in biomolecular networks and directed self-assembly at the nanoscale. As such, the success of this project will have transformative impact on bionanotechnology and biomimetic devices. In addition, the research will be integrated with educational efforts to ensure that undergraduate and high school students and particularly underrepresented groups have the opportunity and encouragement to work in cutting-edge interdisciplinary research.