Endy:Chassis engineering

Abstract

The engineering of biological systems with predictable behavior is currently a challenging problem. A major reason for this difficulty is the complexity and variation found in cells acting as a host to engineered biological systems and the numerous interactions between the host and system. To make the future engineering of biological systems easier, I will study and optimize the interface between an engineered biological system and its host cell or '"chassis". An optimal design of the host/system interface should essentially decouple system function from host function, such that newly designed systems work as predicted first time with less need for iterative design. Ultimately this will lead to the development of a host engineering field to complement the system engineering field. With a standardized and specified host/system interface any system will function in any host designed for the same interface. This interchangeability of modules has been a powerful enabler in other engineering disciplines. I will accomplish these overall goals by first specifying and testing the interaction between a host and an engineered system to better characterize the effects of one on the other. I will then build dedicated transcription and translation systems, independent from the equivalent host systems. The goal of these systems is to decouple system function from host function wherever possible. Lastly, I will use the isolated systems as a tool to further examine the interactions between a system and its host.

Specific Aims

• Integrate dedicated transcription and translation systems into a chassis
• Develop test systems & measurements to evaluate chassis response to system demands
  • Applying and measuring translation demand
• Evaluate the ability of a wild-type chassis and a dedicated system containing chassis to supply an engineered system
  • Demand modeling
• Investigate “porting” an engineered system between two chassis