Design and Evolution of Engineered Biological Systems

Abstract

To date, engineered biological systems have been constructed via a variety of ad hoc approaches. The resulting systems should be thought of as pieces of art. Here, I propose to explore how existing forward engineering approaches might be combined with evolution to make routine the construction of engineered biological systems. I will specify a procedure for construction of biological systems via screening of subcomponent libraries and rational re-assembly. I will develop tools to enable this approach including a high-throughput screening system to measure the input/output function of an arbitrary genetic device. I will apply this approach to construct a collection of ring oscillators and bi-stable switches. Furthermore, I anticipate that performance of these devices will decay over time due to spontaneous errors in replication of the genetic information encoding the systems. As an engineer, I would like to be able to design systems with behavior that is predictable in the face of mutation and selection. I will explore mechanisms for increasing or decreasing the susceptibility of engineered biological systems to loss of function as a result of mutation.