Genetic circuit characterization by inferring RNA polymerase movement and ribosome usage.

ABSTRACT: To perform their computational function, genetic circuits change states through a symphony of genetic parts that turn regulator expression on and off. Debugging is frustrated by an inability to characterize parts in the context of the circuit and identify the origins of failures. Here, we take snapshots of a large genetic circuit in different states: RNA-seq is used to visualize circuit function as a changing pattern of RNA polymerase (RNAP) flux along the DNA. Together with ribosome profiling, all 54 genetic parts (promoters, ribozymes, RBSs, terminators) are parameterized and used to inform a mathematical model that can predict circuit performance, dynamics, and robustness. The circuit behaves as designed; however, it is riddled with genetic errors, including cryptic sense/antisense prom

SUBMITTER: Espah Borujeni A 

PROVIDER: S-EPMC7536230 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature