Mediating Ribosomal Competition by Splitting Pools

TL;DR

This paper extends the Ribosomal Flow Model to include orthogonal ribosomes, demonstrating stability and optimizing resource allocation to improve synthetic gene expression in cells.

Contribution

It introduces the Orthogonal Ribosomal Flow Model (ORFM), incorporating orthogonal ribosome competition, and provides stability analysis and an optimization framework.

Findings

ORFM is proven to be stable using Robust Lyapunov Functions.

Optimization of ribosomal resource allocation enhances protein translation rates.

The model offers a new approach to mitigate ribosomal competition in synthetic biology.

Abstract

Synthetic biology constructs often rely upon the introduction of "circuit" genes into host cells, in order to express novel proteins and thus endow the host with a desired behavior. The expression of these new genes "consumes" existing resources in the cell, such as ATP, RNA polymerase, amino acids, and ribosomes. Ribosomal competition among strands of mRNA may be described by a system of nonlinear ODEs called the Ribosomal Flow Model (RFM). The competition for resources between host and circuit genes can be ameliorated by splitting the ribosome pool by use of orthogonal ribosomes, where the circuit genes are exclusively translated by mutated ribosomes. In this work, the RFM system is extended to include orthogonal ribosome competition. This Orthogonal Ribosomal Flow Model (ORFM) is proven to be stable through the use of Robust Lyapunov Functions. The optimization problem of maximizing the weighted protein translation rate by adjusting allocation of ribosomal species is formulated and implemented.