TY - JOUR
T1 - Mediating Ribosomal Competition by Splitting Pools
AU - Miller, Jared
AU - Al-Radhawi, M. Ali
AU - Sontag, Eduardo D.
N1 - Funding Information:
Manuscript received August 28, 2020; revised October 26, 2020; accepted November 15, 2020. Date of publication November 30, 2020; date of current version December 22, 2020. This work was supported by the NSF under Grant 1849588 and Grant 1716623. Recommended by Senior Editor M. Arcak. (Corresponding author: Eduardo D. Sontag.) Jared Miller and M. Ali Al-Radhawi are with the Department of Electrical and Computer Engineering, Northeastern University, Boston, MA 02115 USA (e-mail: miller.jare@northeastern.edu; malirdwi@northeastern.edu).
Publisher Copyright:
© 2017 IEEE.
PY - 2021/11
Y1 - 2021/11
N2 - 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 letter, 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.
AB - 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 letter, 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.
KW - Synthetic biology
KW - orthogonal ribosome flow model
KW - robust Lyapunov functions
KW - translation rate optimization
UR - http://www.scopus.com/inward/record.url?scp=85097374002&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097374002&partnerID=8YFLogxK
U2 - 10.1109/LCSYS.2020.3041213
DO - 10.1109/LCSYS.2020.3041213
M3 - Article
AN - SCOPUS:85097374002
VL - 5
SP - 1555
EP - 1560
JO - IEEE Control Systems Letters
JF - IEEE Control Systems Letters
SN - 2475-1456
IS - 5
M1 - 9273048
ER -