Population Design for Synthetic Gene Circuits


Date

2021

Publication Type

Conference Paper

ETH Bibliography

yes

Citations

Altmetric

Data

Abstract

Synthetic biologists use and combine diverse biological parts to build systems such as genetic circuits that perform desirable functions in, for example, biomedical or industrial applications. Computer-aided design methods have been developed to help choose appropriate network structures and biological parts for a given design objective. However, they almost always model the behavior of the network in an average cell, despite pervasive cell-to-cell variability. Here, we present a computational framework to guide the design of synthetic biological circuits while accounting for cell-to-cell variability explicitly. Our design method integrates a NonLinear Mixed-Effect (NLME) framework into an existing algorithm for design based on ordinary differential equation (ODE) models. The analysis of a recently developed transcriptional controller demonstrates first insights into design guidelines when trying to achieve reliable performance under cell-to-cell variability. We anticipate that our method not only facilitates the rational design of synthetic networks under cell-to-cell variability, but also enables novel applications by supporting design objectives that specify the desired behavior of cell populations.

Publication status

published

Book title

Computational Methods in Systems Biology. CMSB 2021

Volume

12881

Pages / Article No.

181 - 197

Publisher

Springer

Event

19th International Conference on Computational Methods in Systems Biology (CMSB 2021)

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

Cell-to-cell variability; Synthetic biology; Computer-aided design

Organisational unit

03699 - Stelling, Jörg / Stelling, Jörg check_circle

Notes

Funding

Related publications and datasets

Is cited by: