Model-Based Design of Molecular Systems - NCCR MSE

Model-Based Design of Molecular Systems

Example for rational-model based design. A digital signal processing circuit with four inputs (a-d, left) was automatically designed using logical gates and signal carriers such that the output (right) establishes a pre-defined logical computation on the input signals (Figure from Marchisio & Stelling, PLOS Comp. Biol.7: e1001083, 2011).
Example for rational-model based design. A digital signal processing circuit with four inputs (a-d, left) was automatically designed using logical gates and signal carriers such that the output (right) establishes a pre-defined logical computation on the input signals (Figure from Marchisio & Stelling, PLOS Comp. Biol.7: e1001083, 2011).

In the design of biological systems (synthetic biology), the aims range from detailed model-based design of novel systems to general concepts for the rational and – potentially automatic – design of large-scale circuits.

Robust systems designed to enable the use of engineered molecular systems in biotechnological and medical applications are of particular interest. This project will address various aspects of methods and model development for Molecular Systems Engineering to enable rational (model-based) design of molecular systems and component features such as kinetic parameters in iterations with experimental (analysis) approaches.

For the rational design of synthetic molecular systems, mathematical models of different types have been developed. While a growing number of computational design tools implements such formal approaches, major challenges remain, for example, in terms of systematic model development and in the rational design of informative experiments for systems characterization.

In the area of model-based analysis and design of genetic circuits, the development of computational models and design methods will enable rational design of parts and circuits. Another focus on the design of engineered metabolic networks will support molecular engineering of complex biosynthetic and energy-producing systems by integration from molecular modules to factories.

Publications

E. Karamasioti, C. Lormeau, J. Stelling “Computational design of biological circuits: Putting parts into context“ Mol. Syst. Des. Eng. 2017. [DOI]
M. Xie, H. Ye, H. Wang, G. Charpin-El Hamri, C. Lormeau, P. Saxena, J. StellingM. Fussenegger “β-cell–mimetic designer cells provide closed-loop glycemic control“ Science 2016, 354:1296-1301. [DOI]
R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability“ ACS Synth. Biol. 2016, 5:1098-107. [DOI]

Project Leader

Jörg Stelling

Persons involved

Claude Magnard
Asli Azizoglu

Lab

Stelling group @D-BSSE