Synthetic modular systems – reverse engineering of signal transduction

  title={Synthetic modular systems – reverse engineering of signal transduction},
  author={Tony Pawson and Rune Linding},
  journal={FEBS Letters},

Systems biology meets synthetic biology: a case study of the metabolic effects of synthetic rewiring.

This work combines high-throughput proteomics with the MMG probabilistic tool, which integrates the data with the metabolic circuit's topology to study the global metabolic effects of the insertion of synthetic circuits in a cellular chassis.

The promise of synthetic biology

  • J. Pleiss
  • Biology, Engineering
    Applied Microbiology and Biotechnology
  • 2006
The design concept and examples from four fields of application (genetic circuits, protein design, platform technologies, and pathway engineering) are discussed, which demonstrate the usefulness and the promises of synthetic biology.

Designing new cellular signaling pathways.

Systems and Synthetic Biology in E. coli Cells Quantitative System Characterization, Programming and Engineering Novel Cellular Functions

The work showed that the level and variability of gene expression varied across different cell strains, and it suggested that gene circuit modules from a standard library cannot be used universally; the cellular context and the time dependent dynamics must be considered when implementing gene circuits.

Peptide and protein building blocks for synthetic biology: from programming biomolecules to self-organized biomolecular systems.

This work describes how, for certain protein-folding motifs, polypeptide chains can be instructed to fold and combined to give structured complexes, and how protein-based systems may be encapsulated to control and investigate their functions.

Overview of Signal Transduction

An overview of common features of cellular signaling pathways, including their interactions and responses to environmental stimuli, focuses on the regulation of signaling pathways by protein functional‐domain interactions as well as the intracellular proteins that mediate signal transduction.

Designing biological systems.

The scientific accomplishments in synthetic biology are described, as well as its forays into biological part standardization and education of future biological designers.

Reconstruction of genetic circuits

Recent progress in this area of synthetic biology is described, highlighting newly developed genetic components and biological lessons learned from this approach.

Rule-based modeling of biochemical systems with BioNetGen.

This work focuses on how a rule-based model is specified in the BioNetGen language (BNGL) and how a model specification is analyzed using the Bio netGen software tool.

Rules for Modeling Signal-Transduction Systems

Approaches to creation of mathematical models of signaling systems with strategies that keep the models from being unwieldy but still allow them to accurately reflect biological systems are reviewed.



Reprogramming Control of an Allosteric Signaling Switch Through Modular Recombination

This work engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the “output” domain of N- WASP was recombined with heterologous autoinhibitory “input” domains to facilitate the evolution or engineering of cellular signaling circuits.

Assembly of Cell Regulatory Systems Through Protein Interaction Domains

The sequencing of complete genomes provides a list that includes the proteins responsible for cellular regulation. However, this does not immediately reveal what these proteins do, nor how they are

Engineering stability in gene networks by autoregulation

Simple gene circuits consisting of a regulator and transcriptional repressor modules in Escherichia coli are designed and constructed and the gain of stability produced by negative feedback is shown.

Programmable cells: interfacing natural and engineered gene networks.

This work employs a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: the SOS signaling pathway responding to DNA damage, and a transgenic quorum sensing signaling pathway from Vibrio fischeri.

A partnership between biology and engineering

Any body of theory and experimental capability that enables quantitative prediction of a system’s behavior will be applicable to synthetic biology in that it will enable prediction of the behavior of human-designed biological artifacts before those are instantiated in DNA code.

Combining biological networks to predict genetic interactions.

Experimental evidence demonstrated the reliability of the predicted pairs of SSL genes in Saccharomyces cerevisiae by using probabilistic decision trees to integrate multiple types of data, including localization, mRNA expression, physical interaction, protein function, and characteristics of network topology.

Optimization of specificity in a cellular protein interaction network by negative selection

It is shown that an isolated peptide ligand from the yeast protein Pbs2 recognizes its biological partner, the SH3 domain from Sho1, with near-absolute specificity, suggesting that system-wide negative selection is a subtle but powerful evolutionary mechanism to optimize specificity within an interaction network composed of overlapping recognition elements.

Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion

Positive feedback is used to construct a synthetic eukaryotic gene switch in Saccharomyces cerevisiae that resembles analog–digital conversion and has implications for understanding the graded and probabilistic mechanisms of enhancer action and cell differentiation.