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This is the second volume of the recently launched series of periodical reports that cover recent developments in synthetic biology. Synthetic biology is a relatively new research area which combines biology and engineering to design, build and test biological systems. The definition of synthetic biology has evolved into a more purposeful term of engineering biology: the synthesis of complex, biologically based (or inspired) systems, which display functions that may not exist in nature. Engineering is at the heart of synthetic biology, being applied at all levels of biological hierarchy from individual molecules to cells, tissues and organisms. There is a rapidly growing body of literature for synthetic biology, with several specialist journals now available. Finding the most appropriate information in this field can be time-consuming. Therefore, this series aims to offer comprehensive reviews of recent literature in themed chapters. Each chapter strives to highlight the most recent findings in specific sub-areas and reviewes research reports that were published over the last two to three years. Revisions of traditional concepts in the light of emerging discoveries are also provided by each chapter, which differentiates this series from other publications, while keeping with the progress without losing touch with foundations.

The volume starts with an overview of synthetic information processing circuits (Lonzaric, Fink and Jerala). Conducive to one of the fundamental topics in synthetic biology, synthetic circuits are also one of the most rapidly evolving concepts. The chapter takes a brave step towards highlighting challenges of developing circuits in mammalian cells. Approaches to design logic circuits using genetic elements from bacteria, yeast and plants are discussed on par with strategies used to re-wire signalling pathways that are endogenous to mammalian cells. Externally responsive systems, circuits combining transcription and translation and circuits with recombination are featured in detail, providing a critical focus on use in applications including personalised cell therapies. A logical continuation of this topic is offered in the next chapter, which outlines new avenues in synthetic biology modelling (Milano, Marzuoli, Lorenz and Fraternali). Synthetic biology operates with biomolecular ensembles resulting from the assembly of different components in varied combinations. To be effective in routine use in industry, these ensembles will benefit from accurate computational models that can ultimately pave the way to digital bio-manufacturing. This forms the subject of the review that screens for a means of modelling native and non-native assemblies, by matching force-field parameterisations with conformational flexibility of multi-partner subcellular and virus-like assemblies. Often referred to as a bottom-up synthetic biology, this approach of using biomolecular assembly to construct discrete and functional higher-order structures is gaining momentum in formulating the tool box of molecule-specific scaffolds. This stream of research is further detailed in the following chapter, which reviewes protein scaffolds designed to control signalling or metabolic activity in living cells (den Hamer, Rosier, Brunsveld and Greef). The chapter goes through a rich repertoir of multi-component protein complexes involved in signal transduction, which are complemented with mathematical models of scaffold assemblies and signalling pathways these scaffolds regulate. Computational predictions of signal ihibition and amplification are described with reference to experimental evidence. The chapter concludes with examples of synthetic scaffolds for signalling networks and metabolic engineering which are of relevance to commercial applications. Following the design of intracellular scaffold proteins, the fourth chapter outlines computational design rules for synthetic symmetrical proteins (Vrancken, Wouters, Mylemans, Noguchi, Tame and Voet). This report takes a somewhat different approach for synthetic biology designs starting from protein folding motifs, bottom, to geometrically defined proteins, up, assembled according to a desired symmetry. Consensus designs that rely on repeated motifs constitute a mainstream trend of the chapter. Two types of exciting case studies are given including repeat proteins delivering specific functions and distinguishable protein folds based on the conventional classification, e.g. β-propeller, α/β-barrel and the like. The progress in designing de novo proteins computationally is followed in the penultimate chapter that gathers information about experimentally validated designs (Ryadnov). This chapter discusses how the current understanding of protein structure-activity relationships may be improved by creating particular biological functions with designer synthetic biomaterials ranging from artificial viruses to cell-supporting extracellular matrices. The latter is taken to the level of one of the most challenging therapeutic targets in the closing chapter of the volume (Spaans, Bax, Bouten and Dankers). This report reviews top-down and bottom-up approaches used to emulate the native extracellular matrix with synthetic analogues for the treatment of myocardial infarction. The impact of such matrices on tissue remodelling, cardiac performance and repair is discussed in line with therapeutic routes including injectable scaffolds, cell delivery and recruitment and the stimulation of endogenous repair. The chapter completes the volume compiled in the spirit of multiscale synthetic biology, starting from genetic elements and culminating with applications at the organismic level of biological organisation.

Each themed chapter is structured around current trends in the reviewed area, providing the authors’ outlook of future perspectives, either as a separate section or incorporated in the text. All chapters are written by leading researchers in their subject areas allowing for a broad appeal to researchers in academia and industry.

Maxim Ryadnov, Luc Brunsveld and Hiroaki Suga

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