Special Issue: Manifesting Synthetic Biology

Manifesting synthetic biology Ernesto Andrianantoandro (Editor) Trends in Biotechnology

Synthetic biology has eluded precise definition since its early days at the turn of the 21st century. At its heart are the goal of engineering biology to control living systems and the practice of assembling a synthetic system from component parts. However, the boundaries of synthetic biology as a discipline are hazy. It is difficult to gauge its success until one examines how it manifests itself in other fields. Although not commonly branded as such, the fields of protein engineering, optogenetics, and genome editing all participate in synthetic biology (they are part of synthetic biology and synthetic biology is part of them). This special issue of Trends in Biotechnology begins with a Letter by Bijan Zakeri and Peter Carr on the limits of synthetic biology. They explore the evolutionary limits of reliability in synthetic biology and propose a ‘Relative Evolutionary Scale’ to gauge the robustness of modifications made to engineered organisms. Next, a Letter by Arash Kianianmomeni on UVB-based optogenetic tools looks forward to a future in which a suite of photoswitchable proteins can be used for multiplexed control of engineered cell behavior. The impact of engineered organisms on policy, society, and even at the dinner table is explored in a Science and Society article by Chidananda Nagamangala Kanchiswamy and colleagues on the possibility of genetically edited fruit crops. They suggest that the accepted notion of genetically modified organisms (GMOs) is called into question by the advent of genome-editing technologies. Two Feature Review articles provide comprehensive overviews of engineering principles being applied to complex biological systems. The immune system and the brain represent two unique frontiers for synthetic biology. Martin Fussenegger and Barbara Geering discuss an engineering approach to modulating the human immune system. This ranges from protein engineering of key effector molecules to genetically engineering immune cells for autologous cell therapy and adoptive immunotherapy. These approaches embrace the spirit of synthetic biology at multiple levels and, when considered in combination, offer the possibility of an incredible degree of control over the immune system as a whole. Yong Ku Cho and Daniel Schmidt discuss the mechanism of action of natural photoreceptor systems and the design principles for engineering these core components for optogenetics. Given the natural modularity of optogenetic systems, this provides an ideal exCorresponding author: Andrianantoandro, E. ([email protected]). 0167-7799/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2014.12.002

ample of how to build a synthetic biological ‘part’. In addition to surveying a host of light-controllable proteins in detail, they discuss the challenges faced when using optogenetics to study the brain. In a Review that takes the discussion of optogenetics further, Bianxiao Cui and Kai Zhang examine advances in optogenetic control of cellular signaling. They outline the variety of cellular functions that can be controlled with optogenetics, and explain how such a fine degree of spatial and temporal control can be achieved by optogenetic systems. Viktor Stein and Kirill Alexandrov extend the discussion of engineering artificial signaling systems to include other inputs, and survey protein switches with a variety of architectures and mechanisms of action. Interfacing synthetic protein switches with the appropriate cell function outputs will allow independent, parallel circuits to operate in cells. Domitilla Del Vecchio delves deeper into circuit design and explores the concepts of modularity, insulation, and context-dependence, using examples from protein-based and genetic circuits. Even well-characterized modules may not function as intended when they are connected. This can be due to the ‘context’ surrounding a module. Modules can impinge on each other in ways that affect signal output, and sharing cellular resources can also have a detrimental effect. Insulating modules from context will be crucial to future engineering strategies. Another major concern is how to deploy synthetic circuits in organisms. Even protein-based circuits must enter host cells as genetic information. Genetic modification is a cornerstone of synthetic biology and has been revolutionized by genome-editing techniques. Daniel Voytas and Nicholas Baltes review the application of genome editing to synthetic biology in another frontier area: plants. The synthetic circuits deployed through genome editing could comprise inserted exogenous genes, modified endogenous genes, or modified nucleases with transcriptional activation or repression domains to control gene expression with precision. To close out the issue, Matthew Porteus and colleagues enlighten us on one of the most important issues associated with genome-editing efforts: quantifying on- and off-target activity of the nuclease employed. Given the recent excitement surrounding the use of genome-editing tools to modify cells, reliability and widespread adoption of the tools will depend on knowing whether the genome has been modified only as intended. The reviews in the first half of the issue delineate the explosive growth in the number of parts now available for protein-based circuits, as well as the increasing sophistication of the types of inputs used to control cellular pathways. Protein-based circuits offer tremendous advantages in Trends in Biotechnology, February 2015, Vol. 33, No. 2


Editorial speed and efficacy over genetic circuits, and proteins will likely be the effector molecules of the future. Cellular signaling plays a key role in the utility of protein-based circuits – virtually all cell behaviors can be controlled through the appropriate signaling network. In the second half of the issue, we can see how circuit design and the methods for genetic modification of organisms and control of gene expression have also grown in sophistication. Despite the increasing impact of synthetic biology across research areas, many issues need to be resolved. The acceptance and adoption of synthetic biology technologies and their potential


Trends in Biotechnology February 2015, Vol. 33, No. 2

impact on society must be addressed. Fundamental challenges in engineering and design also remain. Modularity, context-dependence, reliability, and robustness to evolution are essential conceptual building blocks for the guiding principles of synthetic biology. This spirit could operate in areas where least expected. It may become the case that all forms of biological research will one day have a strong synthetic biology component, either as a means or as an end. I hope you all enjoy reading this special issue, and I welcome your comments and ideas; feel free to contact us with any feedback or questions at [email protected]

Manifesting synthetic biology.

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