Standards in Synthetic Biology Workshop

By Olga Radchuk and Markus Schmidt
Biofaction
www.biofaction.com

The ST-FLOW project is a joint effort of 14 leading European research groups. It represents an important step towards the development of material and computational standards for the design of robust and predictable prokaryotic systems with the help of synthetic biology. As an emerging research-intensive discipline at the intersection of biology and engineering, synthetic biology has started to adopt approaches that will help to scale up operations previously available only as custom processes.

A workshop involving numerous stakeholders from Europe and the USA, including scientists, industry players and representatives of the major funding agencies, took place in the beginning of March at the University La Nau, Valencia. Two days, 7 sessions and 27 talks contributed towards understanding the current progress in the standardization of synthetic biology. Topics discussed during the workshop helped share up-to-date progress in the field and outlined a roadmap for standardizing biotechnology. Discussion topics ranged from regulatory frameworks to the application of the developed standards, the bottlenecks of the process of standardization, and the future of standards in synthetic biology,

Providing the synthetic biology community with standardized, freely available and properly characterized building blocks is likely one of the largest steps towards streamlining the design of synbio. Richard Kitney, from Imperial College London, presented the SynBIS platform. This system was created with the aim of facilitating the assembly of new biological parts. The platform is a registry containing data about bio parts, chasses and the associated metadata, and is able to incorporate BioCAD software. This allows for design and modeling of new devices and gene circuits using well-characterized parts. In contrast to the Biobricks foundation registry used in iGEM, which primarily has educational goals, the aim of SynBIS is to provide professional and industrial users a reliable registry with high quality content. An access policy to the new registry is still under negotiation, with a subscription-based access being most likely.

The group of Victor de Lorenzo at the National Centre of Biotechnology in Madrid, who also organized the workshop, has taken a step in the direction of open-source databases. He presented the Standard European Vector Architecture 2.0 (SEVA 2.0) database. This platform is aimed at assisting the choice of optimal genetic tools for construction of complex prokaryotic phenotypes for fundamental and biotechnological purposes. The database is linked to a material repository of vectors and constructs, which defines a general structure of a standard plasmid: a number of variable modules (an origin of replication, a selection marker and a cargo), fixed connectors that provide the reference for the whole vector layout (transcription terminators and a site for conjugative transfer), and a site to attach plasmid gadgets. Such solutions aim to significantly reduce costs for the synthesis and construction of new biosystems, as well as to increase the reliability and predictability of DNA assembly.

After shedding light on the standardization of parts, vectors and genetic circuits, Antoine Danchin, the CSO and founder for Amabiotics, reminded us that the metabolism of a host cell has a significant impact on the functioning of an externally introduced genetic circuit. Therefore, it is necessary to extend the modifications not only to the entities to be inserted in the cell, but also the host – the cellular context – itself.

Addressing this issue, Vincent Noireaux, Associate Professor at the University of Minnesota, presented another opportunity to further facilitate DNA design and modeling. His cell-free environment TX-TL platform allows for repeated prototyping with an opportunity for rapid consequent modifications, an important time-saver for the design processes. It provides an opportunity to emulate a real cellular environment in standard and controlled settings, where it is not necessary to modify the parts and circuits to fit the intermediary environment.

One element that is definitely lacking in the current discussion of standards is a consensus between research groups and centers on the necessary extent of standardization in synthetic biology. The problem of collaboration seems to be one of the most difficult unresolved issues. Jack Newman, CSO and co-founder of Amyris admitted this in his speech dedicated to the promotion of standardization and exchange of biological code. He said that the hardest task is to make people use each other’s parts, but the most impactful thing to do is to simply start using the standard.

Linda Kahl, now working with the Biobricks Foundation, reported on their experiences and strategies to increase and manage community involvement in the development, donation and uptake of standard biological parts. Their approach is modeled after the Request For Comments (RFC) process of the internet engineering task force. Allowing the community to freely exchange ideas is a prerequisite for innovation.

The availability of raw data and computational models will also have a great impact on increasing the reproducibility of biotech research results, said Michele Garfinkel (EMBO, Heidelberg). For example, asking publishers of peer review journals to provide (by default) open access for methodologies used in the research (before hitting a pay-wall) could have a real impact on standards and openness. Garfinkel also brought up a structural problem in the process of standardization; namely, the need to carry out a lot of non-novel work. Since neither scientists nor publishers have any interest in this type of work, the advancement of standardization is faced with a tough motivational challenge.

Providing a constructive environment for the community to advance the standardization process in synbio is certainly among the top priorities in order to develop biotechnology into a true engineering discipline. The joint effort of the ST-FLOW project consortium represents one important step in addressing the challenges of setting the standards in synthetic biology. In the US, the National Institute of Standards and Technology (NIST) Synthetic Biology Standards Consortium (SBSC) is also trying to move this process forward. Over the medium and long term, however, it will be necessary to internationalize the debate and development of synbio standards even further.

The ST-FLOW workshop addressed some key questions, such as what in biology can and cannot be standardized? Can highly interconnected complex systems really be standardized in the same way, as in the case in other engineering fields? What societal assumptions are behind standards, and how does intellectual property interfere with their uptake and use? How can people be inspired to contribute to the standardization process, especially when the work and efforts are privatized (no papers, no funding) and the benefits socialized (everybody will eventually benefit from established standards)?

The workshop showed that, despite progress being made, many of these questions are still under discussion. Development of synbio standards is a multi-facetted challenge that ST-FLOW, NIST and others have just started to tackle.

All views presented in this post are those of the authors and not necessarily those of PLOS.