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UK Opening Five New DNA Synthesis Foundries to Support National Research

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NEW YORK (GenomeWeb) – British scientists will soon have access to five new facilities for synthesizing DNA, an emerging national resource that will support genomics research.

The DNA foundries have been funded through an £18 million ($23.5 million) investment from the UK's Biotechnology and Biological Sciences Research Council and should become fully operational by next year, according to a BBSRC representative.

Ceri Lyn-Adams, strategy and policy manager for the agency, which supports UK academic life sciences research, told GenomeWeb that foundries have been established at the University of Edinburgh, the Earlham Institute in Norwich, Imperial College London, the University of Liverpool, and the MRC Laboratory of Molecular Biology in Cambridge.

In addition, as part of the same investment, funding was made available to back collaborative projects with all of those institutes and partners at the University of Oxford, the University of Bristol, the University of Southampton, and the University of Birmingham.

According to Lyn-Adams, the capital investments in DNA synthesis were made as part of the country's Synthetic Biology for Growth Program to bolster the UK's synthetic biology capabilities. The undertaking dates back to the British government's 2012 Autumn Statement, which allocated £50 million to support synthetic biology as a priority technology. While the initial financing for the foundries goes back four years, most are now in the process of bringing their DNA synthesis equipment online, with the aim of becoming fully operational in 2017.

Hille Tekotte, manager at the Edinburgh Genome Foundry, said that the EGF, which announced its opening in July, is already producing DNA.

"We have assembled DNA and we are assembling DNA, but we have to optimize quite a few sets before we go into full production, hopefully by the start of next year," Tekotte told GenomeWeb.

EGF aims to provide clients with end-to-end design, construction, and validation of gene constructs of up to 1 megabase pairs. The facility is officially directed by Susan Rosser and Patrick Cai. Because of its automated setup, it is has been referred to as the UK's flagship DNA foundry, with a variety of applications envisioned. Tekotte said that most of the projects discussed so far have been in mammalian genomics, though the facility plans to also specialize in assembling yeast genomes. Cai, for instance, is the coordinator of the international Synthetic Yeast Genome Project.

"We are a university facility and it is likely that our first customers here will be university researchers, especially because we have a biology research center here," she said. "Once we get up to bigger capacities with the fully automated system, we should be able to take on other customers."

EGF's setup consists of a variety of robotic assembly methods and instruments. The foundry also offers cell phenotyping assays, including mass spectrometry, quantitative PCR, and high-through microfermentation. Together with San Francisco-based Autodesk, EGF developed Genetic Constructor, a web-based tool for designing large DNA constructs and combinatorial libraries. This allows users to import genomic pieces from existing registries or order their constructs from the EGF. Users can then organize these constructs into composable blocks.  

Larry Peck, senior director of Autodesk's bio/nano group, told GenomeWeb that the tool will allow EGF and other foundries to access DNA manufacturing capabilities that "once only existed behind industrial walls." He noted that Genetic Constructor has been made freely available, meaning that foundries in other countries have access to this "top notch front-end design tool."

Tekotte said that EGF has offered Genetic Constructor since it officially opened in July.

Another foundry to officially open over the summer was the Earlham Institute's DNA Foundry. The resource is housed at the Norwich Research Park and was specifically funded to support the design, generation, and exploitation of high-value compounds and bioactives obtained from plants, microbes, and animals, according to its website.

EI's DNA Foundry is also part of the UK's National Capability on Genomics, meaning that it will be complemented by EI's existing suite of Illumina and Pacific Biosciences next-generation sequencing instruments. Specifically, EI has said it will offer NGS-based construct validation for high-throughput assembly projects.

"We're currently able to perform high-throughput, parallel-DNA assembly at nanoscales and move directly to verification by sequencing," said Nicola Patron, leader of EI's new synthetic biology group. Patron said that EI is currently developing automating protocols and workflows for use with plants, algae, and microbial cells to complete design-build-test synthetic biology workflows.

EI was previously known as the Genome Analysis Center (TGAC) until it was renamed in June.

Patron added that EI is looking to make its resources available to academics and industrial partners working in the area of plant and microbial synthetic biology and biotechnology. Some internal projects include applying new Cas9/CRISPR genome editing methods to improve crop yield, and developing plants for use as production systems for therapeutic molecules.

In addition to EGF and EI, the other three foundries funded through the UK's Synthetic Biology for Growth Program have already been officially opened or are in the process of launching. Paul Freemont, head of structural biology at Imperial College London, told GenomeWeb that the new London DNA Foundry was opened in April and became operational over the summer.

Services in development include bio-computer-assisted design (Bio-CAD), automated genome assembly, genome editing and construction, and protein and cell engineering, among others. Freemont noted that the London DNA Foundry is providing services to both academic and industry partners, and is currently "running projects across both customer bases."

However, unlike EGF, which is currently focused on serving university researchers, or EI, which emphasizes plant and microbial genomics, the London DNA Foundry is more focused on providing its services to startups, small- and medium-sized enterprises, and multinationals. Freemont noted that the London DNA Foundry is collaborating with EGF on sharing approaches for large-scale assembly of DNA to synthesize whole chromosomes.

Looking ahead, Freemont said that the London DNA Foundry aims to achieve a “cloud laboratory,” where researchers will be able to design biological systems, rather than implementing them in experiments. Designs could be sent across the cloud to the foundry, and shipped back, allowing a "fully automated and integrated research environment for synthetic biology based in the cloud."

The London DNA Foundry also aims to scale up its infrastructure to support "biofactories" based on its platforms, Freemont said, underscoring that his foundry, like others, will continue to develop and offer new services and resources over time.

Representatives for the Liverpool GeneMill and the Synthetic Biology Facility at MRC Laboratory of Molecular Biology did not respond to requests for comment. According to BBSRC's Lyn-Adams, the Liverpool GeneMill, headed by Mark Caddick, will offer a high-throughput, automated workflow for synthesizing DNA for bacteria, fungi, plants, and mammalian cells, while MRC's facility, headed by Hugh Pelham, will provide a robotic platform to automate assembly of short DNA fragments into expressible genes, including the picking, growth, and analysis of DNA from bacterial colonies.

Freemont and Patron both noted that the five foundries have already set up an informal network dubbed the Foundry Forum to discuss best practices and agree on new processes and protocols.

"We are in the early stages of exploring how the BBSRC-funded foundries can work together on research projects to benefit biotechnology and synthetic biology communities, both academic and in industry," Patron said. She noted that each foundry will continue to specialize, with the overarching goal of supporting the UK's bioeconomy. "Here at EI, we are focusing on the wider strategic objectives in food security, industrial biotechnology, and human health," she said.

Freemont said the first foundries-wide meeting was held at ICL this month and a second is planned to take place in Edinburgh in November.

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