This story is brought to you by our sponsor SynbiCITE, which is accelerating the commercialization of synthetic biology applications. To learn how SynbiCITE is nucleating a sustainable UK economy, visit www.synbicite.com.Perhaps better known for its International Festival, dramatic castle and royal connections, Scotland’s capital is also home to one of Europe’s fastest-growing centres for synthetic biology.The UK Centre for Mammalian Synthetic Biology (the ‘Centre’) is leading on what is, perhaps, the most underserved and challenging areas – synthetic biology for medicine and healthcare. With exciting projects on topics as wide ranging as stem cell differentiation, cell and gene therapy, and production of biologics, the Centre is working to raise the profile of Edinburgh as the leading location in Europe for research and innovation in mammalian cell engineering.The focus on mammalian synthetic biology is a natural extension of the University of Edinburgh’s reputation for world-class research into cell and stem cell biology. Professor Susan Rosser, Chair in Synthetic Biology at the University and the Centre’s Director, explains, “When planning for the Centre, I was struck by the limited number of tools that my colleagues had to work with. So much of the efforts of our Centre is centred on addressing that need.”

Creating the tools

Over the past four years, the Centre’s research team – an eclectic community drawn from all corners of the University – have helped to create a “tool box” for cell biologists. For example, Professor Steven Pollard, based at the Scottish Centre for Regenerative Medicine (SCRM), has built a library of synthetic transcription factors that can nudge adult stem cells into neurons. Prof Rosser is creating ‘safe-harbour’ landing pads in chromosomes for stable, predictable and tuneable transgene expression. Professor Bill Earnshaw, from the Wellcome Centre for Cell Biology, is constructing human artificial chromosomes (HACs) to study the process of cell division. HACs can also carry large payloads of DNA suited for correcting genetic defects or engineering predesigned complex traits in cell lines. A database of drug-responsive protein sequences (SynPharm) derived from the IUPHAR/BPS Guide to Pharmacology, created by the lab of Prof Jamie Davies, Biomedical Sciences, is coming in handy for researchers wishing to introduce a level of drug-control into their synthetic circuits.

Building applications

With the toolbox now full of clever new devices, research is turning towards their deployment in ever more complex and sophisticated applications. The Centre has commenced work on turning cells into biosensors for drug discovery, engineering cells to self-assemble into complex patterns and structures suited towards tissue engineering, and even rewiring cells to be better cell therapies (in the latter case by Dr. Tilo Kunath of the SCRM for treatment of Parkinson’s Disease). “Word is now out that we can offer a suite of tools that not only help researchers gain new biological insights but also have commercial applications,” says Prof. Rosser. “That’s started to generate some really exciting and often unexpected conversations and collaborations.”

Technology driving research

The Centre’s technology platforms – which span the entire “design-build-test-learn” paradigm of biological engineering – have demanded the attention of many researchers. The flagship facility is the Edinburgh Genome Foundry (EGF), which is a fully automated and integrated DNA design and assembly platform (‘build’) and a sister facility to those based at Imperial College London (The Foundry), University of Liverpool (GeneMill) and at the Earlham Institute in Norwich (Earlham’s DNA Foundry).

One of the largest and most fully automated in Europe, the EGF offers fee-for-service design and assembly of DNA up to chromosome length. It has automated many of the most tedious lab procedures such as plasmid preparation and colony picking. In “test,” the Centre has access to gene sequencing, proteomics and metabolomics, and in “learn,” a wide variety of models of systems are available. While not limited to assembly of mammalian constructs, the EGF is specializing in mammalian synthetic biology and is building a registry of parts aligned with the EMMA (Extensible Mammalian Modular Assembly) methodology developed at Edinburgh.The EGF is helping researchers to change the way they think about and do research. A growing community within Edinburgh are waking up to the potential of automation and high-throughput DNA assembly. Dr Hille Tekotte, the EGF manager, says, “We are fortunate to have some unique platforms that are simply not affordable for most labs – whether in academia or industry. So we are open for business to all.”The Foundry is also developing software for computer aided design (CAD) of DNA, computer aided manufacturing (CAM) of DNA, and data analysis. The software team delivered 28 software packages during 2017, and many of these, valuable for all aspects of molecular biology, are open access and can be downloaded from the Foundry website.

Innovation fast track

One of the many remits of the six UK Centres for synthetic biology, funded through the UK Government’s Synthetic Biology for Growth Programme, was to fast track innovation and generate new business opportunities and jobs. “Clearly, mammalian synthetic biology research is further from the market than other applications but it definitely has attracted the attention of industry,” says Prof. Rosser.Over the past four years, the Centre has hosted visits from over 40 companies and has ongoing collaborations with several. It is actively seeking new opportunities to engage with business, to understand their needs, and to identify opportunities for working together. The University was a founding partner of SynbiCITE and the Industrial Biotechnology Innovation Centre (IBIOIC: HQ in Glasgow, Scotland), both of which have assisted with grant funding to ‘oil the wheels’ of exciting new collaborations and access to industry and investor networks. The Centre is working closely with SynbiCITE to ensure that the UK can maintain its past success in synthetic biology research and translate this into economic benefits through innovation and commercialization.Indeed, the Centre hopes to spin out its own technologies and help build a local cluster of synthetic biology startups. The Edinburgh region is already home to three UK synthetic biology SMEs – Synpromics, Ingenza, and Biotangents – that are all partners. The Centre has an active programme of training and development for its early career researchers. Dr Liz Fletcher, the Centre’s manager, says, “We now have momentum in our research programmes and outputs that I can see being commercialized in the near future. We also have an enthusiastic band of budding entrepreneurs. So watch this space!”

Building a new biology

Synthetic biology is a strategic research theme for the University of Edinburgh, which has made a significant investment in talent, training, and facilities in the field over the past decade. The School of Biological Sciences, one of the top five schools in the UK and the HQ for the Centre, is currently exploring the option of establishing a biotech research hotel and incubator as part of its £120M estates redevelopment. “We felt there was a gap in local provision for space that is embedded within an intellectually stimulating environment and also in close proximity to state-of-the-art equipment and the necessary expertise to use it,” says Prof. David Gray, Head of the School of Biological Sciences. The idea is supported by IBIOIC and Scotland’s economic development agency, Scottish Enterprise, both keen to grow the synthetic biology cluster in the Edinburgh region and Scotland.Indeed, the Centre has worked hard to raise the profile of the Scottish synthetic biology community. It has hosted many high-profile international meetings, including two SynBioBeta Activate events (the first to be held in Scotland), a meeting of the International Synthetic Yeast Chromosome Sc2.0, and numerous other synthetic biology streams in larger society conferences. The Centre also works hard to engage the public, schools, policy makers, and regulators in its research to ensure that the work we do courts conversation and not controversy. Most exciting are plans to host the very first Mammalian Synthetic Biology Workshop (historically only hosted by MIT in Boston) in Europe in 2020, putting Edinburgh ever more firmly on the international map for synthetic biology.Edinburgh has had a long and illustrious history of game changing research in the life sciences. It was the birthplace of epigenetics, the first recombinant Hepatitis B vaccine, and the first cloned animal, Dolly the Sheep, now proudly on display in the National Museum of Scotland. Synthetic biology will enable Edinburgh to extend that list of biotech-based breakthroughs in areas such as gene and cell therapy, synthetic vaccines, drug discovery, and diagnostics.You can find out more about our Centre at www.synbio.ed.ac.uk or follow us on twitter @SynthSysEdThe Centre is currently looking to recruit some new team members, if you are interested please visit our site to find out more http://www.synbio.ed.ac.uk/vacancies