Assay Development Platforms

Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature and to redesign existing biological systems to perform new functions. The construction de novo of large and complex genetic circuits or metabolic pathways will enable us to for example, program stem cell differentiation, detect multiple changes in cancer cells, or engineer cell factories to produce completely novel drugs or greener chemicals and biofuels. The conventional approach of engineering cells at the bench is inherently slow and expensive. Automation and industrialization reduce development time and the economies of scale of medium to high throughput processes can reduce the cost of organism development democratising the endeavour and allowing an expansion in the number of academic groups and industries that can undertake such complex organism engineering.
To realise our ambitions for synthetic biology we need enabling technologies that can not only provide robust, reliable and cost effective methodologies for the design, construction and incorporation of synthetic DNA we need to understand the interaction of the component or pathway with the host and capture holistic datasets that report back on synthetic part and pathway performance, cell growth and health.
The initial BBSRC investment (BBM00029X1 andBBM00094X1) has helped found two DNA synthesis centres, the Edinburgh Genome Foundry (EGF, based in the School of Biological Sciences) and Liverpool GeneMill (LGM, based within the Centre for Genomic Research CGR) offering DNA design, synthesis and validation of large gene constructs (up to 1Mbp). However, we need to further expand our capabilities to include high throughput assay development suited to assessing whether the DNA construct delivers the desired output (i.e. phenotype) in the host cell. Here we request support for capital equipment that will enable us to set up multi parallel medium throughput assays for cell health, function and productivity. Alongside these platforms we build the software tools for automation and analysis, together with software to integrate this data with the design and fabrication pipelines. This will provide the data needed to inform the future design of refined DNA constructs, accelerate the design build test cycle, improve efficiency and reduce the cost of application of synthetic biology applications. Ultimately this will help drive growth of the markets than can benefit from synthetic biology and add value to the initial investment in the DNA synthesis centres.

Synthetic biology has made significant strides over the past decade however, to fully realize the potential of this technology we need to be able to introduce much larger constructs to enable, for example, engineering of complete metabolic pathways or exquisite cell-control mechanisms. However, currently this requires screening a very large number of constructs to identify those that deliver the desired output. One capability missing from the arsenal of the Edinburgh and Liverpool facilities is access to automated medium throughput platforms that can swiftly screen for the desired phenotypes. This assay development capability would enable us to offer more integrated end-to-end service, help reduce the cost of delivering the desired DNA construct, and accelerate the application of synthetic biology across multiple markets.
EGF and LGM are currently automating DNA synthesis and assembly pipelines using, where possible, technology platforms that can be automated and interconnected. As the design is completely modular it can easily be expanded to include phenotype screening assays. We aim to enable the rapid design and synthesis of multiple varied DNA circuits (e.g. metabolic pathways, biosensors, counting/memory devices) and interrogate the utility of these circuits within host cell cassis via an array of assays including growth and fermentation characteristics, cell health, fluorescent reporters, RNA seq and metabolite profiling. The data generated using this battery of tests will then be processed and used to identify the best highly optimized circuits and inform design principles for the future. This vision will be achieved by adding the following screening capabilities to our already funded DNA synthesis facilities and the facilities already available at our host institutions 1. Medium throughput small volume monitored parallel cultures. 2. Metabolite screening 3. Enhanced DNA assembly platform 4. Software development.

The Edinburgh Genome Foundry and Liverpool Gene Mill will provide end-to-end design, construction and phenotypic validation of large gene constructs for academic and industrial applications. The novel tool development proposed will enable the the UK to maintain a position of leadership in Synthetic Biology. This in turn will help to attract and retain high quality researchers in the UK.
We have a broad range of good working relationships with local (e.g. Ingenza, Genabler) and international businesses (e.g. Life Technologies, Selex ES, Unilever, GSK) with an interest in synthetic biology and its application and will build on these collaborations. Importantly, our existing and developing relationships with industry partners will ensure we work alongside, rather than compete with, commercial providers while safeguarding our potential to develop Intellectual Property addressing new markets. Currently there are no companies providing DNA design and synthesis with high throughput phenotypic screening in the UK so we are not competing with industry in this arena rather we are working with industry and innovating in an area which will be of great commercial interest in the future.
Close working with Edinburgh's Research & Innovations and Liverpool's Business Gateway, the Universitys' commercialization support, we allow periodic review of the commercial potential of the technology developed in the EGF and LGM.
Societal and stakeholder engagement is considered vital to the continued emergence of SB technologies as product. We wholeheartedly recognize the importance of open communication of our research to as wide an audience as possible; both through the scientific and non-scientific press, through various media outlets including the internet and through participation at specialist and general science conferences and festivals.