Synthetic biologists will feed DNA building blocks into a robotic factory called the GeneMill, which will automatically weave them into custom-designed genetic constructs. The problem is that building artificial DNA sequences—the raw material for synthetic biology—remains slow, expensive, and error-prone. Most researchers lack the equipment or expertise to assemble long, high-fidelity DNA constructs themselves. The GeneMill aims to remove this bottleneck by automating the entire fabrication pipeline, from design to quality control. If successful, the GeneMill will give researchers cheap, rapid access to reliable DNA parts. This could accelerate fundamental science—for example, genome-scale engineering and protein expression prototyping—by letting scientists focus on design and testing rather than manufacture. In the longer term, cheaper DNA construction could speed up the development of engineered microbes that produce medicines, biofuels, or industrial chemicals, and improve biosensors for environmental monitoring or medical diagnostics. The project is primarily a technology platform, not a direct application. But by making DNA fabrication as routine as ordering a custom electronic circuit, it could transform how quickly and cheaply synthetic biology advances.
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Synthetic biology is an emerging field that has been described as the construction of artificial biological devices, pathways or networks or the re-engineering of existing ones. Key to this engineering process is the construction of parts or components, which are encoded in DNA. A limiting factor in synthetic biology is access to cheap, high-fidelity DNA constructs encoding the components. This proposal is to fund the Liverpool GeneMill, which will take in raw materials in the form of DNA blocks and long oligonucleotides (Ultramers) and together with pre-existing blocks and DNA stretches from biological material, weave these into high fidelity DNA constructs. This in turn will be used for genome-scale engineering and protein expression prototyping. This will be achieved through robotic automation of a manual pipeline. Alongside the fabrication of constructs will sit a DNA computer-aided design tool, developed to fit with our pipeline. We will develop this in collaboration with a software development company (Genome Compiler), linking users with a components database and taking designs and converting this into manufacturing blueprints for the GeneMill. This will in turn link into a laboratory management system, allowing individual tracking, quality control of each project as it moves through the GeneMill. Ultimately the GeneMill will provide a rapid, cost-effective and accessible fabrication facility for DNA parts. By removing the complexity of manufacture for the user, GeneMill will allow researchers to focus on the design and testing of the parts, devices, pathways and networks.
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