Synthetic Biology Building on Nature's Inspiration: Interdisciplinary Research Team Summaries (2010) / Chapter Skim
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IDR Team Summary 1: What new foundational technologies and tools are required to make biology easier to engineer?
IDR Team Summary 1: What new foundational technologies and tools are required to make biology easier to engineer?
Pages 7-18
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From page 7... ...
Genetic engineering began as a field more than thirty years ago and was largely developed around a set of foundational technologies that allowed researchers to amplify pieces of DNA, build relatively simple synthetic DNA elements by piecing together DNA fragments, and place those synthetic DNA elements into living systems to encode relatively simple, novel biological functions. However, the foundational technology set associated with genetic engineering does not scale readily to the engineering of large-scale integrated biological systems, such that biotechnology and medical technologies have not seen an increase in the complexity of reliably-operating biological systems that can be designed and constructed at a pace that is similar to the growth observed in other technology sectors.
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From page 8... ...
The engineering of microbial chemical factories provides important case examples of engineering complex biological systems. Researchers are successfully engineering complex metabolic pathways (comprising up to 10-20 synthetic enzymatic steps)
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Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 2006;440:940-3: http://www.nature.com/nature/journal/v440/n7086/abs/ nature04640.html.
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At the 2009 National Academies Keck Futures Initiative Conference, an IDR Team, comprising chemists, engineers, computer scientists, and others (Interdisciplinary Research Team 1A) met to identify the kinds of tools that will be needed to accelerate the design cycle of new biological systems, allowing researchers to test and execute their ideas fast and efficiently.
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From page 11... ...
Researchers already have good representations for protein structures and DNA sequences, but it is necessary to find a way to describe cellular processes and functions with equal precision. With such a description -- encompassing everything from chemical reactions in a single cell to biological interactions in a community of cells -- scientists would be able to simulate entire biological systems as well as their operations on them.
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From page 12... ...
And if unwanted change does occur, measures should be taken to ensure self-repair. The synthesized biological system should also include a sensing and diagnostic apparatus to inform us of errors that cannot be automatically corrected; just like the checkpoints included in the code of a computer program can help debug it, signals inserted at critical points in a biological circuit would reveal when and where the error occurred.
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Today, most synthetic systems rely on tinkering with natural cell components, but it would clearly be useful to create entirely artificial cells with known functionality, the paragon of synthetic biology. IDR Team Members -- Group B • J
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To determine what tools would advance such a multidisciplinary and complicated field the team decided that examining Systems Biology would be a useful starting point. Systems Biology studies complex biological systems as integrated wholes, using many different tools, including DNA sequencing, epigenetics (looking at cells that have the same genotype, but a different phenotype)
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From page 15... ...
The IDR team's goal in framing its report in terms of potential grants will encourage novel collaborations, and therefore, novel results, from scientists across many disciplines who may not currently work together. Some characteristics of new tools include cheaper and faster ways to sequence and synthesize DNA.
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Right now, synthesis costs are about $1 per base pair. • Includes methods focused on oligos on a chip, new chemistry for DNA synthesis, very long length reads, and engineering epigenetic DNA.
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5. Additional ideas In addition to discussing tools that can be used now and tools they'd like to use now, the members of the IDR team also imagined technologies that seemed a bit far-fetched, but that if made, would really help them engineer biology.
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From page 18... ...
If the scientists of the IDR team had their druthers, they would design every bit of DNA that goes into an organism so that they -- the scientists -- know exactly how it would behave now and in the future. The more tools that can make what is currently hard easy, the more quickly scientists will see rapid increases in productivity and development.
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