Jean Peccoud and colleagues at the Virginia Bioinformatic Institute have published their work analysing one of the clone banks derived from the BioBrick registry of parts for synthetic biology.
What they found reflects the way in which the registry has grown, particularly the ready-made clones. Peccoud and his team argues that future registries will have to pay closer attention to what the concept of a 'part' means in synthetic biology as the current definitions do not necessarily work all that well.
The VBI researchers see registries such as the BioBrick Foundation's as "complementary to de novo synthesis since both approaches can be used to fabricate designer DNA sequences".
When he spoke at BioSysBio earlier this year, Peccoud said there is a role for many types of registry. Some will be kept inhouse by companies to allow them to include their own parts. Others will tend to use publicly available libraries.
The typical structure of a BioBrick part includes a promoter, a ribosome binding site, a coding sequence and a transcription terminator. To go into the BioBrick Registry, the parts must have a prefix and suffix sequence as well. These are restriction enzyme sites that allow a generic cloning process to be used to combine BioBrick parts – as long as the restriction-site sequences are not in the sequences of either of the parts. Work is continuing in the BioBrick Foundation on ways to streamline the process of stitching together parts from different parts of the database. And those composite parts can themselves be placed in the Registry.
By July 2007, the BioBrick Registry had close to 5000 entries. Of them, almost a thousand were available as bacterial clones, produced primarily by the student teams competing in the iGEM contest. Perhaps because of the ad hoc nature of competitions, the parts in the clone library that VBI worked with
"The implementation of a workable abstraction hierarchy remains problematic...Some part sequences even include designs, a higher level in the abstraction hierarchy. These observations result from the lack of consensus in the community on how biological parts should be defined. Nothing illustrates this confusion better than the complex architecture of promoters.
"On the one hand, promoters are generally considered as parts but on the other hand they have well-characterised domains that can be associated with specific functions."
What they mean here is that promoters can bind to a number of different transcription factors, each of which control the activity of the target gene. Which binding sites matter depend on the organism the part is cloned into. Some will have a given transcription factor; others will not. It's another limit on the effective modularity of synthetic biology components.
They conclude: "The idea of developing collections of standardised parts is a transformative idea in biology. After a few years of a large-scale experiment, it becomes apparent that developing and managing this new type of resource for synthetic biology raises a number of original questions."
The focus is now going to move from the idea of building a library of parts to what structure that library should take.
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