Protein Modules Consortium & Synthetic Biology

I have become a member of the Protein Modules Consortium, along with all participants in the FEBS course on modular protein domains that I attended recently. The aim of the consortium is the "promotion of scientific knowledge concerning the structure and function of protein modules, as well as the dissemination of scientific knowledge acquired by various means of communication".

Modular protein domains are "parts" inside a protein that can be regarded as a module. In this sense one could try to understand the function of a protein by understanding how the modular parts behave in the context of the whole protein. Another useful interpretation is that one should be able to create a database of modules that we can understand and create proteins with a predetermined function by copying and pasting the parts in the right way. Here are two short reviews on the subject. What would be the most efficient way of creating a database of protein parts that can be combined ? They should all be cloned into the vectors in the same way and there should be already tested protocols to rapidly combine the parts together. One of the future goals of the consortium, that was discussed in the FEBS course, is exactly to promote a set of cloning standards that could be used to this effect.

One possible strategy would be to use the Gateway cloning system. This is an in-vitro cloning method that is used for example by Marc Vidal's lab in the orfeome project of C. elegans. It is a reliable system , specially for small protein domains, and it is very fast. Compared to traditional cloning strategies it could be a bit more expensive but not much more if you consider the cost of the restriction/ligase enzymes. Creating an "entry" vector can be done with a PCR reaction followed by a recombination reaction (~2h) (followed by the usual transformation and sequencing steps) and this entry vector could be then stored in the databank. The biggest disadvantage mentioned for this cloning strategy is the reported low efficiency in cloning big proteins, but this would not be a problem for protein domains since the average protein domain size is around 100 amino-acids.

For reference, here is a paper where the authors compare different recombination systems, and another where the authors show a proof of principle experiment on how to use Gateway recombination to assemble functional proteins from cloned parts.