The Biological Rosetta Stone algorithm is a Synthetic Biology approach to research that involves developing increasingly complex libraries of scaffolded molecular structures that are complemented with nested biophysical models to develop a self-consistent and hierarchical understanding of our synthetic constructs.
We do this by first taking characterized genomic parts and putting them together or “wiring” them in novel architectures (depicted by the sequence in the top panel), next we develop a structure based thermodynamics model (middle panel), and finally we analyze the regulatory output using our model to try to extract the underlying design principles that will enable us to translate the structural architecture and sequence to some computational algorithm (bottom panel).
The litmus test is simple: if we can write a sequence down whose output can be predicted from the computational rules depicted in the Rosetta Stone, we can then apply this “key” to natural regulatory sequences in an attempt to decipher the regulatory genomic code.
To bring this approach to fruition, we need to complement our constructionist skills with advanced single molecule imaging and microscopy techniques, as well as relying on statistical thermodynamic modeling. So far we have managed to take step 1: we had shown that this approach can indeed lead to a new understanding of many natural examples in bacteria.