Phase I of the program will focus on obtaining RNA-like molecules that are sufficiently robust polymerases (ribozyme polymerases) that they are able to copy their own sequence. The Phase I program will exploit a combination of molecular design and laboratory selection to generate structures that undergo self-reproduction with heritable mutation.
Phase II will be devoted to evolving ribozyme polymerases into ribozymes that are capable of robust self-replication (replicases) and the integration of a replicase into a complete replicating cellular system. Additional goals will focus on the laboratory evolution of new catalysts, artificial pathways, artificial regulatory systems, and emergent behaviors that are found in living systems, exploiting the ribozyme polymerases developed in Phase I.
The increased resources made available to the Phase II Center will allow expansion of the number of laboratories that participate in development of Darwinian synthetic biology. Crystallographers and NMR spectroscopists will be involved to develop the structural biology of the ribozyme polymerase and other catalysts that emerge from the proposed research. Systems biologists will bring their expertise in quantitative mathematical modeling to the dynamic systems that emerge. The contributions of chemical and mechanical engineers will be useful for automating some of the selection procedures as they become more standardized. Additional synthetic chemists, physical organic chemists, inorganic chemists, and materials scientists will be recruited to prepare molecules, quantitatively assess mechanisms, understand the roles of metal cofactors, and develop potential technology outlets, respectively.