C-GEM seeks to establish a fundamentally new way to program chemical matter and transform the way we produce materials and medicines. The science is spectacular—a wholesale re-engineering of the natural translation machine to produce genetically encoded chemical polymers with precisely defined sequences and unprecedented functions. To catalyze these efforts, C-GEM will implement GEM-NET, a sophisticated data management system to promote data sharing within and outside the team, and with industry, the NSF, and the public. By fostering innovation at the chemical-biology-materials frontier, C-GEM will establish a diverse chemical workforce, integrate research with training, and captivate scientists and non-scientists alike.
C-GEM seeks to solve a “Holy Grail” level problem in modern science: the inability to prepare polymers whose monomers are defined with protein-like control. Sequence-defined polymers possess extraordinary potential for information storage, anti-counterfeiting, drug delivery, remediation, even drug discovery, and much more, but strategies to prepare them are barely in their infancy.
C-GEM will synthesize sequence-defined chemical polymers by repurposing the E. coli translational apparatus to promote bond-forming reactions between monomers that are not α-amino acids, but instead the building blocks for aramids, polyolefins, polyurethanes, even polyketide precursors.
This goal demands orthogonal enzymes that acylate orthogonal tRNAs with each monomer, efficiently and in vivo; orthogonal ribosomes that accept these tRNAs as substrates and elongate the products; genomically recoded organisms with multiple open codons to enable mRNA-templated synthesis of sequence-defined polymers; and high-resolution structural data to deepen understanding and inform design.
Phase I efforts will develop the multi-disciplinary tools and technologies to accomplish this goal. In
Phase II, an expanded team of chemists, biologists, engineers, computational and materials scientists, and industrial partners will expand these efforts to biosynthesize, characterize, and interrogate multiple classes of truly exotic chemical polymers, containing 3 or more distinct monomers per class—products that can only be generated in recoded organisms whose ribosomes support novel chemistries.
Sequence-defined chemical polymers are the materials of tomorrow.
EteRNA is a ‘citizen science’ video game created by C-GEM member Rhiju Das that engages users to solve puzzles related to the folding of RNA molecules. Rhiju has built EteRNA into a massive open laboratory to design molecular medicines, get feedback from real experiments at Stanford’s School of Medicine, and turn findings into scientific publications.