Thanks to a $1.8 million grant from the National Science Foundation, an interdisciplinary team of Yale researchers will soon make headway on the next frontier of synthetic biology — re-engineering cells to produce novel synthetic polymers.
The NSF grant establishes the Center for Genomically Encoded Materials, or C-GEM, headed by chemistry and molecular, cellular and developmental biology professor Alanna Schepartz. C-GEM was one of only five Phase I NSF Center for Chemical Innovation grants awarded this year, and it is the first CCI grant awarded to Yale. Other principal investigators include molecular biophysics and biochemistry and chemistry professor Dieter Söll, MCDB professor Farren Isaacs, biostatistics and ecology and evolutionary biology professor Jeffrey Townsend, as well as chemistry, biophysics and structural biology professor Jamie Cate from the University of California, Berkeley.
C-GEM will explore how to create new chemical polymers of a prescribed sequence and length by modifying ribosomes — the cell’s main protein synthesis machinery — inside E. coli cells. Ribosomes typically promote bond formation between natural amino acids known as alpha amino acids. However, C-GEM plans to re-engineer these ribosomes to also incorporate beta amino acids and other molecules — which are not naturally encoded — into sequence-defined oligomers. These polymers could possess fundamentally different properties than materials that exist today, Schepartz said.
“This project’s goal is to repurpose ribosomes, to use this splendid, beautifully evolved and efficient machinery to make new biomaterials,” Söll said. “I think the center will provide something to Yale that we do not have at the moment — a place and a program that brings people with different expertise together and allows them to work on such an outside-of-the-box problem.”
Using the ribosome to make unnatural proteins is not a new concept, Schepartz noted, adding that several groups have done pioneering work in this field over the last two decades. Only recently, however, have researchers discovered that it is possible to customize the sequence of monomers by modifying the active site that ribosomes use to link different amino acids together.
Armed with this new knowledge and recent advances in genome technologies, C-GEM can now investigate how specifying the exact sequence of monomers in a protein could lead to the construction of more thermally stable and degradation-resistant materials, among other possibilities, Schepartz said.
“We can guess at some of the features that will be present in these materials, but at some level we don’t know, because we’re simply exploring a completely new quadrant of chemical sequence space,” Schepartz said. “That’s one of the most exciting things — if we are the group that makes these materials first, we are the ones who get to discover what properties ensue when you can define the sequence of a chemical polymer.”
Isaacs described the applications of these new polymers as “endless,” pointing to potential uses in creating water- and flame-resistant fabrics, improved military equipment, new classes of therapeutics and novel techniques in tissue engineering. Having precise control over the selection and placement of specific monomers is immensely powerful, Isaacs said, paving the way to “produce anything we can design.”
Although the grant officially started on Sept. 1, the collaboration began long before that date. In the past, the C-GEM team members all approached the challenge of engineering ribosomes to create new polymers from different angles, Schepartz said. But over the last few years, members of the team have started bringing together their varied expertise to tackle the problem, with the NSF grant now formalizing these efforts with funding.
“The current state of the field is a little bit dispersed in that we have individual researchers making progress on each of these pieces,” Townsend said. “[The center] enables those people to work together to generate new materials and actually change the way we live.”
One priority for this new collaboration will be to train future research scientists in an interdisciplinary manner, Schepartz said. Postdocs, graduate students and undergraduates will all be involved in the brainstorming process for new projects, and graduate students will be co-advised by faculty from both Yale and Cal, in addition to spending time working at both institutions.
In addition, the NSF grant supports the creation of a new online platform and data management system. This platform, which is known as GEM-Net and will be launched in November, will allow for more efficient exchange of information between C-GEM researchers, as well as make the center’s ongoing projects accessible to the general public, Townsend said. He added that as the center grows, the team will continue its outreach efforts by engaging the public with a series of podcasts and other interactive products.
“Piecing together combinations of exotic monomers will allow us to produce materials and therapeutics we can’t even think about today,” Isaacs said. “I’m convinced they’re going to be incredibly important in advancing our knowledge of these systems and having a big impact on society.”
Contact Ellen Kan at email@example.com .
Correction, Sept. 22: This story incorrectly ran under the headline “New center to advance biology research” when in fact the Center for Genomically Encoded Materials is formally funded under the chemistry division of the National Science Foundation and should be primarily regarded as a chemistry project.