Our group is leading an effort to adopt and refine powerful strategies from synthetic biology to create a systematic approach for glycocalyx engineering. We design and genetically encode new biopolymers with the specific intent to manipulate the chemical and physical structure of the glycocalyx. Leveraging the speed and low cost of modern DNA fabrication platforms, we can build DNA instruction sets for desired biopolymers in as little as 1-2 weeks, enabling new material states of the glycocalyx to be rapidly programmed into cells and tested. We are continuing to devise genetic blueprints that direct assembly of increasingly more complex material states on the cell surface, both as an approach for basic research and as a commercially relevant biotechnology.
Shurer CR, Colville MJ, Gupta VK, Head SE, Kai F, Lakins JN, and Paszek MJ. 2018. Genetically Encoded Toolbox for Glycocalyx Engineering: Tunable Control of Cell Adhesion, Survival, and Cancer Cell Behaviors. ACS Biomater. Sci. Eng. 4(2): 388-99.
Shurer CR, Head SE, Goudge MC, Paszek MJ. 2019. Mucin-coating technologies for protection and reduced aggregation of cellular production systems. Biotechnol Bioeng. 116(5):994-1005.
Shurer CR, Wang Y, Feeney E, Head SE, Zhang VX, Su J, Cheng Z, Stark MA, Bonassar LJ, Reesink HL, Paszek MJ. 2019. Stable recombinant production of codon-scrambled lubricin and mucin in human cells. Biotechnol Bioeng. 116(6):1292-1303.
Pan H, Colville MJ, Supekar NT, Azadi P, Paszek MJ. 2019. Sequence-specific mucins for glycocalyx engineering. ACS Synth. Biol. 8(10): 2315-26.
Shurer CR, Kuo JC, Roberts LM, Gandhi JG, Colville MJ, Enoki TA, Pan H, Su J, Noble JM, Hollander MJ, O’Donnell JP, Yin R, Pedram K, Möckl L, Kourkoutis LF, Moerner WE, Bertozzi CR, Feigenson GW, Reesink HL, and Paszek MJ. 2019. Physical Principles of Membrane Shape Regulation by the Glycocalyx. Cell 177(7):1757-70.
We are leaders in engineering the material state of the glycocalyx
The field of synthetic biology has formalized an approach to biological design based on fabrication and assembly of engineered biological parts. Our vision has been to adopt the powerful approaches of synthetic biology to design and fabricate new material states of the glycocalyx.
Mucins offer many advantages as a building block for cell-surface materials. Their length, backbone chemistry, and distribution of potential glycosylation sites are precisely encoded in DNA. We can easily design and encode polymer backbones that are longer or shorter, more charged or less charged, and with more or less sites for addition of glycan side chains.