Fabrication of Modular Human Collagen and Collagen Variants in Yeast
Speaker: Polly Chan, Ph.D.
Collagen, the most abundant extracellular matrix (ECM) protein, has been widely used in tissue scaffold and drug delivery applications. Synthetic genes that express variants analogous to native full-length collagen have not been previously synthesized, and synthetic chemical compounds or short collagen fragments have been used as biomimetic models instead. These conventional materials, however, exhibit properties that can be non-representative of native collagen. Synthesizing a full-length recombinant collagen gene to produce a closer analog of collagen is challenging due to the repetitive nature and length of the collagen genes. By recoding the human collagen III gene using degenerate codons, our research group successfully synthesized the first full-length synthetic human collagen gene and several specifically-defined variants. Concurrently, we have developed a novel modular “bottom-up” collagen gene assembly platform that allows fabricating collagen-based protein biopolymers by mixing-and-matching domains containing native or foreign cell interaction signals or tissue matrix functional groups at precisely-defined locations. This provides tremendous flexibility in generating biomimetic protein mutants with independent biological and material properties. Our modular collagen platform opens doors to creating a new class of biopolymers that can be engineered to direct cellular activities, to exhibit novel matrix physicochemical properties, and at the same time to retain desired native ECM protein properties.
Dr. Polly Chan is a recent graduate of the Chemical and Biochemical Engineering PhD program at UCI. Prior to UCI, she obtained a BS degree from the University of Southern California and a MS degree from the Queen’s University, Ontario, Canada. She was co-supervised by Prof. Szu-Wen Wang and Prof. Nancy Da Silva and her PhD research was focused on recombinant protein and yeast engineering. Currently, she is working as an Assistant Specialist in our department to continue her research on the collagen project.