Miss Fan Ying

Biography

I am currently a PhD student in the School of Chemical and Biological Engineering as well as Clinical Dentistry, working for Professor Phillip C. Wright and Dr. Graham Stafford. I obtained my Bachelor Degree in Biomedical Engineering from Tianjin Medical University in China in 2011, completed Master Degree in Biotechnology from the University of Glasgow in UK in 2012. My PhD project is by using synthetic biology tools to make E. coli to produce mammalian collagen, which eventually can be widely used in medical transplantation for patients.

Supervisor: Professor Phillip C Wright

Biological and Environmental Sytems

Publications

A newly identified TSHb splice variant is involved in the pathology of Hashimoto’s thyroiditis ' (Journal of Endocrinology)

Research

Collagen is a group of nature proteins found in multicellular animals’ tissues. Type I collagen consists of two α1 chains and one α2 chain that are coiled, normally in a repeating Gly-X-Y triple-helical formation. During the co- and post-translational modifications, peptidylproline cis-trans isomerase (PPI) activity, prolyl-3-hydroxylase (P3H), prolyl-4-hydroxylase (P4H) and lysyl hydroxylase are necessary to selectively convert residues in the Y position of propeptide into hydroxyproline and hydroxylysine. By following glycosylation reaction to hydroxylysine, those three left-handed helices are twisted together into a right-handed coiled-coil (triple helix) structure. As collagen fibers are a promising candidate in both clinical and industrial applications, many investigations have been made in large-scale production of recombinant expression of collagens and fragments of collagens, particularly human type I collagen.

Bacteria flagellum is a lash-like appendage that protrudes from the bacterial cell body. It is not only a highly efficient nanomotor for cells swim, but also with additional functions in injection of toxic protein into host cells, as a virulence secretion system, either to invade or to kill. In E. coli flagellum, the flagellar hook and filament structure are mainly followed by the hook (FlgE), the hook-filament junction (FlgK, FlgL), and eventually by the filament (FliC), and the filament cap (FliD). The E. coli flagellar type III export apparatus associated with the motor, takes significantly function in exporting flagellar hook and other filament components via the cell envelope. Therefore, such E. coli flagellar type III protein export apparatus becomes an efficient protein export apparatus of human type I collagen. It is also a candidate as a secretion system for biomanufacturing proteins employing a prokaryotic host.
Currently, I am working at reconstructed human collagen 1A1 plasmids. Whole human collagen 1A1 fragment is divided into five smaller parts, and each function is explored by protein secretion test in a ready constructed strain, which truncated flagellar structure has been demonstrated by proteins secretion, via targeting with an mRNA and protein signal to the E. coli flagellar type III secretion apparatus. Meanwhile, for the purpose of improving stability of collagen triple helices, additional domains are constructed into the plasmids with particularly small fragments of human collagen IA1, and further explore their functions in the same strains. My colleagues are working at the E. coli metabolic network for the purpose of solving issues that prokaryotic systems are lack of post-translational modification of proline residues, which so that improve the production of proline rich human collagen.