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Title: A Suite Of Tools For Reporting And Engineering Protein Folding, Interactions, And Post-Translational Modifications In The Bacterial Periplasm
Authors: Mansell, Thomas
Keywords: Protein Engineering
Issue Date: 31-Jan-2012
Abstract: Therapeutic protein drugs are part of an emerging new generation of pharmaceutical products. However, production of such drugs is expensive due to the complex nature of many human proteins and post-translational modifications required for physiological efficacy and pharmacokinetic activity. We have developed several tools to improve production of human-like proteins in a relatively inexpensive host, Escherichia coli. First, we developed a system for monitoring and engineering protein solubility in the bacterial periplasm, a compartment with many useful features for heterologous protein expression. Next, we developed a system for monitoring protein-protein interactions in vivo in the periplasm, which we can leverage for the production of novel and improved antibodies and antibody fragments. Building upon our protein folding reporter technology, we have developed a system for examining the effect of N-linked glycosylation, an important post-translational modification, on protein folding in vivo. This system allows us to (1) study the effect of glycosylation on folding of various glycoproteins from pathogenic organisms and (2) create a genetic selection with the purpose of engineering the glycosylation pathway using the versatile E. coli as a host. Finally, we have created a modified genome-scale flux balance analysis model of E. coli to determine in silico metabolic factors that affect glycosylation efficiency.
Committee Chair: Delisa, Matthew
Committee Co-Chair: Varner, Jeffrey D.
Committee Member: Shuler, Michael Louis
Discipline: Chemical Engineering
Degree Name: Ph.D. of Chemical Engineering
Degree Level: Doctor of Philosophy
Degree Grantor: Cornell University
No Access Until: 2017-06-01
Appears in Collections:Cornell Theses and Dissertations

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