Special Seminar - Improving Nature’s Design: Engineering Peptides and Proteins for Enhanced Fitness and Function
Date: March 13, 2012
Time: 12:00 PM
Location: Bossone Research Enterprise Center, Room: 709
Amy J. Karlsson, PhD
School of Chemical and Biomolecular Engineering
The fitness and function of proteins and peptides can be engineered using either rational design or directed evolution approaches. Rational design uses information about a protein or peptide’s structure and function to make informed decisions on the amino acids to target for mutation, while directed evolution involves making random changes in sequence and then screening for a desired property. In this seminar, I will describe my work in rational design and directed evolution to engineer proteins and peptides with biological applications. My PhD research utilized rational design to engineer non-natural antimicrobial β-peptides that exhibit antifungal activity against the human pathogen Candida albicans. Through this work, we developed a deeper understanding of the properties of β-peptides that contribute to their toxicity towards fungal cells and fungal biofilms. My postdoctoral research employs directed evolution to engineer antibodies that fold and function inside cells, where the reducing environment prevents formation of the disulfide bonds normally required for proper antibody folding. We have developed a bacterial inner membrane display system that harnesses the cytoplasmic folding quality control mechanisms of the Escherichia coli twin-arginine translocation pathway to display only proteins that are well folded. We used this method to display a combinatorial library of single-chain variable fragment antibodies (scFvs) and screened for binding to a target protein antigen. Our approach isolated scFvs with dramatic improvements in both antigen-binding and intracellular solubility. Together, rational design and directed evolution create a powerful set of tools for engineering proteins and peptides to have the improved fitness characteristics and biological activity required for a broad range of applications.
Dr. Amy Karlsson received her bachelor’s degree in chemical engineering from Iowa State University in 2003 and then joined Prof. Sean Palecek’s group at the University of Wisconsin, where she received her PhD in chemical engineering in 2009. Following her doctoral work, she started her current postdoctoral position with Prof.Matthew DeLisa’s lab in Chemical and Biomolecular Engineering at Cornell University. Dr. Karlsson is the recipient of an NIH Ruth L. Kirschstein Postdoctoral Fellowship from the National Cancer Institute.
The Bossone Research Enterprise Center is located at the corner of 32nd and Market Streets.