Group Proposal: Rational Protein Bioprocessing with Hydrophobic Separations

Carnegie Mellon University, Pittsburgh PA

Investigators

Abstract

The objective of this project is the development of a quantitative tool that can be used to predict chromatographic performance as a function of adsorbed protein structure for given protein mixture/media/mobile phase combinations and to select/design hydrophobic media and mobile phase conditions. This tool will promote the process-scale use of hydrophobic media, resulting in simpler, more robust processes that reduce cost-of-goods and time-to-market for new and off-patent protein drugs. This project will advance the state of the art of hydrophobic chromatographic systems by addressing the following specific aims: (1) validate generic mechanisms for protein unfolding on adsorption to hydrophobic chromatographic media, (2) correlate linear and nonlinear protein-media interaction behavior using quantitative structure retention relationships (QSRRs) to connect protein retention to descriptors of native protein, perturbed protein, surface and solution physical properties, (3) develop a fundamental theory for protein-media interactions using a Langevin dipole approach to calculate protein-surface preferential interaction coefficients (PICs), and (4) predict chromatographic performance for complex mixtures by coupling QSRR correlations and/or PIC theory for protein-media interactions with a macroscopic/engineering description of chromatographic operation. This project is a collaborative effort among researchers at Carnegie Mellon University, Rensselaer Polytechnic Institute and the University of Virginia with expertise in biochemical engineering, applied biophysics, chromatographic separations, and thermodynamic modeling and computational chemistry. This collaboration, with the proposed regular program of team colloquia, laboratory rotations and industrial internships, is expected to provide a rich research and educational environment for the students and faculty alike.