Mechanisms and Engineering to Control Aggregation of Therapeutic Proteins
Speaker: Christopher Roberts, University of Delaware
Department: Chemical & Biological Engineering
Location: Engineering Quadrangle A224
Date/Time: Wednesday, March 6, 2013, 4:00 p.m. - 5:00 p.m.
Protein aggregation is a perennial issue during biopharmaceutical product formulation and process development. Aggregation of native or folded proteins is also a long-standing area of research for bio-separations, and because of its implications for limiting drug dosage or delivery options. Protein engineering is a promising approach for rational design of molecules that are resistive to aggregation, and so are better candidates for product development. However, it is important to couple engineering approaches with mechanistic insight as to how best to balance the different factors that control aggregation of different proteins. This seminar focuses on experimental, modeling, and protein-engineering approaches to mechanistically control and predict how protein folding and protein-protein interactions affect aggregation and self-assembly of therapeutic and model proteins. In addition, we have developed a novel approach to quantify protein interactions and thermodynamics at high concentrations, combining laser scattering with statistical thermodynamics based on the seminal work of Kirkwood and Buff. Our model systems include a range of different proteins; from pharmaceutical antibodies, to insulin, eye-lens crystallins, and enzymes.