Seminar:Dr. Erinç Şahin, June 03, Thursday, FENS L062, 10:30 A.M.

 Two case studies on the application of polymer physics and colloids science principles to protein aggregation                                 
                                 Dr. Erinç Şahin (University of Delaware)
Abstract:

a)    Gamma-D-crystallin: Engineering an extremely stable human eye lens protein for higher stability
b)    Four near-identical IgG1 monoclonal antibodies and outcomes of minor differences in stability
Protein aggregation can be defined as undesirable self-assembly of proteins. This phenomenon may lead to diseases (e.g. Alzheimer’s, Huntington’s, cataracts), decreased shelf life (e.g. vaccines, cancer targeting antibodies) and in extreme cases immunogenicity/toxicity (i.e. insulin) of biopharmaceuticals. Even in cases where formation of aggregates is not tied to any proven undesirable outcomes, it remains to be considered a major safety concern by the FDA; dictating the necessity of their elimination from final products. In our studies, we try to understand mechanisms of aggregation and develop methods to eliminate/slow/reverse their formation in an effort to improve manufacturing and formulation of biopharmaceuticals as well as to predict and increase shelf life of final products. Our approach to this scientific and industrial challenge involves utilization of various biophysical characterization methods in conjunction with the application of colloids science and polymer physics principles to protein self-assembly with computational help using mathematical modeling of multi-step chemical equilibria.
Sahin, E., Grillo, A., Perkins, M., Roberts, C.J. “Comparative Effects of pH and Ionic Strength on Protein-Protein Interactions, Unfolding, and Aggregation for IgG1 Antibodies”, Journal of Pharmaceutical Sciences, Early view: http://www3.interscience.wiley.com/journal/123447492/abstract
Sahin, E. et al.  “Computational Design and Biophysical Characterization of Aggregation-Resistant Point Mutations for g-D Crystallin Illustrate a Balance of Conformational Stability and Intrinsic Aggregation Propensity” (submitted to Biochemistry)

 June 03 2010, Thursday, FENS L062, 10:30-12:00 A.M.