Protein purification by selective coacervation

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

Protein drugs are important in the treatment of diabetes, leukemia, hemophilia, Alzheimer's and Gaucher disease, and osteoporosis. They are also important therapeutic agents in organ replacement, tissue regeneration and wound repair, regardless of whether resulting from disease, aging or battle related injury. The technologies for large scale protein separation needed to produce these drugs have lagged behind molecular biology, and now are responsible for most of their cost. The use of generally recognized as safe (GRAS) polymers (polyelectrolytes) are investigated to isolate and concentrate the target proteins from the cell crush or lysate in which they are formed. The process by which this happens is a spontaneous separation into two liquids: the more dense phase contains the polymer and the target protein in high concentration. The goal of this work is to understand the principles by which this complex coacervation can be optimized by (a) the selection of the polymer, (b) the choice of the conditions for effecting the coacervation, and (c) the method of removing polymer from the target protein. The interdisciplinary coupling of bioengineering, bioanlytical, and polymer physical chemistry proposed provide an example of the unification of perspectives appropriate to progress in this field. The PIs take a pro-active role in involving members of underrepresented groups in research. Both gender and racial minorities make up a significant proportion of their groups. There are currently nine women in the two groups (1 postdoc, 4 graduates, 3 undergraduates, 1 high school senior), three of whom are involved in work related to this proposal (protein polyelectrolyte coacervation). There is active participation in an NSF REU and IGERT grants for promoting undergraduate research. Students working on this project will obtain training in areas of great importance to biotechnology and pharmaceutical innovation and applications.