This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
0853801 Shusta
Intellectual merit
Protein therapeutics (biopharmaceuticals) are increasingly being used for the treatment of a variety of diseases. Over 165 biopharmaceuticals are currently on the market and hundreds more are in development, representing more than one-third of the current pharmaceutical pipeline. One of the major hurdles in the development of any protein biopharmaceutical is the production of high quality recombinant protein at a level that can meet demand in an economically feasible manner. Unfortunately, present methods for optimization of protein secretion strains have not yielded significant improvements despite substantial effort and innovation. In this project, a novel approach for yeast strain engineering that takes advantage of the transcriptional control of the unfolded protein response (UPR) is presented.
Broader impacts
This project provides a new conceptual framework and toolkit for the optimization of protein production strains. Reverse engineering in the form of microarray analysis also has the potential to initiate new directions of research based on the molecules and pathways that had been previously unassociated with improved protein processing within the cell. Next, the project is designed to train a graduate student and several undergraduate students in the cross-disciplinary fields of bioprocessing and protein engineering to prepare them for careers in industry and academia. The PI has trained 31 undergraduate and graduate students, several of whom are from underrepresented backgrounds. Research results will be integrated into courses that the PI regularly teaches as protein engineering modules in his "Design of Biological Molecules" graduate course and as coupled transport-reaction problems in his undergraduate mass transfer course. Finally, research results will also be disseminated to high school students in the form of the Wisconsin High School State Science Olympiad, through an "Applied Protein Modeling for Medical Uses" symposium that the PI organizes and hosts.
