Understanding trafficking and membrane localization to re-engineer host and GPCR protein for improved expression

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This NSF award by the Biotechnology, Biochemical and Biomass Engineering program supports work to develop improved expression systems for integral membrane proteins. Integral membrane proteins play critical roles in cell signaling, and are implicated in a wide range of human diseases such as asthma, obesity, cancer, heart disease, and chronic pain. Biophysical and biochemical studies of membrane proteins require large quantities of purified protein; even more than soluble proteins, because they need to be solubilized in detergent solutions. Results for many classes of membrane proteins suggest that in traditional expression systems, valuable targets of drug discovery and biochemical importance will be understudied because researchers cannot make sufficient protein. The goal of this research effort is to improve the expression of an important class of membrane proteins, the G protein-coupled receptor family (GPCRs). Specific aims are to identify cellular and molecular features of both the proteins and expression host to achieve the highest level of active GPCRs for structural and biophysical characterization. In addition, specific educational examples will be developed for the undergraduate Heat and Mass Transfer course. Graduate and undergraduate students will be trained in the laboratory, with particular efforts focused on representation from women and under-represented groups.