SBIR Phase II: Development of a Eukaryotic Membrane Protein Overexpression System

This Small Business Innovation Research (SBIR) Phase II project concentrates on creating a novel, economical and powerful production technology for eukaryotic membrane proteins, a group of proteins that remain intractable yet are of tremendous medical and scientific importance. A majority of membrane proteins are very difficult to obtain in any significant quantities, even at milligrams scale since their natural biosynthesis levels often are very low and currently available production methods are not effective for membrane proteins. This research project will utilize a versatile and easy-to-cultivate microorganism that can generate proliferated membranes under certain conditions to host the recombinant membrane proteins. The efficiency of various strategies will be evaluated through activity assays and direct protein isolation. The broader impact of the technology are new generations of efficacious medicines in virtually all therapeutic areas including infectious diseases, cancer, genetic diseases due to genetic defect in membrane proteins, central nervous system diseases, cardiovascular system diseases, digestive system diseases and many others. The impact of this technology in science, in medicine and in society will be very significant. The technology can be utilized to mass-produce a very large number of membrane proteins, especially surface membrane proteins for applications in structure-based drug design, in protein engineering, in protein therapeutics, and for the development of diagnostics and vaccines against infectious diseases and cancer. These efforts will not only provide new scientific understandings of very difficult-to-study membrane proteins but also eventually transform the current landscape of diagnostics and therapeutics for human diseases and illnesses.