SBIR-STTR Award

Current manufacturing platforms are adequate for large-scale expression of a wide range of genetically engineered proteins, which are of interest to the DOE’s Genomes-to-Life program. Nevertheless, these systems often fall short of the production targets of many membrane and secreted proteins. Such proteins are indispensable to cell survival and are among the most important products under development by the biopharmaceutical industry. This project will develop a novel platform technology for the production of membrane and secreted proteins based on the common pond-water ciliate, Tetrahymena thermophila. Phase I will test whether a model membrane protein can be over-expressed in this system, in a form that can be rapidly purified at low cost. A positive result will set the stage for Phase II, where the technology will be used for high-throughput expression and purification of large numbers of proteins from different species.

Commercial Applications and Other Benefits as described by the awardee:
The technology would be made available to individual investigators and the biopharmaceutical industry through contract protein expression services and user-friendly kits, which would have direct application to vaccine development, therapeutic protein manufacture, rational drug design, and industrial processes that include alternative energy production

Genetically engineered proteins are now being used in a wide range of critically important applications, including bioremediation, alternative energy production, and the treatment and prevention of human and animal disease. However, current manufacturing platforms are limited to a small number of cell-based systems that rely on bacteria, fungi, and insect and mammalian tissue culture cells. While adequate for the production of soluble proteins, these platforms often fall short of the large-scale manufacturing processes that are needed to produce the membrane and secretory proteins that are now under scrutiny by the energy and pharmaceutical industries. This project will develop a novel platform technology ¿ based on a common pond-water ciliate, Tetrahymena thermophila ¿ that is ideally suited to the rapid, low-cost production of such difficult-to-express proteins. Phase I demonstrated the utility of this approach for overproduction and rapid purification of a flu vaccine antigen, which served as a model membrane/secretory protein. Phase II will apply this technology to the production of enzymes being developed for biofuel manufacture. In addition, Tetrahymena¿s vast membrane system will be exploited to overproduce a G-protein-coupled receptor; then, it will be demonstrated that the receptor can be labeled with stable isotopes for structure-based studies with NMR.

Commercial Applications and Other Benefits as described by the awardee:
The new platform technology should have direct application to vaccine development, therapeutic protein manufacture, rational drug design, and industrial processes, including alternative energy production. The technology would be made available to government, industry, and academia through contract protein expression services and user-friendly kits