Membrane proteins, which make up approximately one-third of all proteins in a cell, are responsible for a variety of processes, making them attractive therapeutic targets for many diseases such as hypertension, diabetes, neurological disorders and cancer. Understanding membrane protein function depends on studies of physical interactions of these proteins within protein complexes. However, investigation of membrane protein interactions in cells is difficult due to their complex chemical features. This represents a major obstacle in attempts to investigate the biology of deregulation of integral membrane proteins leading to human diseases, and consequently hinders the development of improved, targeted therapies. Hence, there is a significant need in the biomedical community for a fast, reliable and unbiased assay to study membrane protein interactions in their native membrane environment. Recently Dr. Stagljar’s lab developed a powerful new technology for use in the study of membrane proteins called the Mammalian Membrane Two-Hybrid (MaMTH). This technology represents a significant scientific advance, allowing the large-scale study of membrane protein functional interactions directly in the context of the living cell, and in response to changing environmental conditions and mutation, and thus has high commercialization potential. In this proposal the team seeks to expand the MaMTH technology, transforming it into a cutting-edge commercial platform for biopharmaceutical research to allow for the study of membrane protein function, and membrane protein association with disease, on a so far unprecedented scale.