Department of Chemistry
Proteins are a major class of biomolecules that often lie at the heart of human disease. G-protein coupled receptors (GPCRs) are one of the largest classes of proteins identified in the human genome to date. They are present almost ubiquitously in all cell and tissue types and are key players in the signaling processes that enable cells to carry out their proper functions. Their central role in cell signaling makes them desirable targets for the pharmaceutical industry. Up to 50% of drugs in development are aimed at targeting this particular family of receptors. Their role in cellular signaling is complex and filled with intricacies that remain poorly understood. Further complicating our understanding of this process is that recently it has been reported these receptors associate very closely with one another. For example, the adenosine A2a receptor, a GPCR, plays an integral role in the body’s inflammatory response which can lead to the development of heart disease. Both in vivo and in vitro studies reportedly show this receptor self-associates to form a complex called a “dimer." The physiological effect of this phenomenon remains unclear, although, it has been suggested to serve as a means of regulating receptor activity at the cell surface. One of the aims of our work is to understand how the lipid bilayer influences GPCR association, specifically.
GPCRs are just one family of proteins that belong to a special class called "membrane proteins." These elusive proteins have presented significant challenges to researchers for years in part because of their unique physiochemical properties which render them difficult to produce and isolate in a physiologically active form outside of the environment of the cell. When this is accomplished traditional biochemical and biophysical experimental techniques must often be adapted in such a way that these proteins can be studied in a native-like environment outside the cell. This often includes the use of detergents and lipids. In many cases the difficulty lies in producing sufficient quantities of these proteins for structural characterization and other downstream studies. We are also interested in exploring and optimizing the methodology used to produce membrane proteins for these types of studies and believe this work will help open up the "bottleneck" that has slowed progress in the field and hampered our understanding.