Grant: Operating Grant

The G-protein coupled receptors form the largest family of cell surface proteins with over 1,000 members. They are involved in the recognition and response to stimuli as diverse as hormones, neurotransmitters, calcium, odorants, gustatory signals or light. Their key roles in cells have made them the target of more than 60% of all currently prescribed drugs, including drugs to treat heart failure, chronic pain, obesity, neuropsychiatric disorders and carcinomas. Although the symptoms of these diseases are well understood, the molecular mechanisms that underlie them are not. The overall objective of our project is to identify and characterize the role of proteins associated with one hundred selected human G-protein coupled receptors as well as to understand how these proteins, when impaired, contribute to the development and progression of various human diseases. To that end, we are using a state-of-the-art technology developed in my laboratory that is able to detect interactions involving proteins on the cell surface. In addition, we will investigate the cellular mechanisms in which these proteins are involved using computational approaches as well as traditional techniques, including biochemical, cell biological and molecular biological assays. We hope to provide a more complete understanding of the role of these proteins in the normal operation of human cells, and to gain insight into the cellular mechanisms involved in human diseases that result from the malfunction of these proteins. This understanding should provide potential avenues for additional therapeutic interventions against heart failure, chronic pain, obesity, neuropsychiatric disorders and carcinomas.