Investigating the structural and molecular determinants of G protein-coupled receptor signaling bias.

We intend to find out how the most effective, target for drugs can be used in a greater number of ways than thought previously and with fewer side-effects. Our work involves the generation of a greater understanding of how G protein-coupled receptors (GPCRs: the target through which nearly half of all the current drugs in the world work) can control disease in up to three more different ways. These different forms of signaling are often called 'Biased Signals' as the specific drug effects can be channeled into one direction versus another. Our work intends to find out how many ways a drug effect can be biased at these super-important receptors that account for actually 1 in every 100 proteins in the body. It is interesting to note that for nearly all of the world's drugs currently targeting GPCRs were designed with the knowledge of only one of the three potential mechanisms that exist – indeed there may be even more than three different mechanisms! Our work can also pave the way for the discovery of these as of yet unknown mechanisms. In our proposal we focus on a therapeutic GPCR system that we have studied for over 10 years. We are going to investigate how we can identify mechanisms by which we can fine-tune a GPCR called the Relaxin-3 receptor to repair damaged DNA. DNA damage accelerates aging and the onset of nearly all major diseases, e.g. diabetes, cardiovascular disease and dementia. Put simply we will use biased signaling to design better drugs!

Keywords:BIOINFORMATICS, STRUCTURAL BIOLOGY

Disciplines:Bioinformatics data integration and network biology, Cell signalling, Structural biology

Project type:Collaboration project