Translational relevance of GPCRs involved in inflammation
Acute inflammation protects the body from foreign invaders, and as such, the innate immune response is critical in maintaining good health. Resolution of this inflammation is an ongoing process, which, if dysregulated results in a number of diverse disease states, including cardiovascular, autoimmune and cancer. Multiple G protein-coupled receptors (GPCRs) have been implicated in this resolution, including formyl-peptide receptors (FPR1 & FPR2), the leukotrienes (BLT1 & BLT2), and various orphans. These receptors can be activated by numerous specialised pro-resolving mediators (SPMs), resulting in multiple signalling cascades.
Understanding how these SPMs activate these resolution GPCRs is imperative for the discovery of pro-resolution drug molecules.
This project will investigate a number of these receptors to further elucidate their signalling and function, including the possible identification of bias signalling, and their relevance in human cells.
To do this, key areas will be investigated:
1. Use of basic signalling assays to elucidate the pathways activated by these SPMs of resolution GPCRs.
2. Use of human neutrophils isolated from healthy blood donors to further explore receptor signalling and the role of these GPCRs and SPMs in native cells.