Novel approaches to discover new peptides for orphan G protein-coupled receptors - Dr Simon Foster, Cardiac Bioengineering Group at QIMR Berghofer Medical Research Institute.

Abstract:

G protein-coupled receptors (GPCRs) constitute the largest family of cell-surface receptors and are involved in nearly all aspects of biology, yet over 100 human GPCRs have not been definitively paired with endogenous ligands. These ‘orphan receptors’ represent a treasure-trove of unexplored biology and have strong potential to influence human physiology and disease processes.

As part of a large international collaboration, we sought to identify new peptide ligands from the human proteome that activate orphan GPCRs. Capitalising on the wealth of comparative genomics data and leveraging bioinformatic data on human GPCRs, we identified common features of peptide GPCRs and applied statistical and machine learning analyses to identify putative peptide ligands. We then used a multifaceted experimental approach to capture peptide-mediated orphan receptor signalling responses. After extensive validation, we discovered and characterised novel pairings of 17 peptides with five different orphan GPCRs, and identified potential new ligands for nine additional peptide GPCRs. We envisage that these findings will lay the platform for future studies on these peptides and receptors to fully illuminate their roles in human physiology and disease.

Biography:

Dr. Simon Foster is an emerging leader in molecular pharmacology and cardiovascular physiology whose research is focussed on the identification and understanding of novel aspects of G protein-coupled receptor (GPCR) biology. Simon has recent publications in leading journals including Cell, British Journal of Pharmacology, Journal of Biological Chemistry, PNAS and Molecular Pharmacology, and was awarded the ASCEPT/BPS Outstanding Young Investigator Prize and the Certara New Investigator Award in 2019. He received his BA/BSc (Hons) degrees from the University of Melbourne and then gained his PhD in 2014 from the University of Queensland for his studies on odorant and taste receptors in the heart. Having being awarded consecutive Postdoctoral Research fellowships from the Lundbeck Foundation and the Danish Council for Independent Research, Simon moved to the University of Copenhagen (Denmark) in 2015, where he began working on orphan GPCRs. He returned to Australia in 2018 to investigating new aspects of chemokine receptor signalling at Monash University, and has recently joined the Cardiac Bioengineering Group at QIMR Berghofer Medical Research Institute.