Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of rec ....Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of receptor, the project expects to provide significant benefits to the research field by impacting on future drug discovery efforts, not only at mAChRs, but at other structurally related receptors.Read moreRead less
Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GP ....Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GPCR function and signalling remain unanswered. The primary outcome of this project is to provide mechanistic insight into the dynamics of GPCR ligand recognition and activation to advance our understanding of GPCR signal transduction, a fundamental biological process for all living organisms.Read moreRead less