Muscarinic acetylcholine receptors are drug targets for Alzheimer’s disease, schizophrenia, and Parkinson’s, but their five subtypes are nearly identical where drugs normally bind, making selective medicines hard to design. This seminar shows how drugs can instead target a second, less-conserved site to achieve selectivity. Using molecular pharmacology and cryo-electron microscopy, we determined how subtype-selective positive allosteric modulators distinguish one receptor subtype from another. Together, these findings provide a structural blueprint for designing safer, subtype-selective muscarinic drugs.

About the speaker: Dr David Thal is an Associate Professor at the Monash Institute of Pharmaceutical Sciences, where he leads the Analytical and Structural Neuropharmacology Laboratory. His research uses biophysical techniques, molecular pharmacology, and chemical biology to understand how ligands engage therapeutically relevant proteins, with a particular focus on protein allostery and G protein-coupled receptors. This work has produced high-impact publications in journals including Nature, Cell, PNAS, and Nature Chemical Biology, and has contributed to international efforts to classify muscarinic acetylcholine receptors through the IUPHAR nomenclature subcommittee. His research is supported by an NHMRC Investigator Leadership Grant. David serves as DDB HDR Coordinator and as Treasurer of the Melbourne Protein Group.

Join us: ACMD Auditorium

Level 1, 27 Victoria Parade, Fitzroy

(enter via Nicholson Street)