Workshop 8: Crash-course on quantification of Allostery and Biased Signalling at G protein-coupled receptors
Tracks
Track 2
| Tuesday, December 9, 2025 |
| 1:30 PM - 3:30 PM |
Details
Introduction. Major life science challenges include, understanding how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. After centuries of relentlessly exploring how receptors are regulated by endogenous and/or drug-like molecules, new ideas have emerged in the field that have completely changed and revitalized it. The first paradigm is biased signalling, which is the ability of structurally distinct ligands to stabilise different pools of receptor conformations leading the distinct cellular outcomes. The second paradigm is allostery, which is the mechanism by which some ligands (synthetic or natural) can recognise and bind different regions of receptors compare to the endogenous hormone (orthosteric) binding site, and consequently alter the physiological responses. However, both allostery and bias are very complex, making reproducibility and description challenging.
Methods. This workshop will use key novel analytical models to analyse and interpret allostery and bias signalling at a major family of GPCR, the muscarinic acetylcholine receptors.
Results. Here, we provide definitions, guidelines and analytical models for any scientists to quantify and report allostery and ligand bias, using data generated in our laboratory.
Discussion. The workshop will also allow any participant to join with their own set of data, exploring either allostery or bias, and the team will assist with data analysis, representation and interpretation.
Speaker
Dr Vi Pham
Monash Institute of Pharmaceutical Science
Co-chair and facilitator
Biography
Vi Pham obtained her PhD from the Howard Florey Institute at University of Melbourne under the supervision of Professor Patrick Sexton. In 2018, she joined the Analytical and Structure Neuropharmacology laboratory at the Monash Institute of Pharmaceutical Sciences (MIPS, Monash University) as a postdoctoral research fellow. Her research focuses on elucidating the mechanisms of drug action at G protein-coupled receptors (GPCRs), with a particular interest in biased agonism and allosteric modulation. Currently she is investigating novel small molecules that selectively target muscarinic acetylcholine receptors and opioid receptors with the aim of developing new therapeutic strategies for neuropsychiatric disorders and chronic pain.
Dr Alastair Keen
Research Fellow
Monash Institute of Pharmaceutical Sciences
Co-chair and facilitator
Biography
Dr. Keen is a postdoctoral researcher within the Spatial Organisation of Signalling Laboratory. Dr. Keen obtained a dual PhD from Monash University and The University of Nottingham, UK, in Molecular Pharmacology and Drug Discovery. Prior to this he completed a Master of Biotechnology at The University of Melbourne.
His current research in the Spatial Organisation of Signalling Laboratory employs techniques such as proximity-dependent labelling proteomics, confocal microscopy and bioluminescence resonance energy transfer to investigate GPCR regulatory mechanisms and compartmentalised signalling processes.
His work has been published in high quality journals including Nature, eLife, and Br. J. Pharmacol. Dr. Keen is currently supervising two PhD students. He has also successfully supervised two honours students, with Ms. Shaqayeq Ramazani having received the Fred Mitchelson Award in 2024 for the highest mark in the cohort. Dr. Keen serves on two PhD panels, chairing one. He also leads the MIPS-Drug Discovery Biology Level 3 laboratory committee.
Dr Shane Hellyer
Monash Institute of Pharmaceutical Sciences
Assistant
Biography
Dr Hellyer is Deputy Head of the Endocrine and Neuropharmacology Lab at the Monash Institute of Pharmaceutical Sciences. His interests lie in neuroscience, molecular pharmacology and the genetic basis of disease. Dr Hellyer's current research is focuses on trace amine associated receptor (TAAR1) and metabotropic glutamate (mGlu) receptors, their role in neurological disorders (especially ataxia and schizophrenia) and novel ways to target these receptors in the treatment of CNS disease.
Chair
Celine Valant
Head Of The Analytical And Structural Neuropharmacology Lab
Drug Discovery Biology, Monash University
