About the talk
Biological membranes are complex assemblies of lipids and proteins that allow cellular compartmentalization and act as the interface, through which cells communicate with each other and with the external milieu. The biological membrane constitutes the site of many important cellular functions involving transfer of information from outside to the interior of the cell. In physical terms, membranes can be treated as a complex oriented fluid which is a weakly coupled, non-covalent, and anisotropic assembly of molecules in two-dimensions (and can be treated as soft matter). G protein-coupled receptors (GPCRs) are cellular nanomachines that represent the largest group of integral membrane proteins in the human proteome involved in signal transduction across cellular membranes. GPCRs represent major drug targets in all clinical areas and account for ~40% of current drug targets. The serotonin 1A receptor is an important neurotransmitter receptor of the GPCR superfamily and is implicated in the generation and modulation of various cognitive, behavioral and developmental functions. Pioneering work from our group demonstrated that membrane cholesterol is necessary for ligand binding, G-protein coupling and signaling of serotonin 1A receptors. In our recent work, we explored the molecular basis of cholesterol sensitivity exhibited by the serotonin 1A receptor by generating site-specific mutants of key residues in CRAC motifs in transmembrane helices (TM) 2 and 5 of the receptor supported by all-atom MD simulations. These results constitute one of the first reports comprehensively demonstrating that cholesterol sensitivity could be knocked out by a single point mutation at a cholesterol binding site. Our observations are further supported from all-atom molecular dynamics simulations. I will end my talk by presenting our recent exciting observations on the role of cholesterol in GPCR endocytosis (spatiotemporal regulation) and trafficking and their implications in pathophysiology and therapeutics.
About the Speaker
Professor Amitabha Chattopadhyay is a global leader in membrane biology and is a CSIR Bhatnagar Fellow at the Centre for Cellular and Molecular Biology, Hyderabad, India. He obtained his PhD from Stony Brook University and was a Postdoctoral Fellow at the University of California, Davis. Professor Chattopadhyay’s work is focused on monitoring organisation, dynamics and function of biological membranes in healthy and diseased conditions. His group has developed and applied novel, innovative and sensitive techniques based on fluorescence spectroscopy for monitoring solvent relaxation in membranes, membrane-mimetic media, and proteins. A seminal contribution of Professor Chattopadhyay is the role of membrane cholesterol in regulating organisation, dynamics and function of G protein-coupled receptors. His contributions have been recognized by several awards including The World Academy of Sciences (TWAS) Prize, the prestigious Shanti Swarup Bhatnagar Prize, Ranbaxy Research Award and G.N. Ramachandran Gold Medal. He is an elected Fellow of TWAS, Royal Society of Biology, Royal Society of Chemistry, and all Indian Academies of Science. He authored ~350 publications with citations; 19,000 and h-index 74 (source: Google Scholar) and delivered 650 invited lectures all across the globe. Professor Chattopadhyay has mentored 22 PhD students, shaping the next generation of scientists. Professor Chattopadhyay is currently the Editor-in-Chief of The Journal of Membrane Biology and Editorial Board Member of ACS Chemical Neuroscience, FEBS Letters, Biophysical Reviews, BBA-Biomembranes and Chemistry and Physics of Lipids. He supports inclusivity and diversity in academia, has extensively traveled to various countries and likes to experience diverse cultures. He is an avid reader and storyteller, and a connoisseur of movies, music, cuisines, and cricket.
