Single-molecule Biophysics
Single-molecule methods are powerful techniques to study complex and diverse biological processes because of their capability to provide detailed information about molecular mechanisms, which are hidden in conventional ensemble experiments. The long-term goal of my research is to make significant contributions to understanding how complex biological entities and interactions take place at the molecular level. Understanding how the dynamic interactions between biomolecules control their assembly pathway will help us to predict potential defects in such processes caused by different diseases. These pieces of information will guide us towards the design and development of therapeutics, targeting each step of assembly.
We are working on the application and advancement of single-molecule fluorescence in the study of the conformational dynamics of G protein-coupled receptors. We also study the interactions between nucleic acids (DNA and RNA) and proteins to examine how these processes are regulated in complex cellular environments.
Conformational Dynamics of G Protein-Coupled Receptors
G Protein-Coupled Receptors (GPCRs) are the largest family of membrane proteins in the human genome that play an essential role in signal transduction. GPCRs bind a multitude of extracellular ligands (hormones, neurotransmitters, nucleotides, peptides) and undergo conformational plasticity of 7 transmembrane domains that activate signal transduction pathways in the cell. Because of their involvement in many human physiological processes, they are prominent targets for pharmaceutical drug development. Recent studies have shown that more than 35% of currently marketed drugs target these receptors. Despite their importance in human health, understanding receptor-ligand interactions at the molecular level are challenging because of technical limitations. We are using a single-molecule fluorescence (SMF) spectroscopic method to characterize the conformational dynamics of a GPCR upon interacting with distinct ligands in the native-like environment. Our studies will help in visualizing receptor-ligand interactions and receptor dynamics while they interact.
The Lamichhane Lab 