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Single-Molecule Biophysics

Rajan Lamichhane Rajan Lamichhane first learned about state-of-the-art single-molecule biophysics while working on his PhD in biochemistry and biophysics at Wayne State University. He uses the technique to study protein-nucleic acid interactions, RNA folding, protein dynamics, and protein functions.

“I like single-molecule methods because they are powerful techniques to explore complex and diverse biological processes at the molecular level,” says Lamichhane, an assistant professor in the UT Department of Biochemistry and Cellular and Molecular Biology (BCMB). “Biomolecule interactions and assembly control all aspects of biological activities in the cell and are directly linked with human health. Understanding these processes will help us predict potential defects that cause diseases and will ultimately guide us towards designing therapeutics to cure these diseases.”

Lamichhane joined BCMB in 2018 and brought a welcome addition to the department in the areas of biophysics and membrane biology with a focus on understanding receptor function and molecular dynamics using single-molecule techniques. He teaches BCMB 401: Biochemistry I and BCMB 511: Advanced Protein Chemistry and Cellular Biology and enjoys interacting with his students and learning about their experiences.

“The most exciting part of teaching is seeing the students’ faces when they understand something new,” Lamichhane says. “One thing that always makes me proud of being a teacher is watching my students grow academically and move forward with their career goals.”

In his lab, Lamichhane and his students are working on the application and advancement of single-molecule fluorescence to study integral membrane proteins called G protein-coupled receptors (GPCRs), which are involved in many physiological processes.

“There are more than 800 GPCRs encoded in the human genome, which makes them good targets for treating many diseases,” Lamichhane says. “More than 35% of marketed drugs target these receptors. GPCRs bind many types of ligands on their extracellular face and undergo conformational changes of the seven-transmembrane domain to activate signal transduction pathways inside the cell to produce a physiological response.”

Students in his lab have a basic knowledge of physics, biology, and chemistry, but also must have an understanding of molecular biology and biochemistry since they deal with biological samples.

“This method requires extensive sample modifications, such as putting probes, or fluorophores, at a particular position in biomolecules, which requires an understanding of structural biology and chemistry,” says Lamichhane, who studied chemistry and biology during his undergraduate and graduate studies at Tribhuvan University in Nepal.

Lamichhane uses single-molecule microscopy to characterize the conformational dynamics of a GPCR when it interacts with distinct ligands. Despite their importance in signaling, scientists do not fully understand ligand-based conformational changes of transmembrane domains.

“It is crucial to understand this mechanism to enhance our ability toward GPCR-based drug discovery,” Lamichhane says. “These studies will allow us to visualize receptor-ligand interactions and receptor dynamics while they interact. I hope my research will help in advancing single-molecule techniques to address fundamental questions and needs in basic biomedical science.”