Single-molecule techniques enable high-resolution, real-time observation of individual molecules, revealing molecular heterogeneity and rare transient events that are often obscured in ensemble measurements. These approaches require minimal sample quantities and provide precise insights into dynamic molecular processes, making them powerful tools for studying complex biological and pathological systems. The overarching goal of our research group is to develop innovative bioanalytical methods that enable probing the identity, structural states, and interaction dynamics of biomolecules at the single-molecule level, ultimately toward the discovery of novel diagnostics and therapeutics. We are particularly interested in the following three major research areas.
Understanding the folding, misfolding, and interactions of intrinsically disordered proteins
Intrinsically disordered proteins (IDPs) play critical roles in cellular regulation despite lacking stable folded structures, and their dysregulation is linked to several neurodegenerative diseases. Our research program focuses on developing and applying single-molecule biophysical approaches to understand the folding/misfolding dynamics, intermolecular interactions, and nucleic acid interactions of IDPs. In particular, we investigate how post-translational modifications (PTMs) regulate the conformational landscapes, protein-protein interactions, and protein–nucleic acid interactions that govern functional assembly and pathological aggregation.- Understanding the stability and dynamics of biomolecular structures and interactions during the process of viral infections and immune responses.
Characterizing the identity, structure, and functions of biomolecules at the single-molecule level holds enormous potential for revealing detailed mechanisms of biomolecular interactions involved in host–pathogen processes. We are particularly interested in investigating the stability and dynamics of protein–protein interactions associated with viral infections and immune responses. To study these complex biomolecular interactions, we use high-resolution optical tweezers integrated with single-molecule imaging. Probing the stability, structural transitions, and intermediate states of these systems can provide fundamental mechanistic insights and help guide the development of new therapeutics.
- Development of single-molecule multiplexed diagnostics technology.
With the potential for ultimate single-molecule sensitivity, real-time signal detection, and enormous multiplexing capability, single-molecule diagnostics have the potential to transform clinical diagnostics and therapeutics in the near future. For example, highly sensitive detection of multiple biomarkers within the same biological sample can significantly improve the accuracy of disease diagnosis as well as treatment monitoring for cancers and neurodegenerative diseases. We are interested in developing DNA nanotechnology-based strategies to make single-molecule diagnostics simple, high-throughput, and broadly accessible while maintaining robust multiplexing capability.