Single-molecule techniques enable high-resolution, real-time observation of individual molecules, revealing heterogeneity and rare molecular events. They minimize the amount of sample requirements, eliminate ensemble averaging, and provide precise insights into dynamic molecular processes, making them essential techniques for studying complex biological and pathological processes. The overarching goal of our research group is to develop bioanalytical methods that enable probing the identity, structural states, and interaction dynamics of biomolecules at single-molecule level. This aims towards discovering novel diagnostics and therapeutics. We are particularly interested in the following three main areas.
- Understand 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 single-molecule level holds enormous potential to reveal detailed mechanism of biomolecular interactions involved in host-pathogen interactions. We are particularly interested to investigate the stability and dynamics of protein-protein interactions involved in the mechanism of viral infections and immune responses. We use high-resolution optical tweezers integrated with single-molecule imaging to study these complex biomolecular interactions. Probing the stability and dynamics of structural transitions and intermediate states can provide new insights toward discovering new therapeutics.
- Understand the folding/misfolding of proteins to induce protein aggregations
Protein aggregation inside the neuron cells have been the major cause of several neurodegenerative diseases including Parkinson’s Disease (PD) and Alzheimer’s Disease (AD). In general, these proteins are intrinsically disordered proteins (IDP) that they do not have regular folded structures. Several factors including chemical modifications (called Post Translational Modifications) in certain amino acid residues in those proteins are known to induce such aggregations. We are interested in developing single-molecule techniques to understand the folding/misfolding dynamics and the cause of aggregation.
- Development of single-molecule multiplexed diagnostics technology.
With the potential for ultimate single-molecule sensitivity, real-time signal detections, and enormous space for multiplexing, single-molecule diagnostics can transform clinical diagnostics and therapeutics in the near future. For example, highly-sensitive detection of multiple biomarkers in the same biological sample can significantly improve the accuracy in not only diagnosis and but also in monitoring the treatment of cancers and neurodegenerative diseases. We are interested in investigating the strategies based on the concepts of DNA nanotechnology to make single-molecule diagnostics simple, and high-throughput with multiplexing capability.