The laboratory of single-molecule protein biophysics studies conformational dynamics of proteins using single molecule Förster resonance energy transfer (FRET) spectroscopy. Especially, we focus on intrinsically disordered proteins (IDPs) that are closely related to various human diseases. The primary goal of our research is to understand the molecular mechanisms of binding and aggregation processes of IDPs. To this end, we have been developing various experimental and analysis methods. Recently, we have investigated ultrafast association of an IDP to its binding partner. We have also studied conformational dynamics of amyloid beta monomer that is implicated in the development of Alzheimer’s disease. To probe fast association and conformational dynamics in these experiments, a photon-by-photon analysis is used, which greatly enhances time resolution of single-molecule spectroscopy. For future studies, we are developing fast three-color FRET and statistical analysis methods, which will probe the molecular details of binding and aggregation processes. Projects for summer 2019 BESIP interns to participate include:

• Development of fluorescence enhancement method using nanoantenna
• Expression and single-molecule characterizations of amyloid beta (including mutants) and their interaction partners.
• Development of custom software and analysis tools for single-molecule fluorescence instrumentation and experiments.