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Methods for single molecule biochemistry

Research Achievements

Methods for single molecule biochemistry

Shalini Low-Nam's research focused on single particle tracking and analytical methods for single molecule biochemistry. It demonstrated a method for determining interaction kinetics of erbB dimerization on the surface of live cells. Despite a wealth of structural knowledge that suggests a model of signal initiation through the formation of back-to-back erbB dimers, kinetics within the context of the membrane remain poorly understood. To track erbB1 dynamics at the molecular level, two-color single quantum dot (QD) tracking was used to monitor resting, ligand-bound or kinase-inhibited receptors. Transition rates between free, domain-confined, and dimer states were extracted using a three-state Hidden Markov Model which uses separation of pairwise QD trajectories to determine probabilities of state transitions. In addition to providing insight into the dynamics of dimerization, this project demonstrated a role for membrane domains in promoting repeated protein-protein interactions.