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Single-Molecule Approach to Molecular Binding on Supported Lipid Bilayers

Xun Yin

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Date and time:��

Tuesday, December 2, 2014 - 10:30am

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Grandview Conference Room at 1320 Grandivew Ave

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Many biological processes involve specific, well-determined interactions between complementary molecules displayed on membrane surfaces. In this project, we construct a DNA-mediated membrane binding model to mimic real receptor dimerization that could cause HER2-positive breast cancer. Using single-molecule tracking in conjunction with fluorescence resonance energy transfer, we aim to offer insights into the mechanism of transport of biological molecules that could hopefully control and inhibit HER2 dimerization. However, inferring complex stochastic motion models from single-particle trajectories in an objective manner is nontrivial due to noise from sampling limitations and biological heterogeneity. In addition to traditional mean square displacement (MSD) based analysis, we borrow a systematic Bayesian approach to multiple hypothesis testing of a general set of competing motion models based on particle MSDs that automatically classifies particle motion, properly accounting for sampling limitations and correlated noise while appropriately penalizing model complexity according to Occam’s Razor to avoid over-fitting. We wish to demonstrate the utility of this approach by applying it to our system, making it ideal for classifying the complex motion of large numbers of single molecules and cells from high-throughput screens, as well as single-cell-, tissue-, and organism-level studies.