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Probing Protein-Protein Interactions with High-Throughput GMR Protein Arrays (NIH)

Principal Investigators: Shan X. Wang, PJ Utz, Lino Gonzalez, Jr.

Identifying and characterizing protein-protein interactions and entire interaction networks is the key to understanding drug targeting or side effects, but major hurdles remain. We propose to create a non-optical array-based approach for ultrasensitive investigation of protein-protein interactions relevant to therapeutic response and drug discovery. The ultra-sensitivity (~femtomolar) will be provided by the giant magnetoresistance (GMR) biosensors previously developed in Wang Lab and Stanford Center for Cancer Nanotechnology Excellence (CCNE). Better specificity and faster assay time will be achieved due to much better signal to noise ratios. Deep multiplexing to probe tens of thousands of proteins is possible with large scale GMR sensor array. By using high avidity (multivalent) magnetic nanotags, we will be able to detect transient low affinity extracellular protein-protein interactions as multiple ECDs (baits) can react with multiple binding sites of prey proteins simultaneously. We will engineer giant magnetoresistive (GMR) biosensors with femtomolar sensitivity in a high-throughput array format.