Friday, April 26, 2024
4/26/2024
Project Summary Direct electronic measurement of protease activity may yield signals that can be interpreted in terms of the amino acid sequence being processed by the proteasome. This proposal seeks to explore these signals (using a scanning tunneling microscope) and, from these experiments, layout the design parameters for solid state devices that can be multiplexed. As simple 2 terminal devices with no optical or electrolyte reservoirs (as required for nanopore devices) current technology should yield die with >10,000 devices, leading to possible total read speeds of 106 amino acids per second. As a single-molecule counting device, the dynamic range would be limited only by the recording time, so that a range of 109:1 may be possible. In this exploratory R21 phase, we will synthesize two types of proteasome with chemical tags that allow for incorporation into an electronic circuit, and record the current variations that occur as different peptides are processed. We will explore the processing of intact proteins when an unfoldase is also present. We will use machine learning to explore ways in which amino acid sequence information can be extracted from the stochastic electronic signals that we expect the proteasomes will produce.
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