Medical Research

University of California, Davis

Johannes Hell, Kit Lam, James Ames, Manuel Navedo
Davis, CA
$1,000,000
December 2019

The exact location of proteins inside a cell is critical for their function.  Antibodies are powerful tools for protein detection and have been developed against a multitude of proteins.  However, because of their size, defining the exact location of a protein is limited to 20 nanometers (10-9 m, nm) when most protein dimensions are in the range of 4-10 nm.  Thus, to accurately map the spatial relationships between individual proteins, new technology is required for their detection.  The first goal of this project is to develop groundbreaking technology for detection of protein targets with a resolution in the 1-5 nm range.  Investigators at the University of California, Davis will do so by combining a technology for screening peptides with dyes that fluoresce only if in contact with another protein.  Their approach would generate highly specific reagents for detection of a particular protein and could also address the – often underappreciated – issue of antibodies binding to proteins other than their intended targets.  The team will use this technology to develop peptides directed against key proteins at the synapse, the contact site of neurons.  They will focus on the AMPA-type glutamate receptor (AMPAR), which mediates most of the signal transmission between neurons in the brain.  Its exact localization within synapses determines the strength of the signal transmission, which in turn can be modified under physiological conditions such as learning and under pathological conditions such as drug addiction and post-traumatic stress disorder.  Identifying the exact location of AMPARs would advance our understanding of their function in health and disease.

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