Development of a Single-neuron Protein Mass Analyzer: New Frontiers for Neuroscience
George Washington University
The ability to understand molecular events in single neurons would be transformative in deciphering the functioning of the brain, but this requires new analytical technologies, particularly those capable of measuring the proteome and metabolome of individual mammalian cells. The Nemes Research Group focuses on the development of next-generation mass spectrometry to enable the label-free characterization of broad types of metabolites, peptides, and proteins in single cells. In this contribution, a 'proteomic single-neuron mass analyzer' will be developed by integrating recent advances in technology where they exist and introducing new technologies where they do not to transform high-resolution tandem MS from a traditionally population-averaging tool to one capable of measuring single cells. Research goals toward this end are to allow for microsampling mammalian neurons, extracting and rapidly digesting their proteins, as well as separating, ionizing, and quantifying the resulting molecules to query protein expression. This new MS technology will be used to establish the proteomic variability of individual mammalian cortical neurons, raising an opportunity to lay down the foundation of quantitative, proteomic data-driven classification of neurons. The instrument and data resulting from this work will be disseminated to broad user bases in the life sciences to help find answers to leading questions in basic and applied fields but also to pose new directions toward advancing technology, knowledge, and human health.