Exploring molecular networks directly in the cell

Abstract

The hierarchy of cell function comprises at least four distinct functional levels: genome, transcriptome, proteome, and toponome. The toponome is the entirety of all protein networks traced out directly as patterns on the single cell level in the natural environment of cells in situ (e.g. tissues). In this work a photonic microscopic robot technology (MELK) capable of tagging and imaging hundreds (and possibly thousands) of different molecular components (e.g. proteins) of morphologically-intact fixed cells and tissue have been developed. MELK data sets represent multidimensional vectors of the topologically determined arrangements of proteins within the cell. The data, assembled in a toponome dictionary of the cell, give rise to a new concept for target and drug lead discovery.