Labeling method for high-resolution imaging of hundreds of tissue antigens

DESCRIPTION provided by applicant Neurodegenerative diseases are among the most expensive disruptive and least well treated of human maladies arguably because they are not well understood Array tomography AT is a new method for tissue imaging with resolution in all three dimensions sufficient to resolve individual synapses and provide quantitative characterization of multple molecular constituents AT imaging data enable description of neural networks in the ontext of the three dimensional tissue architecture We believe such data will enable researchers to begin o comprehend the proper function of neural circuits and importantly to begin to undestand how it is that the various neurodegenerative processes present and progress AT is however complex and expensive and has been used in relatively few studies following the first publication in by Micheva and Smith Aratome is currently providing AT services to the research community The present application proposes proof of concept studies of a novel direct labeling method that could be the basis of a fully automated AT system analogous to a NextGen Sequencer The sample would be loaded into a microfluidic chamber placed on the imaging instrument and imaging data for tens tohundreds of antigens would be acquired automatically We would develop such an instrument as well as the catalog of directly labeled antibody and detection reagents under Phase funding PUBLIC HEALTH RELEVANCE Neurodegenerative diseases including Alzheimerandapos s and Parkinsonandapos s are becoming increasingly prevalent as the population ages Efforts to develop treatments for these diseases have been hampered by a lack of basic understanding of the disease processes due in part to the lack of technologies that provide quantitative information regarding the disease progression We propose a method for fully automated high resolution proteomic analysis of the brain to better understand these pathologies which should enable the development of more effective treatments