Digital Spatial Profiler Analysis Instrument

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PROJECT SUMMARY Sanford Burnham Prebys Medical Discovery Institute (SBP) hosts ~40 labs with wide-ranging interests, spanning normal tissue stem cells, tissue homeostasis and function, neuroscience, cancer, aging and degenerative diseases of aging, including neurodegeneration. A detailed analysis of cell – cell heterogeneity and spatial organization or disorganization across a multicellular tissue is key to understanding these physiological and pathological tissue states and functions. To this end, and to stay cutting-edge, SBP requests support for a Nanostring GeoMX Digital Spatial Profiler (DSP) to enable spatially resolved, digital quantitation of proteins or mRNAs in a highly multiplexed assay on tissue sections. The GeoMX DSP will bridge spatial analyses in SBP's Histology Core (by traditional immunohistochemistry or immunofluorescence) and single cell sequencing approaches in SBP's Genomics Core. The former gives spatial information on target distribution across a tissue or tumor, but is very low plex in that only a handful a targets can be analyzed at the same time. The latter is very high plex, detecting 1000s of expressed genes in a single cell, but gives no spatial information because it starts with a tissue/tumor-derived cell suspension. The GeoMX DSP yields spatial information across the tissue or tumor but is also very high plex, detecting dozens of proteins, 1000s or RNAs or even whole transcriptome simultaneously. Protein or RNA quantitation is performed within regions of interest (ROI), defined morphologically or by expression of up to 4 protein or RNA markers of interest. ROI are flexibly defined and can, for example, be a discrete region of the tissue or a subset of cells scattered throughout the tissue. This versatile instrument permits analysis of either formalin-fixed or fresh-frozen sections, human or mouse tissues, RNA or protein analyses and targeted or unbiased whole transcriptome analyses. These traits of spatial resolution, high plex analysis and versatility make GeoMX DSP a transformative technology for SBP's major users and others. This application is supported by 10 “major users” at SBP who will take 75% of the instrument's available use time (AUT). Like any novel transformative technology, GeoMX DSP will generate previously unattainable data and insights leading to novel hypotheses, new funding and collaborations. This will enhance the research environment at SBP and our faculty's interactions and collaborations with other researchers.