The overall objective of this application is to generate high-resolution, multi-omic, 3D biomolecular maps of non-diseased human organs. This group takes a Google Maps-type approach, progressing in phases to generate reference maps at increasing resolution. First, single-cell or near-single-cell resolution MS-based mapping technologies are used to provide an unbiased view of tissue molecular spatial architecture. Second, biomolecules of interest are subsequently interrogated with highly multiplexed sub- cellular resolution spatial omics assays in a targeted fashion.

The focus is on the pancreas, an essential organ important for several metabolic functions. They employ high resolving power and high-resolution mass spectrometry-based molecular mapping platforms (LMD-nanoPOT-MS) for unbiased mapping of proteins (including PTMs such as phosphorylation). These MS assays will be complemented with powerful highly multiplexed targeted spatial omics assays (CODEX and NanoString GeoMx for protein and RNA respectively) and light sheet microscopy to generate high-resolution, multi-omics human tissue maps. The innovative spatially resolved multi-omic tissue maps generated will be unprecedented and the unique multi-omic datasets will provide many novel insights. The tissue mapping efforts will be supported by commercially available and open-source state-of-the-art 3D reconstruction software to create browsable 3D RNA/protein maps of the pancreas. Undergirding the tissue characterization and 3D organ map reconstructions efforts will be a robust organ procurement, processing and distribution network.