Spatially Resolved Molecular Measurement of Biomolecular Condensates

PROJECT SUMMARY Biomolecular condensates are diverse and abundant membrane-less organelles that partition the intracellular environment into functionally distinct compartments containing specific sets of molecules and reactions. Biomolecular condensates participate in various essential housekeeping, stress-response, or cell type-specific processes. Furthermore, an increasing number of studies have linked the physiological state of a cell or the spatial locations of condensates in a cell with the composition of the condensates. Thus, to understand the functions of biomolecular condensates, it is important to know how the molecular content in the condensates change in health vs. disease or in different spatial locations. In this proposal, we aim to develop a novel spatial genomics platform that will enable multi-modal molecular characterization of biomolecular condensates at the sub-micron scale. This will be revolutionary for studying the functional roles of biomolecular condensates in cellular processes under homeostatic and pathological conditions. Our tools will enable us to look at the genome, epigenome, and transcriptome within the condensates in a spatially resolved manner all under native cell and tissue context. We will ensure these novel genomic tools are easy to use and adopt. The successful completion of this work will lead to a comprehensive toolset for understanding cell and tissue biology from the perspective of biomolecular condensates.