A Universal Tool for Unravelling the Requirements for Clinically Relevant Cell-Cell Interactions via In Situ Phenotyping and Tagging of Live Cells

PROJECT SUMMARY - ABSTRACT Cell-cell interactions drive many of today’s most challenging diseases like cancer, autoimmunity, and neurological disease. Studying cell-cell interactions is challenging because the cells are alive and remain motile, and the complexity of downstream analysis increases with every observed interaction event. Today, researchers study cell-cell interactions using invasive perturbation methods (e.g. CRISPR) or commercial spatial approaches on FFPE or FF dead tissue samples. While these approaches have their merits, the field would benefit from a non-invasive, easy-to-use method for live cell identification and on-demand tagging at scale. This proposal aims to derisk the core elements of a prototype instrument, software, and consumable developed for on-the-fly cell identification, tagging, and downstream characterization. The live-cell-in, live-cell-out process allows applications like live cell assays, further cell engineering, and new depths of multiomics discovery not possible with today’s spatial approaches. The platform will be tested in an end-user’s hands toward the clinically relevant study of the effects of antigen presentation on T-cell activation. At the core of the proposed application is the tenet that a better understanding of cell-cell interactions will expose important underlying biological pathways, thereby increasing targets for therapeutic intervention.