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How do we design biological systems as “smart medicine” that sense patients’ states, process the information, and respond accordingly? To realize this vision, we will tackle fundamental challenges across different levels of complexity, such as (1) protein components that minimize their crosstalk with human cells and immunogenicity, (2) biomolecular circuits that function robustly in different cells and are easy to deliver, (3) multicellular consortia that communicate through scalable channels, and (4) therapeutic modules that interface with physiological inputs/outputs. Our engineering targets include biomolecules, molecular circuits, viruses, and cells, and our approach combines quantitative experimental analysis with computational simulation. The molecular tools we build will be applied to diverse fields such as neurobiology and cancer therapy.