We develop and use integrated approaches for spatiotemporal, multimodal measure and control of complex living systems from molecules to tissues. We recently created protein-based sensors and actuators for chemical sensing and chemogenetic or optogenetic manipulation of cell behaviors in behaving animals. We developed polony gel (clonal DNA cluster array of ≤ 1-µm features)-based spatial barcoding and sequencing to spatially map single-cell transcriptomes and proteomes in intact tissues to study physiological, pathological, and pharmacological changes. Techniques frequently used in current projects include protein display and high-throughput screening, polony gel fabrication and sequencing, Pixel-seq, SMI-seq, mass spectrometry, and fluorescence imaging. We are applying new tools to study cellular senescence in tissues and brain mechanisms of chronic pain and addiction, to improve safety and efficacy of gene and cell therapies, and to guide the evolution of multi-enzyme machinery making high-value chemicals. Below is a summary of ongoing projects: