MiV Seminar: Boxuan Zhao, University of Illinois - "Mapping the Communicatome: Sequencing-Based Technologies to Decode Cell-Cell Connections at Single-Cell Resolution"

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- NSF Expeditions - Mind in Vitro
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- Mind in Vitro: an NSF Expedition In Computing
Abstract: How cells communicate — through synapses, contact-dependent signals, and secreted factors — shapes everything from neural circuit function to tumor progression. Yet the molecular logic of most cell-cell connections remains unmapped, in part because the tools to identify which cells talk to which, and what they say, have not existed. We have developed a suite of sequencing-based technologies to address this gap. Connectome-seq (Nature Methods, 2026) maps synaptic connectivity at single-cell resolution using split-fluorescent protein reconstitution across synaptic clefts combined with RNA barcoding, enabling simultaneous identification of connected pre- and postsynaptic neurons from complex tissue. Communicatome-seq extends this framework to map diverse heterotypic cell-cell contacts — including neuron-glia and neuron-cancer interactions — using modular contact sensors that reconstitute exclusively at physical interfaces. Complementing these connectivity maps, APEX2-based proximity labeling captures the proteome and transcriptome at synaptic microdomains, revealing the molecular machinery at specific connection sites. Together, these tools provide a path toward decoding the full communicatome of the brain and beyond.
Bio: Boxuan Zhao is an Assistant Professor in the Department of Cell and Developmental Biology at the University of Illinois Urbana-Champaign, with affiliations in the Carl R. Woese Institute for Genomic Biology, the Neuroscience Program, and the Cancer Center at Illinois. His lab develops sequencing-based technologies to map cellular connectivity and communication, with applications spanning neural circuit wiring, tumor neuroscience, and epitranscriptomics. He trained with Liqun Luo and Alice Ting at Stanford for postdoc and Chuan He at the University of Chicago for PhD, and was named to the 2025 Clarivate Highly Cited Researchers list.