Toshimichi Yamada｜ Institute of Cellular and Organismic Biology, Academia Sinica

How does multicellular structure emerge? Developmental biology analyzes how nature builds tissues. Synthetic biology engineers biological systems. We work at the intersection of the two. Our fundamental question is: what rules do cells follow to build tissues? We answer it not only by observing natural development but by reconstructing and modifying it, because changing a system is a direct test of whether we understand it.

We call the mapping between signaling-field dynamics and cell-state transitions the morphogen code. Our central hypothesis is that tissue architecture is encoded by a quantitative morphogen code, defined by the combination of signal types, signal geometry, temporal dynamics, and feedback between progenitor state and signaling sources. Using stem-cell-derived embryo models and synthetic organizer cells that deliver defined signals in space and time, we pursue three directions:

•      Decode: how natural systems read signals. We break the “signal → fate” mapping into separable layers (input, field, interpretation) and measure each one.

•      Reprogram: rewriting how tissues are patterned. We use synthetic organizer cells and engineered niches to change the signals cells receive (their identity, timing, and spatial arrangement) and to rewrite how cells interpret them.

•      Explore: beyond natural development. Using the rules we decode, we explore forms that nature has not made, and design the signals to build them.

We deliberately alternate between analysis and synthesis: we perturb single circuit elements, then put the perturbation back into a self-organizing tissue to test whether our pattern-level prediction holds. Computational models (reaction–diffusion, agent-based, Bayesian inference, deep learning) connect the two. We then use these rules to rebuild natural development, and to model how it goes wrong in disease.