Synthetic ‘Tissues’ Build Themselves

UCSF | Nicholas Weiler

Synthetic ‘Tissues’ Build Themselves Biologists Program Cells to Self-Organize into 3D-Structures in a First Step Towards Tissues that Regrow and Self-Repair

Researchers programmed cells to self-assemble into complex structures such as this one with three differently colored layers. Credit: Wendell Lim/UCSF 
How do complex biological structures — an eye, a hand, a brain — emerge from a single fertilized egg? This is the fundamental question of developmental biology, and a mystery still being grappled with by scientists who hope to one day apply the same principles to heal damaged tissues or regrow ailing organs.

Now, in a study published May 31, 2018 in Science, researchers have demonstrated the ability to program groups of individual cells to self-organize into multi-layered structures reminiscent of simple organisms or the first stages of embryonic development.

“What is amazing about biology is that DNA allows all the instructions required to build an elephant to be packed within a tiny embryo,” said study senior author Wendell Lim, PhD, chair and Byers Distinguished Professor in the Department of Cellular and Molecular Pharmacology at UCSF, director of the NIH-funded Center for Systems and Synthetic Biology, and co-director of the National Science Foundation–funded Center for Cellular Construction. “DNA encodes an algorithm for growing the organism — a series of instructions that unfolds in time in a way we still don’t really understand. It’s easy to get overwhelmed by the complexity of natural systems, so here we set out to understand the minimal set of rules for programming cells to self-assemble into multicellular structures.”

A critical part of development is that, as biological structures form, cells communicate with one another and make coordinated, collective decisions about how to structurally organize themselves. To mimic this process, the new research — led by UCSF postdoctoral researcher Satoshi Toda, PhD, in Lim’s lab — relied on a powerfully customizable synthetic signaling molecule called synNotch (for “synthetic Notch receptor”) recently developed in Lim’s lab, which allowed the researchers to program cells to respond to specific cell–cell communication signals with bespoke genetic programs. Continue reading