In Fall 2018, CMSA will focus on a program that aims at recent mathematical advances in describing shape using geometry and statistics in a biological context, while also considering a range of physical theories that can predict biological shape at scales ranging from macromolecular assemblies to whole organ systems.
The first workshop will focus on the interface between Morphometrics and Mathematics, while the second will focus on the interface between Morphogenesis and Physics.The workshop is organized by L. Mahadevan (Harvard), O. Pourquie (Harvard), A. Srivastava (Florida).
Speaker: Leonardo Morsut
Title: Programming self-organization of multicellular structures with synthetic cell-cell signaling coupled to morphogenetic effectors
Abstract: During embryonic development, complex multicellular tissues form based on genetically encoded algorithms that specify how cells will behave both individually and collectively. We develop synthetic biology tools and approaches to implement in cells such self-organization programs and understand their overall logic.
Extensive studies of natural developmental programs have implicated many genes that control cell-cell signaling and cell morphology. Despite their molecular diversity, a common theme in these developmental systems is the use of cell-cell signaling interactions to conditionally induce morphological responses. Thus, we explored whether simple synthetic circuits in which morphological changes are driven by cell-cell signaling interactions could suffice to generate self-organizing multicellular structures. As a modular platform for engineering new, orthogonal cell-cell signaling networks, we focused on using the synthetic notch receptor system, which allows a cell to detect molecular signals from its neighbors and, in response, to induce user-specified transcriptional programs. As morphological effectors, we focused on changes in cell-adhesion in fibroblasts, by changing expression of cadherin molecules. Despite their simplicity, these programs can drive the spontaneous generation of multicellular structures in 3D with key hallmarks of natural developmental systems: they can self-organize into multilayer structures, form through sequential steps, display divergence of genotypically identical cells into distinct cell types, break symmetry, and they can regenerate upon injury. Through computational modeling, we show how these trajectories allow the multicellular system a more exhaustive exploration of the space of forms (morphospace), when compared to systems with signaling only, or with sorting only. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.
