"Simple two- and three-component circuits induce polarization in yeast cells.
Unlike human engineers, nature does not work from the top down. We build structures mostly according to a blueprint of the final product; but biology takes a bottom-up approach and uses local molecular interactions to construct global structures and order. Wendell Lim from the University of California in San Francisco and Chao Tang from Peking University wanted to get at the underlying rules that biological systems play by.
“We wanted to look at biological regulation from an inverse approach,” explains Lim, “not asking how one particular system performs a function of interest, but what are all the possible ways a function of interest can be accomplished.” He adds that in the post-genomic era, scientists have identified the molecular parts for many systems, but how the parts work together to accomplish a given function is much less well understood.
In particular, Lim and Tang focused on cell polarization, which Tang, a physicist, describes as “symmetry breaking via self-organization.” Their goal was to find the simplest network that accomplishes the task. Spatial organization in a cell is the key for many downstream behaviors such as motility.
*Designing Synthetic Regulatory Networks Capable of Self-Organizing Cell Polarization*
Angela H. Chau Jessica M. Walter, Jaline Gerardin, Chao Tang, and Wendell A. Lim
"How cells form global, self-organized structures using genetically encoded molecular rules remains elusive. Here, we take a synthetic biology approach to investigate the design principles governing cell polarization. First, using a coarse-grained computa- tional model, we searched for all possible simple networks that can achieve polarization. All solutions contained one of three minimal motifs: positive feed- back, mutual inhibition, or inhibitor with positive feedback. These minimal motifs alone could achieve polarization under limited conditions; circuits that combined two or more of these motifs were signifi- cantly more robust. With these design principles as a blueprint, we experimentally constructed artificial polarization networks in yeast, using a toolkit of chimeric signaling proteins that spatially direct the synthesis and degradation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Circuits with combinato- rial motifs yielded clear foci of synthetic PIP3 that can persist for nearly an hour. Thus, by harnessing localization-regulated signaling molecules, we can engineer simple molecular circuits that reliably execute spatial self-organized programs."