From molecules to development: biological timing and patterning

Organisms from bacteria to humans employ complex biochemical or genetic oscillatory networks, termed biological clocks, to drive a wide variety of cellular and developmental processes for robust timing and patterning. Despite their complexity and diversity, many of these clocks share the same core architectures that are highly conserved from species to species, suggesting an essential role of network structures underlying clock functioning. The Yang lab, bridging biophysics, quantitative systems biology, and the young field of bottom-up synthetic biology, has integrated modeling with experiments in minimal cells and live embryos to elucidate universal physical mechanisms underlying these complex processes. In this talk, I will focus on our recent efforts in understanding the design and interaction of cellular clocks of cell cycles and a developmental clock to control segmentation patterns. Computationally, we have identified network motifs, notably incoherent inputs, that enhance robust performance. Experimentally, we developed artificial cells in microfluidic droplets to analyze circuits and functions of robustness and tunability. We also established single-cell assays of zebrafish embryos combined with biomechanics to analyze the role of energy and mechanical and biochemical signaling in spatiotemporal patterns.