Tuning the Xenopus mitotic oscillator in artificial cells

We study biological oscillations and self-organization phenomena in both artificially constructed mitotic cells and live zebrafish embryos. We focus on how the network structures of biological clocks are linked to their functions, such as tunability and robustness, and how individuals coordinate through biochemical and mechanical signals to generate collective spatiotemporal patterns. To pin down the physical mechanisms that give rise to these complex phenomena, we integrate modeling, time-lapse fluorescence microscopy, microfluidics, and systems and synthetic biology approaches.
Although central architectures drive robust oscillations, networks containing the same core vary drastically in their potential to oscillate. We computationally generate an atlas of oscillators and found that, while certain core topologies are essential for robust oscillations, local structures substantially modulate the degree of robustness. Strikingly, two key local structures, incoherent inputs and coherent inputs, can modify a core topology to promote and attenuate its robustness, additively (Cell Systems 2017). Experimentally, we developed an artificial cell-cycle system to mimic the real mitotic oscillations in microfluidic droplets (eLife 2018). The artificial cells can perform self-sustained oscillations for 40 cycles over multiple days. The oscillation period and number of cycles can be reliably tuned by the amount of clock regulators or droplet sizes. Such innate flexibility makes it key to studying clock functions of tunability and stochasticity at the single-cell level. With nanofabrication and long-term time-lapse fluorescence microscopy, this system enables a high-throughput, single-cell analysis of clock dynamics and functions. We now combine this platform with mathematical modeling to elucidate the topology-function relation of biological clocks.