Our broad research goal is to develop a comprehensive understanding of stochastic cellular and developmental processes, during which form and pattern emerge from the simple beginnings of a fertilized egg. In specific, we pursue questions of how clocks are designed and coordinate to produce collective behaviors with spatiotemporal accuracy during embryo development. Our research emphasizes on both the development of novel methods and applications to relevant questions. One research goal is to develop an interdisciplinary platform that enables computational search and experimental reconstitution and manipulation of biological oscillators, to determine the recurring clock network topologies and functions. The other is to understand how a pattern is formed with high spatiotemporal accuracy during zebrafish somitogenesis, through the interactions of multiple clocks, including a mitotic clock to ?tell? a cell when to proliferate and a segmentation clock to ?tell? when a somite is to form. The two research directions are interrelated. Theoretical modeling, microfluidics, and advanced imaging tools at the single molecule and single cell levels will facilitate the investigation of these phenomena.
Biological clocks exist ubiquitously in organisms ranging from bacteria to humans to establish morphogenetic patterns in embryos and maintain basic physiology in adults, and thus have a significant impact on development, differentiation, and disease. The proposed research, by deciphering the topologies and functions of individual clocks as well as the coupling mechanisms of multiple clocks, will provide valuable guidance in search of targets to treat clock-related diseases, such as cancer and embryo malformation, and improve natural clocks? performance.
| Guan, Ye; Wang, Shiyuan; Jin, Minjun et al. (2018) Reconstitution of Cell-cycle Oscillations in Microemulsions of Cell-free Xenopus Egg Extracts. J Vis Exp : |
| Guan, Ye; Li, Zhengda; Wang, Shiyuan et al. (2018) A robust and tunable mitotic oscillator in artificial cells. Elife 7: |
| Li, Zhengda; Yang, Qiong (2018) Systems and synthetic biology approaches in understanding biological oscillators. Quant Biol 6:1-14 |
| Li, Zhengda; Liu, Shixuan; Yang, Qiong (2017) Incoherent Inputs Enhance the Robustness of Biological Oscillators. Cell Syst 5:72-81.e4 |
