2013.8.29 From molecules to development: revealing simple rules of biological clocks
Qiong Yang, Ph.D.
Postdoctoral Fellow, Stanford University, Stanford, CA
Department of Chemical & Systems Biology
Organisms from cyanobacteria through vertebrates make use of biochemical and genetic oscillators to drive repetitive processes like cell cycle progression and vertebrate somitogenesis. Oscillators also allow organisms to anticipate natural environmental rhythms, as exemplified by the circadian clock. Despite the complexity and variety of biological oscillators, their core design is thought to be shared. Notably, most of them contain a core positive-plus-negative feedback architecture.
In this talk, I will use two dynamic systems as motivating examples, and discuss first how several modifications of a basic activator/repressor circuit can promote oscillation within individual biological clocks, and second, how multiple clocks coordinate their oscillations within single cells. In one system, we have dissected a mitotic oscillator in the Xenopus laevis early embryos, and found that the positive feedback functions as a bistable switch and the negative feedback as a time-delayed, digital switch (Yang and Ferrell, Nat Cell Biol, 2013; Ferrell, Tsai, and Yang, Cell, 2011). Mathematical modeling indicates that this time delay must be coupled to the ultrasensitivity to ensure robust oscillations and segregation of cell-cycle phases. Principles uncovered here may also apply to other activator-repressor oscillators and help in designing robust synthetic clocks. In another system, we revealed the coupling between two cell-autonomous oscillators, the circadian clock and the cell division cycle, within individual cells (Yang, Pando, et al. Science, 2010). A simple model can fit our data well and helps us to identify the molecular machinery underlying the coupling (Dong, Yang, et al. Cell, 2010).