Effects of Stochasticity in Biological Oscillators

Many processes need to occur periodically for proper functioning of the cell, despite fluctuations in its environment. A cell must remain robust against irrelevant fluctuations, while simultaneously responding to relevant cues. We study how network topologies optimize the trade-off between maintaining robust oscillations and biosynthetic expenditure.

Many studies concur that motifs with positive and negative feedback are most robust to variations in the deterministic limit [1, 2], and in the stochastic regime [3, 4]. However, there is no mechanistic understanding for predicting the performance of different topologies.

Our findings suggest that deterministic amplitude, along with the distribution of angular velocities along the phase-space orbit of dynamical variables can lead to a mechanistic understanding of this trade-off. Regulation mechanisms and tuning of interaction strengths play a pivotal role in this optimization.

[1] Tsai TY, Choi YS, Ma W, Pomerening JR, Tang C, Ferrell JE Jr, Science, 2008, Jul 4.
[2] Zhengda Li, Shixuan Liu, Qiong Yang, Cell Systems, Vol 5, Issue 1, 26 July 2017.
[3] Woods ML, Leon M, Perez-Carrasco R, Barnes CP, ACS Synth. Biol., 2016, 5(6), pp 459-470
[4] Vilar JMG, Kueh HY, Barkai N, Leibler S, Proc Natl Acad Sci USA. 2002 Apr 30; 99(9):5988-5992