Markovian Approaches to Modeling Intracellular Reaction Processes with Molecular Memory


Tianshou Zhou, Sun Yat-sen University


2019.04.23 15:00-16:00


Room 306,No. 5, Science Building


Intracellular processes are biochemical and therefore stochastic. Stochastic reaction events do not necessarily occur in single steps of individual molecules, and conversely, each birth or death of a macromolecule (e.g., protein) could involve several small reaction steps, creating a memory between individual events, which leads to non-Markovian reaction kinetics. Characterizing this kinetics is challenging. Here we develop a systematic approach for a general reaction network with arbitrary waiting-time distributions, which includes the stationary generalized chemical master equation (sgCME), the stationary generalized Fokker-Planck equation and the generalized linear noise approximation. The first formulation converts a non-Markovian issue into a Markovian one by introducing effective transition rates (that explicitly decode the effect of molecular memory) for the reactions in an equivalent reaction network with the same substrates but without molecular memory. Non-Markovian features of the reaction dynamics can be revealed by solving the sgCME. The latter two formulations can be used in fast evaluation of fluctuations. These formulations can have broad applications, and in particular, they help us discovery new biological knowledge underlying memory effects. When they are applied to stochastic models of gene expression with molecular memory, we find that molecular memory is in effect equivalent to a feedback, and can induce bimodality and fine-tune the expression noise.


Tianshou Zhou, male, professor, doctoral tutor, director of the Institute of Mathematics. Research direction: Molecular Systems Biology and Computational Systems Biology. He has published more than 100 papers in SCI publications and published 2 academic monographs in Science Press. In 2008, he won the second prize of the National Natural Science Award. In 2009, he won the first prize of Nanyue Excellent Science and Technology Innovation Paper. He has presided over one key project of the National Fund Committee, one major research project and integration project of the National Fund Committee, and one project of the 973 project. Currently he serves as a member of the editorial board of five international academic journals.