Type
Text
Type
Dissertation
Advisor
Weinacht, Thomas | Wang, Jin | Averin, Dmitri | Li, Xiaolin.
Date
2015-12-01
Keywords
Physics -- Biophysics | Gene Network, Non-adiabatic, Tumor Heterogeneity
Department
Department of Physics
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76635
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Gene regulatory network is a mathematical model of gene expression and regulation in cell environment. The concept of network comes from network in math and computer science. In gene network each node is a gene that has different expression level and links between nodes represent direct regulation (activation or repression). Gene network is stochastic with intrinsic noise from biochemical reactions involved and extrinsic noise from environment. It is non-equilibrium with frequent matter/energy exchange and active entropy production. One crucial character of gene network is the involvement of multiple timescales: timescale of protein synthesis/degradation and timescale of regulation processes. Conventional studies are concentrated at adiabatic limit where regulation processes are much more frequent than protein synthesis/degradation and adiabatic approximation is valid. We explore non-adiabatic dynamics of gene network by develop a mapping from N-dimensional protein concentration space to 2N extended space using similarity to quantum mechanics and path integral. We applied our theory to self activator which is the simplest network motif. Our theory is able to explain steady states at different adiabaticity and demonstrates non-equilibrium properties like eddy current. We also studied relationship between cancer heterogeneity and non-adiabatic dynamics of core cancer network. In non-adiabatic regime, the cancer network shows alternation of phenotypic states, weaker stability, optimal transition rate and diversity of transition paths. This suggests possible source of cancer heterogeneity from non-adiabatic dynamics of core cancer network. | 114 pages
Recommended Citation
Chen, Cong, "Non-adiabatic Dynamics of Gene Regulatory Network" (2015). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2524.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2524