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Title: Effects of external fluctuations on the stochastic dynamics of gene regulatory networks
Author: Gupta, Abhishek
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2020
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In systems biology, intracellular gene expression networks are modelled as mass balance chemical reactions. These schematic pathways are often simplified and miss significant details such as intermediate templates or enzymatic components, essentially needed in vivo. In our analysis, we explore further improvements in reach of these parsimonious models with inclusion of intermediate species as external components. Using stochastic simulations and complementary analytical methods, we compare mesoscopic behaviour of stand-alone original models and their interactions with external components. Implementing different examples of gene expression mechanisms, we demonstrate importance of upstream transcriptional noise as well as downstream fluctuations in protein degradations which are often ignored. We use transition in bimodal distributions as a germane tool to demonstrate these effects. Another pertinent example is our study on amplification of correlation resonance due to upstream transcription in a two protein translation network with proteolytic enzyme sharing. In conclusion, in this thesis, we try to bolster significance of underlying mechanistic details in modelling intracellular processes as well as emphasize pro and cons of different analytical approximation tools used in this study.
Supervisor: Grima, Ramon ; Swain, Peter Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: approximate theoretical analysis ; stochastic behaviour ; models ; gene expression ; bimodality ; Correlation Resonance ; approximation analytical methods ; templates