Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/78532
Title: ANALYSIS OF THE NETWORK DYNAMICS OF TRANSFORMING GROWTH FACTOR - ?1 BISTABLE ACTIVATION, WITH IMPLICATIONS ON BISTABILITY AND COMBINATION THERAPY
Authors: LI HUIPENG
Keywords: Bistability, network dynamics, TGFb1, combination therapy
Issue Date: 22-Jan-2014
Source: LI HUIPENG (2014-01-22). ANALYSIS OF THE NETWORK DYNAMICS OF TRANSFORMING GROWTH FACTOR - ?1 BISTABLE ACTIVATION, WITH IMPLICATIONS ON BISTABILITY AND COMBINATION THERAPY. ScholarBank@NUS Repository.
Abstract: A bistable switch has recently been found to regulate the activation of transforming growth factor-?1 (TGF-?1). An ordinary differential equation (ODE) model was published showing that the net activation of TGF-?1 depends on the balance between two antagonistic sub-pathways. In this thesis, I modeled perturbations that affect both sub-pathways, and simulate how their propagated effects impact the TGF-?1 system. I also studied the behaviour of the model when perturbing individual and pairwise species, and analysed robustness of combination perturbation. I found that factors such as calcium or KLF2, that can affect both the TSP1 sub-pathway and PLS sub-pathway, could have a greatly amplified effect on the feedback behavior of bistable TGF-?1 activation. Combination perturbation analysis suggested that a positive correlation between the synergy of a combination therapy, and the relative robustness of the combination doses, could be a general property of many bistable networks.
URI: http://scholarbank.nus.edu.sg/handle/10635/78532
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
LiHP.pdf7.83 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

92
checked on Feb 16, 2018

Download(s)

15
checked on Feb 16, 2018

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.