The cell is a complex biological network that is capable of transitioning to a wide variety of states. Enumerating, defining, and understanding the mechanisms behind cellular states are important problems of Systems Biology. This document contains insights gleaned from the study of three systems wide problems: transcription regulation by NF-kB, oxidative stress in response to reactive oxidative species, and gene expression changes caused by creation of lentiviral mediated cancer models. A consideration by literature review is provided of the historical problem formulations for studying mechanisms of NF-kB target gene regulation. Previous formulations of regulation are useful as frameworks for experimental design of future experiments when considered without bias towards prior assumptions. A description of the construction of a network bridging the multitude of cell responses to hydrogen peroxide is provided along with failed attempts to validate that network. Potential regulation by heme in response to oxidative stress reveals an ever tighter relationship between ROS, metabolism, and cell death. Application of molecular signatures defined from human primary cancers is used for determining the suitability of mouse cancer models generated from lentiviral constructs for the study of human primary cancers. Mouse tumors generated artificially display a surprising degree of concordance with primary cancers. The ability of high throughput technologies to query nearly the entire state of the cell can lead to undesirable complexity. Application of simplifying assumptions derived from the consideration of the biological fundamental problem as opposed from technical limitations allows a reduction of in complexity that elucidates areas for future study.
|Advisor:||Subramaniam, Shankar, Verma, Inder|
|Commitee:||Cavenee, Webster, Hoffmann, Alexander, Ren, Bing|
|School:||University of California, San Diego|
|School Location:||United States -- California|
|Source:||DAI-B 73/11(E), Dissertation Abstracts International|
|Subjects:||Cellular biology, Bioinformatics, Oncology|
|Keywords:||Cancer, Cellular networks, NF-kB, Oxidative stress, Transcription regulation|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be