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Complex Systems Biology of Mammalian Cell Cycle Signaling in Cancer

Avva, Jayant
http://rave.ohiolink.edu/etdc/view?acc_num=case1295625781

Abstract Details

2011, Doctor of Philosophy, Case Western Reserve University, EECS - System and Control Engineering.
We present here a complex systems biology approach towards elucidating the role of mammalian cell cycle signaling in cancer. In this context, availability of copious amounts of biological data has done little to alter the paucity of contextually consistent dynamic time profile data, necessary for the calibration and validation of dynamic models of the biological systems. Such computational models form the heart of the complex systems biology approach, and paucity of appropriate data is an immediate impediment. To address this problem, we developed a novel methodology to filter measurement noise and extract time profile variation of cell cycle biochemicals from statically sampled flow cytometry data. Taking a hierarchical viewpoint, a mathematical model of the upstream signaling from the receptor through to the nucleus was developed. A computational model of the downstream cell cycle control system based on a modified Tyson’s mathematical model that uses our time profile extraction methodology for calibration was also developed. The approach was demonstrated separately using K562 and MOLT4 cell line experimental data from the wetlab. We built custom software, CytoSys, to facilitate the application of our methodology.
Sree N. Sreenath, PhD (Committee Chair)
James W. Jacobberger, PhD (Committee Member)
Mihajlo D. Mesarovic, PhD (Committee Member)
Kenneth A. Loparo, PhD (Committee Member)
Vira Chankong, PhD (Committee Member)
Cellular Biology; Engineering; Systems Science
systems biology; time profile; cell cycle control system model; computational biology

Recommended Citations

Citations

  • Avva, J. (2011). Complex Systems Biology of Mammalian Cell Cycle Signaling in Cancer [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1295625781

    APA Style (7th edition)

  • Avva, Jayant. Complex Systems Biology of Mammalian Cell Cycle Signaling in Cancer. 2011. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1295625781.

    MLA Style (8th edition)

  • Avva, Jayant. "Complex Systems Biology of Mammalian Cell Cycle Signaling in Cancer." Doctoral dissertation, Case Western Reserve University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1295625781

    Chicago Manual of Style (17th edition)

case1295625781
1,209
© 2011, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.