Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


case1323278159.pdf (13 MB)

ETD Abstract Container

Abstract Header

Computational Models of the Mammalian Cell Cycle

Weis, Michael Christian
http://rave.ohiolink.edu/etdc/view?acc_num=case1323278159

Abstract Details

2011, Doctor of Philosophy, Case Western Reserve University, EECS - System and Control Engineering.
Systems biology has sometimes been defined as the application of systems science and engineering concepts to biological problems. This dissertation illustrates the usefulness of this approach in understanding the regulation of the mammalian cell cycle. Cell growth and division are fundamental properties of life, and the dysregulation of cell cycle control is central to the development of cancer. Understandably then, the cell cycle has historically been a popular subject for mathematical modeling efforts and we review 154 models developed over the past 80 years. Beyond mathematics however, understanding systems requires the evaluation of models against data. The work presented herein illustrates an approach for estimating the median dynamic expression profiles of cell cycle regulatory molecules from a flow cytometric snapshot of an asynchronous population, and applies this data to the modification and calibration of a computational model of mammalian cell cycle control. This contribution illustrates the value of the systems biology approach in integrating existing evidence, interpreting data, and driving new hypotheses regarding the organizing principles of biological systems. Having used single cell data to model the median trajectory of a population, we then investigate approaches to simulate cell-cell variation and reproduce the distribution of cells originally measured with flow cytometry. This comprehensive methodology also establishes an approach to studying proliferative diseases, such as hematopoietic cancers, which can be easily sampled and measured using flow cytometry. As only one static measurement is needed to define the underlying expression profile, this may provide an entry point to applying computational models and systems engineering methodologies to the treatment of individual patients.
Sree N. Sreenath, PhD (Committee Chair)
James W. Jacobberger, PhD (Committee Member)
Kenneth A. Loparo, PhD (Committee Member)
Vira Chankong, PhD (Committee Member)
Mihajlo D. Mesarovic, PhD (Committee Member)
205 p.
Applied Mathematics; Bioinformatics; Biology; Engineering; Molecular Biology; Systems Science
systems biology; computational biology; mathematical biology; cell cycle; molecular biology

Recommended Citations

Citations

  • Weis, M. C. (2011). Computational Models of the Mammalian Cell Cycle [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1323278159

    APA Style (7th edition)

  • Weis, Michael. Computational Models of the Mammalian Cell Cycle. 2011. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1323278159.

    MLA Style (8th edition)

  • Weis, Michael. "Computational Models of the Mammalian Cell Cycle." Doctoral dissertation, Case Western Reserve University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1323278159

    Chicago Manual of Style (17th edition)

case1323278159
2,235
© 2011, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.