Title page for ETD etd-11032008-114621

Type of Document Dissertation
Author Zhang, Tongli
Author's Email Address tongli@vt.edu
URN etd-11032008-114621
Title Mathematical Models of Some Signaling Pathways Regulating Cell Survival and Death
Degree PhD
Department Genetics, Bioinformatics, and Computational Biology
Advisory Committee
Advisor Name Title
Tyson, John J. Committee Chair
Brazhnik, Paul Committee Co-Chair
Burns, John A. Committee Member
Finkielstein, Carla V. Committee Member
Li, Liwu Committee Member
Mendes, Pedro J. P. Committee Member
  • mathematical modeling
  • systems biology
  • apoptosis
  • p53
  • NFkB
Date of Defense 2008-10-23
Availability unrestricted
In a multi-cellular organism, cells constantly receive signals on their internal condition and surrounding environment. In response to various signals, cells proliferate, move around or even undergo suicide. The signal-response is controlled by complex molecular machinery, understanding of which is an important goal of basic molecular biological research. Such understanding is also valuable for clinical application, since lethal diseases like cancer show maladaptive responses to growth-regulating signals. Because the multiple feedbacks in the molecular regulatory machinery obscure cause-effect relations, it is hard to understand these control systems by intuition alone. Here we translate the molecular interactions into differential equations and recapture the cellular physiological properties with the help of numerical simulations and non-linear dynamical tools. The models address the physiological features of programmed cell death, the cell fate decision by p53 and the dynamics of the NF-?B control system. These models identify key molecular interactions responsible for the observed physiological properties, and they generate experimentally testable predictions to validate the assumptions made in the models.
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