MATHEMATICAL MODELING OF THE NF & KAPPAB-SIGNALING PATHWAY USING PYSB
Geena Ildefonso, Carlos Lopez.
Vanderbilt University, Nashville, TN.
Nuclear factor-KappaB (NF-κB) is a signal transduction pathway centering around transcription factors that regulate gene expression in response to environmental stimuli. Aberrant activation of NF-κB has been linked to inflammation, autoimmune diseases, and improper immune development. In addition, NF-κB has a pivotal role in the initiation and progression of several cancers. The importance of NF-κB to these pathologies has led to the development of many mathematical models over the past decade, motivated by the need to gain a detailed quantitative, and, ideally, predictive understanding of biological systems. In particular, Tay et al.'s, model successfully recapitulates key aspects of NF-κB signaling and, in turn, has yielded insights into the pathway's structure, dynamics, and function. Recently, modeling frameworks such as PySB, which construct mathematical rule-based models of biochemical systems as computer programs have emerged. PySB facilitates reusable, shareable, and transparently developed biological models. Here, we implement Tay et al.'s model of NF-κB signaling in PySB and examine the pathway's ability to control programmed cell death through regulation of anti-apoptotic signals. We also intend to link the model with other models of apoptosis and necrosis to better understand cell fate outcomes in cancers.