The cofilin activity pathway in metastasizing mammary tumour cells

• Main Author: Prosk, Erin
• Language: English
• Published: University of British Columbia 2009
• Online Access: http://hdl.handle.net/2429/12640

The activity of cofilin has been identified as a critical determinant of the metastatic potential of carcinoma cells in vivo. The burst of cofilin-mediated barbed end production following stimulation of a cancer cell with EGF is not yet completely understood. This motivates the use of mathematical models to test experimental hypotheses and propose areas for future experimental consideration. In this thesis, I outline the initial temporal models of the cofilin activity pathway in metastasizing mammary tumour cells developed by myself and my supervisor Leah Edelstein-Keshet. This work results from a collaboration with experimentalist Dr. John Condeelis (Albert Einstein College of Medicine of Yeshiva University). The project is hierarchical, building from a reduced model of cofilin-barbed end interaction (Chapter 2), to include distinct cofilin forms (Chapter 3) and compartmental considerations (Chapter 4). In each model, we investigate essential mechanisms of the cofilin pathway required to reproduce the barbed end peak observed in experiment. The models presented in Chapters 2-4 represent the initial step in the modeling analysis of the cofilin activity pathway. The work serves to validate current hypotheses about the cofilin activity pathway and identify important interactions and considerations for future experimental and theoretical development.