A New Mathematical Model for the Heat Shock Response

We present in this paper a novel molecular model for the gene regulatory network responsible for the eukaryotic heat shock response. Our model includes the temperature-induced protein misfolding, the chaperone activity of the heat shock proteins, and the backregulation of their gene transcription. We then build a mathematical model for it, based on ordinary differential equations. Finally, we discuss the parameter fit and the implications of the sensitivity analysis for our model.

[1]  Theodore R Rieger,et al.  Mathematical modeling of the eukaryotic heat-shock response: dynamics of the hsp70 promoter. , 2005, Biophysical journal.

[2]  Zihai Li,et al.  Overcoming immune tolerance to cancer by heat shock protein vaccines. , 2002, Molecular cancer therapeutics.

[3]  C A Grimbergen,et al.  A mathematical model of the hsp70 regulation in the cell. , 1998, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[4]  M. Khammash,et al.  Model validation and robust stability analysis of the bacterial heat shock response using SOSTOOLS , 2003, 42nd IEEE International Conference on Decision and Control (IEEE Cat. No.03CH37475).

[5]  J. Miller Numerical Analysis , 1966, Nature.

[6]  R. Morimoto,et al.  Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation , 1997, Molecular and cellular biology.

[7]  H. Kurata,et al.  Feedback regulation of the heat shock response in E. coli , 2001, Proceedings of the 40th IEEE Conference on Decision and Control (Cat. No.01CH37228).

[8]  John Durkin,et al.  Tools and applications , 2002 .

[9]  John C. Doyle,et al.  Surviving heat shock: control strategies for robustness and performance. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. H. Taubes,et al.  Modeling differential equations in biology , 2000 .

[11]  A Graham Pockley,et al.  Heat shock proteins as regulators of the immune response , 2003, The Lancet.

[12]  Claire J Tomlin,et al.  Understanding biology by reverse engineering the control. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  W. Press,et al.  Numerical Recipes: The Art of Scientific Computing , 1987 .

[14]  Bruce Alberts,et al.  Essential Cell Biology , 1983 .

[15]  D. G. Zill A First Course in Differential Equations: With Modeling Applications , 1951 .

[16]  Mudita Singhal,et al.  COPASI - a COmplex PAthway SImulator , 2006, Bioinform..

[17]  Akif Uzman,et al.  Essential cell biology (2nd ed.) , 2004 .

[18]  William H. Press,et al.  Numerical recipes in C. The art of scientific computing , 1987 .

[19]  P. Waage,et al.  Studies concerning affinity , 1986 .

[20]  J. Douglas Faires,et al.  Numerical Analysis , 1981 .

[21]  T. Turányi Sensitivity analysis of complex kinetic systems. Tools and applications , 1990 .

[22]  W. Wergin Essential cell biology (2nd edition). By Bruce Alberts, Dennis Bray, Karen Hopkin, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter. Garland Science/Taylor and Francis Group, New York and London (2003). ISBN 0-8153-3480-X; hardback; 740 pages illustrated; $105.00 , 2006 .

[23]  D. G. Zill A first course in differential equations with applications , 1982 .

[24]  J. Lepock,et al.  Thermal analysis of CHL V79 cells using differential scanning calorimetry: Implications for hyperthermic cell killing and the heat shock response , 1988, Journal of cellular physiology.

[25]  W. Bentley,et al.  Stochastic kinetic analysis of the Escherichia coli stress circuit using sigma(32)-targeted antisense. , 2001, Biotechnology and bioengineering.

[26]  Paul Workman,et al.  Putting the heat on cancer , 2007, Nature Medicine.

[27]  H. Kampinga,et al.  Thermotolerance in mammalian cells. Protein denaturation and aggregation, and stress proteins. , 1993, Journal of cell science.

[28]  A. Lehninger Principles of Biochemistry , 1984 .

[29]  D. Geddes,et al.  Heat shock proteins in cancer therapy. , 2000, Advances in experimental medicine and biology.

[30]  Stuart K. Calderwood,et al.  Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications , 2005, Cell stress & chaperones.

[31]  Edda Klipp,et al.  Systems Biology in Practice , 2005 .

[32]  J. Lepock,et al.  Protein denaturation in intact hepatocytes and isolated cellular organelles during heat shock , 1993, The Journal of cell biology.

[33]  N. Habib Cancer Gene Therapy: Past Achievements and Future Challenges , 2002 .

[34]  P. Waage,et al.  Ueber die chemische Affinität. § 1. Einleitung , 1879 .