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E-grāmata: Mathematical Modelling of the Cell Cycle Stress Response

  • Formāts: PDF+DRM
  • Sērija : Springer Theses
  • Izdošanas datums: 08-Oct-2013
  • Izdevniecība: Springer International Publishing AG
  • Valoda: eng
  • ISBN-13: 9783319007441
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Mathematical Modelling of the Cell Cycle Stress ResponsePalielināt
  • Formāts: PDF+DRM
  • Sērija : Springer Theses
  • Izdošanas datums: 08-Oct-2013
  • Izdevniecība: Springer International Publishing AG
  • Valoda: eng
  • ISBN-13: 9783319007441
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The cell cycle is a sequence of biochemical events that are controlled by complex but robust molecular machinery. This enables cells to achieve accurate self-reproduction under a broad range of conditions. Environmental changes are transmitted by molecular signaling networks, which coordinate their actions with the cell cycle.

This work presents the first description of two complementary computational models describing the influence of osmotic stress on the entire cell cycle of S. cerevisiae. Our models condense a vast amount of experimental evidence on the interaction of the cell cycle network components with the osmotic stress pathway. Importantly, it is only by considering the entire cell cycle that we are able to make a series of novel predictions which emerge from the coupling between the molecular components of different cell cycle phases.

The model-based predictions are supported by experiments in S. cerevisiae and, moreover, have recently been observed in other eukaryotes. Furthermore our models reveal the mechanisms that emerge as a result of the interaction between the cell cycle and stress response networks.


This book details two computational models that describe the influence of osmotic stress on the entire cell cycle of S. cerevisiae.
1 Introduction
1(8)
1.1 The Cell is a Complex Dynamical System
1(1)
1.2 Cell Cycle: A System Biology Perspective
2(1)
1.3 Stress Response
3(1)
1.4 Cell Cycle Response to Stresses
4(5)
References
6(3)
2 A Biological Overview of the Cell Cycle and its Response to Osmotic Stress and the α-Factor
9(18)
2.1 Cell Cycle in Eukaryotes
9(4)
2.1.1 Cell Cycle Phases
9(1)
2.1.2 DNA Replication
10(1)
2.1.3 Mitosis and Cytokinesis
11(1)
2.1.4 Checkpoints
11(1)
2.1.5 Principles of the Cell Cycle Oscillation
12(1)
2.2 The Cell Cycle of S. Cerevisiae
13(5)
2.2.1 Principles of the Budding Yeast Cell Division
13(1)
2.2.2 The Molecular Mechanisms of the G1-to-S Transition
13(1)
2.2.3 The Molecular Mechanism of DNA Replication
14(1)
2.2.4 The Molecular Mechanism of the G2-to-M Transition
15(1)
2.2.5 The Molecular Mechanism of the M-to-G1 Transition
16(2)
2.3 Osmotic Stress Response
18(1)
2.4 Interaction Between the Cell Cycle Network and the Osmotic Stress Pathway
19(3)
2.4.1 Osmotic Stress Blocks the G1-to-S Transition
19(1)
2.4.2 Osmotic Stress Blocks the G2-to-M Transition
20(2)
2.5 Mating-Pheromone Response
22(5)
2.5.1 Pheromone Arrests the Cell Before START
23(1)
References
23(4)
3 ODE Model of the Cell Cycle Response to Osmotic Stress
27(44)
3.1 Introduction
27(1)
3.2 Modelling Procedure and Assumptions
28(4)
3.2.1 Steps to Construct the Model
28(2)
3.2.2 Hypothesised Mechanisms in the Model
30(2)
3.2.3 Mathematical Definition of the Cell Cycle Phases
32(1)
3.3 Model Description
32(13)
3.3.1 The Morphogenesis Checkpoint
32(2)
3.3.2 Regulation of Swel
34(2)
3.3.3 Regulation of Hsl 1-Hs17 Complex in the Presence of Osmotic Stress
36(1)
3.3.4 Regulation of Mih1
37(1)
3.3.5 Regulation of Cdc28-Clb2 in the Presence of Osmotic Stress
37(4)
3.3.6 Cell Growth
41(1)
3.3.7 Influence of Hog1PP on the Cyclins Transcription
41(1)
3.3.8 Regulation of Sic1 Under Osmotic Stress
42(3)
3.4 Parameter Estimation
45(1)
3.5 Model Predictions
46(15)
3.5.1 Osmotic Stress Delays the G1-to-S and G2-to-M Transitions
47(6)
3.5.2 Osmotic Stress Causes Accelerated Exit from Mitosis
53(3)
3.5.3 Delays in the G1-to-S and G2-to-M Transitions are Dose Dependent, Whereas Acceleration of the M-to-G1 Transition is Dose Independent
56(1)
3.5.4 Osmotic Stress at Late's or Early G2/M Phase Causes DNA Re-Replication
56(2)
3.5.5 Stabilisation of Sic1 by Hog1PP Drives the Mitotic Exit in MEN Mutant Cells
58(3)
3.6 Sensitivity Analysis of the Model
61(3)
3.7 Model Validation in Laboratory
64(1)
3.8 Discussion
64(7)
3.8.1 The Predictions of the Model are Supported by Various Biological Observations
65(1)
3.8.2 The Model Revealed Mechanisms for the Response of the Cell to Osmotic Stress
65(1)
3.8.3 The Relevance of the Model Predictions for Other Eukaryotes
66(1)
References
67(4)
4 Boolean Model of the Cell Cycle Response to Stress
71(18)
4.1 Introduction
71(2)
4.2 A Discrete Dynamical Model
73(2)
4.3 State Transition Space of the Cell Cycle
75(3)
4.3.1 Deriving the State Transition Matrix
76(1)
4.3.2 Dynamical Properties of the Cell Cycle State Transition Matrix
77(1)
4.3.3 Basin of Attraction
78(1)
4.4 Results
78(7)
4.4.1 Cell Cycle State Transition
78(2)
4.4.2 Osmotic Stress Drives the Cell into One of the Four Fixed Points
80(2)
4.4.3 Biological Relevance of the Size of Basins
82(1)
4.4.4 Influence of the α-Factor Synchronisation on the Cell Cycle Dynamics
82(1)
4.4.5 Osmotic Stress Can Retrieve Some Frozen States to the Cell Cycle Trajectory
83(2)
4.5 Discussion
85(4)
References
86(3)
5 Conclusion
89(4)
Appendix A List of Equations, Parameters and Initial Conditions 93(14)
Appendix B Effect of Methods of Update on Existence of Fixed Points 107
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