Testing a mathematical model of the yeast cell cycle.

Area of Science:

• Cell Biology
• Systems Biology
• Mathematical Modeling

Background:

• The budding yeast cell cycle is a fundamental process for cell proliferation.
• Mathematical models are crucial for understanding complex biological systems like the cell cycle.
• Accurate quantitative data is needed to constrain and validate these models.

Purpose of the Study:

• To derive and test novel predictions from a mathematical model of the budding yeast cell cycle.
• To quantitatively determine cyclin and inhibitor concentrations throughout the cell cycle.
• To compare experimental results with model predictions to identify discrepancies and refine the model.

Main Methods:

• Mathematical modeling of the budding yeast cell cycle.
• Genetic manipulation of yeast strains (e.g., lacking cdc14 and G1 cyclins).
• Quantitative measurement of cyclin and Sic1 abundance using centrifugal elutriation.
• Perturbation of the Clb-kinase oscillator and comparison with model predictions.

Main Results:

• Model correctly predicted cell cycle bistability and quantitative dependence of cell size on CLN3 gene dosage.
• Model inaccurately predicted genetic interactions between G1 cyclins and Cdh1.
• Experimental determination of concentrations for nine cyclins, Sic1, and Cdc28 provided crucial data.
• Reasonable agreement between model and experiment was observed for many perturbations, but significant discrepancies also noted.

Conclusions:

• The mathematical model serves as a strong, albeit incomplete, representation of budding yeast cell cycle control.
• Experimental validation and data generation are essential for refining predictive models of biological systems.
• Further constraints and refinements are necessary for developing a truly predictive cell cycle model.