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The adaptive responses of a living cell to internal and external signals are controlled by networks of proteins whose interactions are so complex that the functional integration of the network cannot be comprehended by intuitive reasoning alone. Mathematical modeling, based on biochemical rate equations, provides a rigorous and reliable tool for unraveling(More)
The physiological responses of cells to external and internal stimuli are governed by genes and proteins interacting in complex networks whose dynamical properties are impossible to understand by intuitive reasoning alone. Recent advances by theoretical biologists have demonstrated that molecular regulatory networks can be accurately modeled in mathematical(More)
Cellular rhythms are generated by complex interactions among genes, proteins and metabolites. They are used to control every aspect of cell physiology, from signalling, motility and development to growth, division and death. We consider specific examples of oscillatory processes and discuss four general requirements for biochemical oscillations: negative(More)
In recent years, molecular biologists have uncovered a wealth of information about the proteins controlling cell growth and division in eukaryotes. The regulatory system is so complex that it defies understanding by verbal arguments alone. Quantitative tools are necessary to probe reliably into the details of cell cycle control. To this end, we convert(More)
The molecular machinery of cell cycle control is known in more detail for budding yeast, Saccharomyces cerevisiae, than for any other eukaryotic organism. In recent years, many elegant experiments on budding yeast have dissected the roles of cyclin molecules (Cln1-3 and Clb1-6) in coordinating the events of DNA synthesis, bud emergence, spindle formation,(More)
After anaphase, the high mitotic cyclin-dependent kinase (Cdk) activity is downregulated to promote exit from mitosis. To this end, in the budding yeast S. cerevisiae, the Cdk counteracting phosphatase Cdc14 is activated. In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. During anaphase, Cdk- and Polo-dependent phosphorylation of(More)
To contribute to a deeper understanding of M-phase control in eukaryotic cells, we have constructed a model based on the biochemistry of M-phase promoting factor (MPF) in Xenopus oocyte extracts, where there is evidence for two positive feedback loops (MPF stimulates its own production by activating Cdc25 and inhibiting Wee1) and a negative feedback loop(More)
Complex assemblies of interacting proteins carry out most of the interesting jobs in a cell, such as metabolism, DNA synthesis, movement and information processing. These physiological properties play out as a subtle molecular dance, choreographed by underlying regulatory networks. To understand this dance, a new breed of theoretical molecular biologists(More)
p53 is activated in response to events compromising the genetic integrity of a cell. Recent data show that p53 activity does not increase steadily with genetic damage but rather fluctuates in an oscillatory fashion. Theoretical studies suggest that oscillations can arise from a combination of positive and negative feedbacks or from a long negative feedback(More)
Much is known about the genes and proteins controlling the cell cycle of fission yeast. Can these molecular components be spun together into a consistent mechanism that accounts for the observed behavior of growth and division in fission yeast cells? To answer this question, we propose a mechanism for the control system, convert it into a set of 14(More)