Simple, realistic models of complex biological processes: positive feedback and bistability in a cell fate switch and a cell cycle oscillator.
Here we review some of our work over the last decade on Xenopus oocyte maturation, a cell fate switch, and the Xenopus embryonic cell cycle, a highly dynamical process. Our approach has been to start with wiring diagrams for the regulatory networks that underpin the processes; carry out quantitative experiments to describe the response functions for individual legs of the networks; and then construct simple analytical models based on chemical kinetic theory and the graphical rate-balance formalism. These studies support the view that the all-or-none, irreversible nature of oocyte maturation arises from a saddle-node bifurcation in the regulatory system that drives the process, and that the clock-like oscillations of the embryo are built upon a hysteretic switch with two saddle-node bifurcations. We believe that this type of reductionistic systems biology holds great promise for understanding complicated biochemical processes in simpler terms.
Ferrell
James E
JE
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA. james.ferrell@stanford.edu
Pomerening
Joseph R
JR
Kim
Sun Young
SY
Trunnell
Nikki B
NB
Xiong
Wen
W
Huang
Chi-Ying Frederick
CY
Machleder
Eric M
EM
D000818:Animals; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D004625:Embryo, Nonmammalian; D004789:Enzyme Activation; D025461:Feedback, Physiological; D016193:G1 Phase; D053858:Metabolic Networks and Pathways; D023421:Models, Animal; D009865:Oocytes / Q000502:physiology*; D014982:Xenopus laevis
D016203:CDC2 Protein Kinase