WIPMMade Progress in Mathematical Modeling of Cell Fate Decisions

Toreveal the complex system behavior in cell is an important task incomputational biology. When the cells are stimulated by internal or externalsignals, the cell fate selection between different processes is very crucialfor cell life. For example, unicellular organisms make vital decisions to entervarious phases of the life cycle to adapt to environmental changes. Inmulticellular organisms, precursor cells mature into specialized cell typesduring development.

  As the most simple eukaryote, budding yeast is often used as a modelorganism to study the molecular mechanisms underlying life processes. Thereexists a detection point in cell cycle progression of budding yeast, calledStart point: the pre-Start cells are responsive to mating pheromones, whilepost-Start cells are refractory to mating pheromones and are committed toasexual (mitotic) reproduction.

  In collaboration with Prof. Xiufen Zou ( Department of Mathematics,Wuhan University), the group of data analysis and statistical computation inWuhan Institute of Physics and Mathematics, CAS has made initial progress inmathematical modeling of cell fate decision network of budding yeast. The resulthas been published online inBiophysical Journal. In this study,model-based quantitative analysis is used to explore how to maintaindistinguished cell fates between cell-cycle commitment and mating arrest inbudding yeast. The authors develop a full mathematical model of an interlinkedregulatory network based on the available experimental data. By theoreticallydefining the Start transition point, the model is able to reproduce manyexperimental observations of the dynamical behaviors in wild-type cells as wellas in Ste5-8A and Far1-S87A mutants. In addition, based on a new definition ofnetwork entropy, it is found that the Start point in wild-type cells coincideswith the system’s point of maximum entropy. This result indicates that Start isa transition point in the network entropy. Therefore, they theoreticallyexplain the Start point from a network dynamics standpoint. This result isrobust to molecular noise and network expansion.

  At the same issue in Biophysical Journal, one New and Notable (written by ProfPavel Kraikivski in Department of Life Sciences, Virginia Tech University)  is also published to highligh the above work. ProfPavel Kraikivski say that "..propose a novel way to analyze competingmolecular pathways that determine alternative cell fates, based on classicalideas from statistical physics", "If entropy turns out to be thelocomotive driving cellular decisions, then perhaps we can say that love hasits roots not only in biochemistry but also in physics”.

The article can be found below:

http://www.cell.com/biophysj/abstract/S0006-3495%2813%2900435-9

Identification of the Molecular Mechanismsfor Cell-Fate Selection in Budding Yeast through Mathematical Modeling

New and Notable：

http://www.cell.com/biophysj/fulltext/S0006-3495%2813%2900437-2

Do Cells Make Decisions Based onUncertainty in their Biochemical Networks?