Inferring a system model of subcellular topoisomerase II beta localization dynamics.
Measuring the mobility of proteins in living cells has become critical to many studies in cell biology and forms the basis for discussion on sub-cellular dynamics. Increasingly localization networks are being put together into compartment models to represent the exchange of molecules, represented mathematically as ordinary differential equations (ODE). The set-up is based on published literature, the "knowledge" of the investigator and 3D visualization of the data. Here we demonstrate this method on the example of a simple distribution model of the molecule Topoisomerase II beta (Topo II beta), nuclear protein that modifies DNA topology. It is found in high concentration in the nucleolus and diffuse in the nucleoplasm, demonstrating a non-membranous inhomogeneity in its distribution. We expand on the simple model by adding additional components to fit fluorescence recovery after photobleaching (FRAP) experiments for protein (GFP) labeled Topo II beta to measure its mobility. This model is then validated by comparing it with alternative scenarios and shown to have predictive power.
Intelligent Bioinformatics Systems, German Cancer Research Centre (DKFZ), Heidelberg, Germany. cathale@partners.org
Chaitanya A
CA
Athale
Morten O
MO
Christensen
Roland
R
Eils
Fritz
F
Boege
Christian
C
Mielke
D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D008433:Mathematics; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; D004250:DNA Topoisomerases, Type II