This work package (WP) will involve a systems biology analysis of cell division in living cells. The starting points are completed genome-wide RNAi screens by means of time-lapse imaging that have identified and phenotyped in detail a set of several hundred validated mitotic genes. Here we will generate and test hypotheses about the function of these genes in the complex biological system of mitosis by: (i) performing a tertiary screen measuring three key mitotic structures in four dimensions; (ii) modelling these multiparametric, time-resolved single cell data using the tools established in WPs 5 and 6 to generate systems hypotheses about the function of single genes, gene clusters and pathways, and about novel connections between distinct pathways. Model predictions will be tested experimentally using dynamic, in vivo protein localization as well as protein-protein interaction measurements, exploiting the enabling technologies developed in WP3. Validation results will be used to refine the models, and more precise mechanistic predictions will be followed up with structure/function analyses of predicted proteins in vivo.
The standardized imaging data generated in this WP will provide the input for development of image analysis in WP2, data mining and integration in WP3, systems modelling in WP4, translational research in WP5, data aggregation and dissemination in WP7, and standardization efforts in WP6.
Jan Ellenberg (WP leader)