Abstract

Cell division is one of the most fundamental processes of life where the mother cell completely reorganizes its shape to support the partitioning of genetic information and the formation of two identical daughter cells. During this morphological transformation a large number of essential proteins have to carry out their function at specific times and subcellular locations to complete the division successfully. To achieve a mechanistic understanding of cell division process a comprehensive computational framework that is able to quantitatively analyze the dynamics of cell shape and subcellular protein distributions in an integrated manner is therefore needed. The highly deformable cell shape during cell division and cell to cell variability make this a nontrivial challenge and a comprehensive 3D computational model is still missing in the state of the art. We fill this gap by developing a 3D+time (4D) computational model of the mitotic cell in order to standardize and integrate subcellular protein distributions and quantify their spatio-temporal dynamics. This has been achieved by combining techniques from multiple disciplines: calibrated fluorescence microscopy, image analysis, spatio-temporal registration, machine learning and computational modelling. This work has established the first comprehensive computational model for the dividing human cell to standardize, integrate and mine time resolved proteomic data. This also enables building a 4D protein atlas of the dividing human cell in order to perform the systematic mapping and mining of dynamic protein distributions.

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