Cytoskeleton and Cell Motility

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V.7 Relation with Organogenesis (project 3) and Biological Networks (project 1):

Although the experiments described above are self-contained, they relate intimately to the problems addressed in Projects 3 and 1 ("Organogenesis" and "Biological Networks"). Morphogenetic change depends to a large degree on processes which introduce asymmetry and polarity in cells and groups of cells. Cell-level asymmetries occur because of asymmetries at the subcellular level - nonrandom localization of particular membrane proteins, localized activation of cell motility machinery - and their development depends on the complex intracellular signaling apparatus. The subcellular asymmetries, and the accompanying signaling mechanisms and indeed cell organization itself, depend in particular, on the actin and tubulin cytoskeletons. Therefore, a quantitative and predictive understanding of development and organogenesis, ultimately requires understanding the properties of the actin and tubulin cytoskeletons.

The cytoskeleton project applies to the Biological Networks project because the cytoskeleton is itself a biological network. We will use network analysis to examine the cytoskeleton as a whole, to contribute to our global understanding of the cytoskeleton and its properties and role in vital cell functions (e.g. signaling). Second, the analysis of protein-interaction networks will also contribute to our specific understanding of cytoskeletal mechanics because it will help to identify previously uncharacterized cytoskeletal proteins and interactions between known proteins. Finally, our experiments and modeling cytoskeletal behavior will feedback to our Network analysis, with experiments and observations that can test its conclusions.

As discussed in Section VI.10, we will integrate the three projects together in a cross-scale simulation from cellular aggregation to subcellular structure in the last three years of the project.