Organogensis

VI.1 COORDINATORS
VI.2 PARTICIPANTS
VI.3 SUMMARY
VI.4 INTRODUCTION
VI.5 SPECIFIC AIMS
VI.6 BACKGROUND AND SIGNIFICANCE
VI.7 THEORETICAL FRAMEWORK
VI.8 PRELIMINARY RESULTS
VI.9 RESEARCH DESIGN AND METHODS
VI.10 RELATIONSHIP TO CYTOSKELETON (PROJECT 2) AND BIOLOGICAL NETWORKS (PROJECT 1)
VI.11 TIMELINE

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VI.10 RELATIONSHIP TO CYTOSKELETON (PROJECT 2) AND BIOLOGICAL NETWORKS (PROJECT 1)

The Organogenesis and Tissue Mechanics project integrates the aims of all three projects described in this proposal. The avian limb skeletal development and gastrulation projects, for example, must assume an underlying genetic network in each mesenchymal cell that is subject to regulation by a signaling network that contains both intracellular and extracellular components. Both the Potts model representation of the energetics of precartilage condensation and the reaction-diffusion model of morphogen patterns depend on knowledge of the articulation of these two networks-their characteristic dynamical modes and the modularity, or lack thereof, of key regulatory components of skeletogenesis. Similarly, for the mathematical representations of gastrulation, innervation, and cardiac trabeculation.

During the first two years of the project, we expect the three projects to be loosely coupled. However in the last years we intend to integrate the three projects to provide an integrated cellular to sub-cellular simulation. The computing technology for this involves Grid workflow and Department of Energy Common Component Architecture. It also involves working between the projects and other Biocomplexity efforts to establish good (XML specified) interfaces. We will prototype this coupling technology with less ambitious activities such as integration of Actin and Tubulin Cytoskeletons. This multi-project integration is an example of a synthesis that is essential for Biocomplexity. We expect different groups and different projects around the world to develop a variety of models at different levels of abstraction. The related computer science goal is to define the framework to link these together using multiple models with simulations at scales determined by the scientific fidelity required. This is not easy but the hierarchical science framework and the criterion for when to use a particular resolution are a critical concepts. We need to develop criterion as to when the sub-cellular resolution is needed and when it is an unnecessary complication. These will be the scientific questions that we will start to address in the last years of this project. We will build both the computer science coupling technology and the scientific criteria for choice into a new generation of our CompuCell framework. We can note these ideas are very familiar in partial differential equation based simulations. Multigrid methods support a hierarchy of scales with the framework automatically refining a coarse grain grid until some convergence criterion is reached. Modern cosmological simulations use a similar idea to decide when a particular clump of matter can be represented by a set of low moments or when it must be "opened-up" to reveal its fine structure. In general the new CompuCell framework will define a cross-scale interface where the modeler must specify two coupling features; firstly the criterion for use of a finer resolution model and secondly coarse graining formulae to relate the parameters and degrees of freedom across scales.