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Ongoing >> Systems Biology for System Engineers

Cell lineage

The adult nematode C. elegans consists of approximately 1000 cells (image from www.wormatlas.org) This project is about organism development from a single cell, and the main questions concern how differentiation of cells is controlled; what the principle roles of intrinsic and extrinsic signalling are; and how these are related to cell division, asymmetric determinants, transcription factors and relevant parts of the genome. Our main goal is to create system-theoretic models of the cell lineage. Based on a Boolean model that we have developed with the descriptive power to handle general cell lineages, we intend to combine this modelling technique with in silico 3D modelling of cell configuration in order to treat cell-cell influences. The embryonic Caenorhabditis elegans nematode is used as model organism since its lineage and morphology are known throughout the embryonal development.

Part of C. elegans cell lineage, replicated through a simple model. In a recent paper [Larsson, Wadströmer, Hermanson, Lendahl, and Forchheimer, Journal of Theoretical Biology 268:62-76, 2011], we have presented an extension of the classical Boolean model, intended to handle arbitrary complex cell lineages. The additions are primarily related to mechanisms that control factor levels, cell differentiation and cell division. The model is able to describe multi-level concentrations of transcription factors, as well as the dynamic behaviour of a genetic regulatory network. A benefit of the model is that it is simple to handle and that it allows direct description and generation of large cell lineage trees. The model can easily incorporate external influence from other cells or the environment. Initial results indicate that the complexity of the model in terms of number of factors and regulators is greatly reduced when incorporating external factors into the model.

C. elegans in silico, at the six-cell stage. We have also started to model the physical process of cell division and cell-cell contact within the embryo, and have made visualisation tools to study the results of such modelling. We aim to use the combination of these two modelling techniques to concisely describe the regulation that takes place in the development of C. elegans.

The group of people currently involved in this project is Robert Forchheimer, Jan-Åke Larsson, and Sofia Pettersson.

There is a Masters thesis subject available: In silico cell mechanics.

Conference papers

  • International conference on systems biology (ICSB), 2011, Mannheim/Heidelberg, "A meta-Boolean model of the Caenorhabditis elegans intestinal cell lineage" (S. Pettersson and J.-Å. Larsson)

Informationsansvarig: Martin D. Mileros
Senast uppdaterad: 2012-04-02