Gene-O-Matic is a graphical tool for the construction and simulation of regulatory networks in multicellular organisms. It was developed keeping in mind that researchers should be able to focus on their experiments rather than learning to use complex computer programs. Therefore, the focus was put on a simple user interface for entering the network and the cells to simulate. The simulation can be observed in real time in 3D view. During the simulation, cells grow, move in 3D space, and divide. These events can be controlled by the regulatory network, or by a database of recorded cell positions. In addition, the cells have a state composed of the presence and activity of all relevant regulatory molecules. The state can change cell-autonomously, i.e. based on the activity of the molecules within the cell, or as a result of intercellular interactions with molecules in neighboring cells. Because of the cell movement, cell-cell contacts change and with them, the possible interactions. This can lead to cell differentiation, i.e. the development of several different stable states from one or two initial states, a process that cannot be simulated with single-cell models.
Several example organisms and developmental processes were simulated with Gene-O-Matic, demonstrating its usefulness and functionality. One example is embryonic development of the worm Caenorhabditis elegans, which can be reproduced correctly by our simulations for more than 50 minutes, corresponding to 12 cells and 7 different cell types. This is the first time such a complex developmental process has been simulated successfully. By modifying the regulatory network, the phenotype of mutants can also be reproduced accurately. Other biological processes explored using Gene-O-Matic include flower development in Arabidopsis thaliana, and mating in Saccharomcyes cerevisiae (baker's yeast).
Gene-O-Matic already contains differrent simulation methods for the regulatory network. New methods can easily be included using a plugin mechanism. Also, new cell models can be added, for example to model cells with special growth or division behaviour, such as baker's yeast. Gene-O-Matic is an extensible simulation tool which has already proven its value in several simulations.
Gene-O-Matic is availabe on request from the authors, or by e-mail to cello@dkfz.de. The project's website can be found at http://mbi.dkfz-heidelberg.de/projects/cellsim/.