Modeling Biological Networks

IV.1 Coordinators
IV.2 Participants
IV.3 Introduction
IV.4 Background and Significance
IV.5 Research Plan
IV.6 Specific Subprojects
IV.7 Connection to Specific Projects 2 (cytoskeleton) and 3 (organogenesis)
IV.8 Timeline

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IV.8 TIMELINE:

Year I
Year II
Year III
Year IV
Year V

Year I

Subproject
1 and 2	Collect and organize database information pertaining to E coli and S. Cerevisiae metabolism and regulatory networks. Collect and organize microarray information for S. Cerevisiae and E. Coli.
3	Develop statistical methods and apply them to selected datasets.
4	Begin mathematical design of integrated model.
5	Begin developing sea urchin microarrays.
6	Design and manufacture a transcription factor microarray in collaboration with the DGRC.
7	Experiment: Testing of Xenopus KEH2 microarray. Collection of expression profile data from GATA-4 injected Xenopus animal caps and complete cardiogenic developmental timecourse. Modeling: Generation of Cardiogenic temporal profile.

     

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Year II

Subproject
1 and 2	Analyze the topological properties of the collected metabolic and regulatory graphs. Investigate the topological features of the cytoskeleton and information pathways, correlating the two groups of genes based on topological data.
3	Identify "candidate words" in the whole Drosophila genome. Begin analysis of correlations between words and between words and promoters.
4	Complete design of integrated model.
5	Produce sea urchin microarrays and begin analysis of gene expression patterns.
6	Analyze transcription factor changes in hormone-treated Kc cells and in cells misexpressing select transcription factors (e.g. EcR).
7	Experiment: Overexpression and Suppression of known cardiogenic transcription factors in Xenopus embryos - collection of RNA. Collection of expression profile data from the above experiments. Modeling: Development of initial theoretical cardiogenic transcriptional network model.

     

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Year III

Subproject
1 and 2	Develop tools to identify modules from topological data. Test and apply the developed methods on the metabolic and regulatory networks. Investigate the modularity of the regulatory network, and the overlap between modules, with particular emphasis to signaling and cytoskeletal proteins. Continue analysis of expression patterns. Create web-based database of patterns. Begin analysis of expression patterns in misexpression embryos. Analyze transcription factor changes in the metamorphosing Drosophila salivary gland.
3	Develop procedures to "map" clusters of words and begin large-scale mapping. Develop and implement a web-based interface.
4	Begin Computational implementation of integrated model.
5	Continue analysis of sea urchin gene expression patterns.
6	Begin Network analysis of Drosophila genome.
7	Experiment: Characterization of newly discovered genes. Testing of network model through additional profiling experiments. Modeling: Validation and modification of cardiogenic transcriptional network model.

     

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Year IV

Subproject	Dynamics of cellular networks; Experimental Validation
1 and 2	Develop tools to analyze the dynamical properties of regulatory networks using flux balance analysis and microarray data. Uncover genetic networks from dynamical data (microarrays).
3	Relate the maps to the genome annotation and refine the web database.
4	Develop integrated models of cellular networks, assembling together topological and dynamical information.
5	Experiment: Characterization of newly discovered genes. Testing of network model through additional profiling experiments. Modeling: Continued validation and modification of cardiogenic transcriptional network model.

     

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Year V

Subproject	Correlating topology and dynamics.
1 and 2	Identify modular information by analyzing jointly the regulatory topology and the microarray data.
3	Test and validate the integrated model, using lethality information, as well as newly emerging data sets. Correlate modular and topological features with dynamics properties collected from microarray data. Include into the proposed model newly emerging information (e.g. from proteomics, regulon information, etc.).
4	Conclude Network analysis. Compare to Drosophila
5	Conclude Network analysis. Compare to other genomes.
6	Experiment: In-depth characterization of particular cardiogenic pathways of interest. Possible exploration of outside tissue influence on cardiogenic network. Modeling: Public release of transcriptional network modeling software.