Vanderbilt medical center

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Merging signaling and math

by Mary Beth Gardiner

An ambitious collaborative program is emerging with the intent to mathematically model signal transduction and the way networks of signaling pathways impact cellular phenomena such as cell shape change and cell migration. The effort to bring quantitative approaches to biological problems is being led by a group of mathematicians headed by Emmanuele DiBenedetto, and combines the expertise of groups as diverse as mathematicians, computer scientists, biological scientists, and bioinformaticians.

These collaborations may grow into a cross-disciplinary, multi-institutional center pending the outcome of a proposal recently submitted to the NIH by Heidi Hamm and DiBenedetto. The center, to be called the Vanderbilt-Meharry Center of Excellence in Modeling Complex Signaling Networks, would facilitate interaction among scientists from Vanderbilt University and Meharry Medical College.

The major challenge, Hamm says, would be to “seamlessly integrate experimental data with theoretical and systematic modeling.” Computational bioinformatic techniques would be used to integrate information from multiple sources, including experimental data such as gene expression data, protein-protein interaction data, genomic sequence data, subcellular localization data, and lipidomics data. These data would feed into and enrich mathematical models of the process, which would then be used to design targeted experiments for study of specific pathway components.

The long-term goals of the proposed center are:
• to investigate the spatio-temporal dynamics of signal transduction through a single pathway, and subsequently through multiple pathways simultaneously engaged
• to visualize the dynamics of diffusion of aqueous and lipidic second messengers
• to develop mathematical and computer models of signal transduction through various signaling pathways
• to develop theoretical and computer research tools to model these signaling systems and to cross-validate
models and data

The center’s mission would also include a strong educational component with the aim of producing a new generation of students equally versed in wet-bench experimentation, theoretical elaborations, and computer implementations. The educational effort is already well underway, with the formation of the Biomath Study Group and a number of collaborative teams on campus modeling diverse aspects of signaling.

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