Genome Technology s Peer Review: A Weekly Forum of Recently Published Journal Articles: Mar 1, 2005

Following is a description of a recently published research paper recommended by a scientist involved in integrated biology. The recommender, Bud Mishra, is a professor of cell biology, computer science, and mathematics at New YorkUniversity.

For a complete list of recommended papers, read Genome Technology, a GenomeWeb News sister publication.

The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. Lee E, Salic A, Kruger R, Heinrich R, and Kirschner MW, PLoS Biol.1(1): 2003.

In work led by Marc Kirschner at HarvardMedicalSchool, the authors developed a mathematical model for the canonical Wnt pathway that describes the interactions among the core components: Wnt, Frizzled, Dishevelled, GSK3beta, APC, Axin, beta-catenin, and TCF. Using a system of differential equations, the model incorporates the kinetics of protein-protein interactions, protein synthesis/degradation, and phosphorylation/dephosphorylation. Predictions based on the analysis of the reference state were used iteratively to develop a more refined model that was used to analyze the effects of prolonged and transient Wnt stimulation on beta-catenin and Axin turnover. An insight from the model, confirmed experimentally, is that the two scaffold proteins Axin and APC promote the formation of degradation complexes in very different ways.

"This paper demonstrates concretely the power of a multidisciplinary approach and will become a forerunner of a framework that will be duplicated by others," said Bud Mishra, a computational biologist at New YorkUniversity. "The techniques that the researchers employed in the paper are based on ODE models, numerical integration, and direct comparison of numerical traces and time course data -- which can all be carried out with existing scientific computational tools -- but the work will influence, encourage, and inspire others to develop novel techniques to make better quantitative measurements and to rigorously analyze complex biological systems," he added.

Bud Mishra
Professor of Cell Biology, Computer Science, and Mathematics

New YorkUniversity