CAM colloquium - April 9 (Joint with IGERT Program in Nonlinear Systems)

Reka Albert
Physics Department
Penn State

"Modeling Gene Regulatory Networks"

Biological systems form complex networks of interaction on several scales, ranging from the molecular to the ecosystem level. On the subcellular scale, interaction between genes and gene products (mRNAs, proteins) forms the basis of essential processes like signal transduction, cell metabolism or embryonic development. Recent experimental advances helped uncover the qualitative structure of many gene control and metabolic networks, creating a surge of interest in the quantitative description of gene regulation. The theoretical progress proceeds along two complementary lines. First, the statistical description of network topology gives insights into the organizing principles of regulatory networks. Second, modeling the dynamics and function of well-characterized network modules leads to predictions that can be tested experimentally. I will focus on this second approach, presenting a model of the segment polarity genes of the fruit fly Drosophila melanogaster. These genes play an important role in the segmentation of the fruit fly embryo, and they are expressed in a stable striped pattern during a considerable part of Drosophila's embryonic development.

The basis of our model is the known interactions between the products of the segment polarity genes, and the network topology these interactions form. We then assume that mRNAs and proteins are either ON or OFF, and their interactions can be formulated as logical (Boolean) functions. Our model reproduces the experimentally observed expression patterns for wild-type, mutant or over-expressed genes. The success of this model suggests that the kinetic details of the interactions are not essential as long as the network of interactions is unperturbed. In addition, the model gives insights into the functioning of the network, suggesting a remarkable robustness towards changes in internal parameters, initial conditions and even some mutations, as long as some crucial conditions are met.