Systems biology of morphogen systems:
Much is known about the molecular components involved in signal transduction and gene expression in a number of model systems in developmental biology, and the focus is now shifting to understanding how these components are integrated into networks, and how these networks transduce the inputs they receive and produce the desired pattern of gene expression. The major question is how the correct genes are turned on at the correct point in space at the correct time in development to produce the numerous cell types present in an adult. While the problem is simply stated, delineating the mechanisms of development
that impart the robust control requires sophisticated computational models. For instance, consider the simple morphogen model as depicted in figure (A). The classic paradigm of a static morphogen distribution fails to explain a number of biological phenomena including scale-invariance (B), dynamic signaling response (C) and resilience to stochastic noice (D). To study these problems, we focus on coupling advanced microscopy and image analysis with multi-dimensional finite-element models of biological patterning mechanisms: most recently BMP patterning of Drosophila embryos. The direct incorporation of experimental data into geometrically accurate computational models leads to significant new biological insights that cannot be gained by either approach indepenently.